Alterations in Circulating Immune Cells in Neovascular Age-Related Macular Degeneration
Identifieur interne : 001525 ( Pmc/Checkpoint ); précédent : 001524; suivant : 001526Alterations in Circulating Immune Cells in Neovascular Age-Related Macular Degeneration
Auteurs : Judith Lechner [Royaume-Uni] ; Mei Chen [Royaume-Uni] ; Ruth E. Hogg [Royaume-Uni] ; Levente Toth [Royaume-Uni] ; Giuliana Silvestri [Royaume-Uni] ; Usha Chakravarthy [Royaume-Uni] ; Heping Xu [Royaume-Uni]Source :
- Scientific Reports [ 2045-2322 ] ; 2015.
Abstract
Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible blindness in developed countries. Recent advances have highlighted the essential role of inflammation in the development of the disease. In addition to local retinal chronic inflammatory response, systemic immune alterations have also been observed in AMD patients. In this study we investigated the association between the frequency of circulating leukocyte populations and the prevalence as well as clinical presentations of nAMD. Leukocyte subsets of 103 nAMD patients (most of them were receiving anti-VEGF therapy prior to enrolment) and 26 controls were analysed by flow cytometry by relative cell size, granularity and surface markers. Circulating CD11b+ cells and CD16hiHLA-DR− neutrophils were significantly increased (
Url:
DOI: 10.1038/srep16754
PubMed: 26572732
PubMed Central: 4648089
Affiliations:
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Hogg</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast</institution>, Belfast,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Toth, Levente" sort="Toth, Levente" uniqKey="Toth L" first="Levente" last="Toth">Levente Toth</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast</institution>, Belfast,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Silvestri, Giuliana" sort="Silvestri, Giuliana" uniqKey="Silvestri G" first="Giuliana" last="Silvestri">Giuliana Silvestri</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast</institution>, Belfast,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chakravarthy, Usha" sort="Chakravarthy, Usha" uniqKey="Chakravarthy U" first="Usha" last="Chakravarthy">Usha Chakravarthy</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast</institution>, Belfast,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Xu, Heping" sort="Xu, Heping" uniqKey="Xu H" first="Heping" last="Xu">Heping Xu</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast</institution>, Belfast,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible blindness in developed countries. Recent advances have highlighted the essential role of inflammation in the development of the disease. In addition to local retinal chronic inflammatory response, systemic immune alterations have also been observed in AMD patients. In this study we investigated the association between the frequency of circulating leukocyte populations and the prevalence as well as clinical presentations of nAMD. Leukocyte subsets of 103 nAMD patients (most of them were receiving anti-VEGF therapy prior to enrolment) and 26 controls were analysed by flow cytometry by relative cell size, granularity and surface markers. Circulating CD11b<sup>+</sup> cells and CD16<sup>hi</sup>HLA-DR<sup>−</sup> neutrophils were significantly increased (<italic>P </italic>= 0.015 and 0.009 respectively) in nAMD when compared to controls. The percentage of circulating CD4<sup>+</sup> T-cells was reduced in nAMD patients without subretinal fibrosis (<italic>P </italic>= 0.026) compared to patients with subretinal fibrosis. There was no correlation between the percentage of circulating leukocytes and the responsiveness to anti-VEGF therapy in nAMD patients. Our results suggest that higher levels of circulating CD11b<sup>+</sup> cells and neutrophils are associated with nAMD and that reduced levels of CD4<sup>+</sup> T-cells are associated with the absence of subretinal fibrosis in nAMD.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Klein, R" uniqKey="Klein R">R. Klein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bressler, N M" uniqKey="Bressler N">N. M. Bressler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Coleman, H R" uniqKey="Coleman H">H. R. Coleman</name></author><author><name sortKey="Chan, C C" uniqKey="Chan C">C. C. Chan</name></author><author><name sortKey="Ferris, F L" uniqKey="Ferris F">F. L. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id><journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id><journal-title-group><journal-title>Scientific Reports</journal-title></journal-title-group><issn pub-type="epub">2045-2322</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26572732</article-id><article-id pub-id-type="pmc">4648089</article-id><article-id pub-id-type="pii">srep16754</article-id><article-id pub-id-type="doi">10.1038/srep16754</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Alterations in Circulating Immune Cells in Neovascular Age-Related Macular Degeneration</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lechner</surname><given-names>Judith</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Mei</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hogg</surname><given-names>Ruth E.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Toth</surname><given-names>Levente</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Silvestri</surname><given-names>Giuliana</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chakravarthy</surname><given-names>Usha</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Xu</surname><given-names>Heping</given-names></name><xref ref-type="corresp" rid="c1">a</xref><xref ref-type="aff" rid="a1">1</xref></contrib><aff id="a1"><label>1</label><institution>Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast</institution>, Belfast,<country>UK</country></aff></contrib-group><author-notes><corresp id="c1"><label>a</label><email>heping.xu@qub.ac.uk</email></corresp></author-notes><pub-date pub-type="epub"><day>17</day><month>11</month><year>2015</year></pub-date><pub-date pub-type="collection"><year>2015</year></pub-date><volume>5</volume><elocation-id>16754</elocation-id><history><date date-type="received"><day>12</day><month>06</month><year>2015</year></date><date date-type="accepted"><day>20</day><month>10</month><year>2015</year></date></history><permissions><copyright-statement>Copyright © 2015, Macmillan Publishers Limited</copyright-statement><copyright-year>2015</copyright-year><copyright-holder>Macmillan Publishers Limited</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link></license-p></license></permissions><abstract><p>Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible blindness in developed countries. Recent advances have highlighted the essential role of inflammation in the development of the disease. In addition to local retinal chronic inflammatory response, systemic immune alterations have also been observed in AMD patients. In this study we investigated the association between the frequency of circulating leukocyte populations and the prevalence as well as clinical presentations of nAMD. Leukocyte subsets of 103 nAMD patients (most of them were receiving anti-VEGF therapy prior to enrolment) and 26 controls were analysed by flow cytometry by relative cell size, granularity and surface markers. Circulating CD11b<sup>+</sup> cells and CD16<sup>hi</sup>HLA-DR<sup>−</sup> neutrophils were significantly increased (<italic>P </italic>= 0.015 and 0.009 respectively) in nAMD when compared to controls. The percentage of circulating CD4<sup>+</sup> T-cells was reduced in nAMD patients without subretinal fibrosis (<italic>P </italic>= 0.026) compared to patients with subretinal fibrosis. There was no correlation between the percentage of circulating leukocytes and the responsiveness to anti-VEGF therapy in nAMD patients. Our results suggest that higher levels of circulating CD11b<sup>+</sup> cells and neutrophils are associated with nAMD and that reduced levels of CD4<sup>+</sup> T-cells are associated with the absence of subretinal fibrosis in nAMD.</p></abstract></article-meta></front><floats-group><fig id="f1"><label>Figure 1</label><caption><title>The relationship between the number of anti-VEGF injections and different subsets of circulating immune cells.</title><p>The number of anti-VEGF injections received by nAMD patients did not correlate with the percentage of lymphocytes <bold>(a)</bold>, neutrophils <bold>(b)</bold>, the NLR <bold>(c)</bold>, with the percentage of CD11b<sup>+</sup> cells <bold>(d)</bold>, CD16<sup>hi</sup>HLA-DR<sup>−</sup> neutrophils <bold>(e)</bold>, the CD16<sup>hi</sup>HLA-DR<sup>−</sup>/(CD4 + CD8) ratio <bold>(f)</bold> or the CD16<sup>hi</sup>HLA-DR<sup>−</sup>/CD8 ratio <bold>(g)</bold>.</p></caption><graphic xlink:href="srep16754-f1"></graphic></fig><fig id="f2"><label>Figure 2</label><caption><title>Gating strategy used in flow cytometry analysis to detect different subsets of circulating immune cells.</title><p>Sample data from a control (<bold>a</bold>–<bold>d</bold>,<bold>i</bold>,<bold>k</bold>) and a nAMD patient (<bold>e</bold>–<bold>h</bold>,<bold>j</bold>,l) are shown. Lymphocyte, monocyte and neutrophil populations were gated on a forward scatter (FSC)/side scatter (SSC) plot (<bold>a</bold>,<bold>e</bold>). Lymphocytes were then further gated to determine CD4<sup>+</sup>, CD8<sup>+</sup> (<bold>b,f</bold>), CD19<sup>+</sup> and CD56<sup>+</sup> lymphocytes (<bold>c</bold>,<bold>g</bold>). Live cells were further gated to determine CD11b<sup>+</sup> cells (<bold>d</bold>,<bold>h</bold>), CD14<sup>+</sup> monocytes (<bold>i,j)</bold> and CD16<sup>hi</sup>HLA-DR<sup>−</sup> neutrophils (<bold>k</bold>,<bold>l</bold>).</p></caption><graphic xlink:href="srep16754-f2"></graphic></fig><table-wrap position="float" id="t1"><label>Table 1</label><caption><title>Demographic and clinical characteristics of nAMD patients and controls.</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th><th align="center" valign="top" charoff="50"><bold>All (n</bold><italic> </italic>= <bold>129)</bold></th><th align="center" valign="top" charoff="50"><bold>Controls (n</bold><italic> </italic>= <bold>26)</bold></th><th align="center" valign="top" charoff="50"><bold>nAMD (n</bold><italic> </italic>= <bold>103)</bold></th><th align="center" valign="top" charoff="50"><italic><bold>P</bold></italic><bold>value nAMD vs Control</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">Age (median (range)), years</td><td align="center" valign="top" charoff="50">79.1 (53–94)</td><td align="center" valign="top" charoff="50">76.7 (59–92)</td><td align="center" valign="top" charoff="50">79.5 (53–94)</td><td align="center" valign="top" charoff="50">0.065<xref ref-type="fn" rid="t1-fn1">1</xref></td></tr><tr><td align="left" valign="top" charoff="50">Female sex (number (%))</td><td align="center" valign="top" charoff="50">70 (54)</td><td align="center" valign="top" charoff="50">12 (46)</td><td align="center" valign="top" charoff="50">58 (56)</td><td align="center" valign="top" charoff="50">0.385<xref ref-type="fn" rid="t1-fn2">2</xref></td></tr><tr><td align="left" valign="top" charoff="50">Have history of AMD (number (%))</td><td align="center" valign="top" charoff="50">30 (23)</td><td align="center" valign="top" charoff="50">5 (19)</td><td align="center" valign="top" charoff="50">25 (24)</td><td align="center" valign="top" charoff="50">0.796<xref ref-type="fn" rid="t1-fn2">2</xref></td></tr><tr><td align="left" valign="top" charoff="50">Have history of cardiovascular disease (number (%))</td><td align="center" valign="top" charoff="50">29 (22)</td><td align="center" valign="top" charoff="50">7 (27)</td><td align="center" valign="top" charoff="50">22 (21)</td><td align="center" valign="top" charoff="50">0.601<xref ref-type="fn" rid="t1-fn2">2</xref></td></tr><tr><td align="left" valign="top" charoff="50">Have history of hypertension (number (%))</td><td align="center" valign="top" charoff="50">75 (58)</td><td align="center" valign="top" charoff="50">17 (65)</td><td align="center" valign="top" charoff="50">58 (56)</td><td align="center" valign="top" charoff="50">0.506<xref ref-type="fn" rid="t1-fn2">2</xref></td></tr><tr><td align="left" valign="top" charoff="50">Have history of diabetes (number (%))</td><td align="center" valign="top" charoff="50">15 (12)</td><td align="center" valign="top" charoff="50">2 (8)</td><td align="center" valign="top" charoff="50">13 (13)</td><td align="center" valign="top" charoff="50">0.734<xref ref-type="fn" rid="t1-fn2">2</xref></td></tr><tr><td align="left" valign="top" charoff="50">Body Mass Index (mean ± SD)</td><td align="center" valign="top" charoff="50">26.4 (4.9)</td><td align="center" valign="top" charoff="50">27.1 (5.6)</td><td align="center" valign="top" charoff="50">26.1 (4.7)</td><td align="center" valign="top" charoff="50">0.397<xref ref-type="fn" rid="t1-fn3">3</xref></td></tr><tr><td align="left" valign="top" charoff="50">Smoking status</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">0.633<xref ref-type="fn" rid="t1-fn2">2</xref></td></tr><tr><td align="left" valign="top" charoff="50">Non-smoker (number (%))</td><td align="center" valign="top" charoff="50">52 (40)</td><td align="center" valign="top" charoff="50">11 (42)</td><td align="center" valign="top" charoff="50">41 (40)</td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50">Former smoker (number (%))</td><td align="center" valign="top" charoff="50">66 (51)</td><td align="center" valign="top" charoff="50">14 (54)</td><td align="center" valign="top" charoff="50">52 (50)</td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50">Current smoker (number (%))</td><td align="center" valign="top" charoff="50">11 (9)</td><td align="center" valign="top" charoff="50">1 (4)</td><td align="center" valign="top" charoff="50">10 (10)</td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50">Taking cardiovascular medication (number (%))</td><td align="center" valign="top" charoff="50">90 (87)</td><td align="center" valign="top" charoff="50">19 (73)</td><td align="center" valign="top" charoff="50">71 (69)</td><td align="center" valign="top" charoff="50">0.813<xref ref-type="fn" rid="t1-fn2">2</xref></td></tr><tr><td align="left" valign="top" charoff="50">Taking vitamins (number (%))</td><td align="center" valign="top" charoff="50">25 (19)</td><td align="center" valign="top" charoff="50">2 (8)</td><td align="center" valign="top" charoff="50">23 (22)</td><td align="center" valign="top" charoff="50">0.104<xref ref-type="fn" rid="t1-fn2">2</xref></td></tr><tr><td align="left" valign="top" charoff="50">Taking low-dose aspirin (number (%))</td><td align="center" valign="top" charoff="50">41(32)</td><td align="center" valign="top" charoff="50">4 (15)</td><td align="center" valign="top" charoff="50">37 (36)</td><td align="center" valign="top" charoff="50">0.059<xref ref-type="fn" rid="t1-fn2">2</xref></td></tr></tbody></table><table-wrap-foot><fn id="t1-fn1"><p>SD: Standard deviation.</p></fn><fn id="t1-fn2"><p><sup>1</sup>Mann Whitney U test.</p></fn><fn id="t1-fn3"><p><sup>2</sup>Pearson’s chi-square test.</p></fn><fn id="t1-fn4"><p><sup>3</sup>Independent samples t-test.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t2"><label>Table 2</label><caption><title>Percentage of leukocyte populations and cell ratios in nAMD patients and controls.</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th rowspan="2" align="left" valign="bottom" charoff="50"><bold>Variables</bold></th><th rowspan="2" align="center" valign="bottom" charoff="50"><bold>Controls (mean</bold> ± <bold>SD) n</bold><italic> </italic>= <bold>26</bold></th><th rowspan="2" align="center" valign="bottom" charoff="50"><bold>nAMD (mean</bold> ± <bold>SD) n</bold><italic> </italic>= <bold>103</bold></th><th align="center" valign="top" charoff="50"><bold>Univariate analysis</bold></th><th colspan="3" align="left" valign="top" charoff="50"><bold>Multivariate analysis (age and gender)</bold></th><th colspan="3" align="left" valign="top" charoff="50"><bold>Multivariate analysis (age, gender, cardiovascular disease and aspirin intake)</bold></th></tr><tr><th align="center" valign="top" charoff="50"><italic><bold>P</bold></italic><bold>value nAMD vs Controls</bold><sup>1</sup></th><th align="center" valign="top" charoff="50"><italic><bold>P</bold></italic><bold>value nAMD vs Controls</bold><xref ref-type="fn" rid="t2-fn2">2</xref></th><th align="center" valign="top" charoff="50"><bold>Odds ratio</bold></th><th align="center" valign="top" charoff="50"><bold>95% confidence interval for odds ratio</bold></th><th align="center" valign="top" charoff="50"><italic><bold>P</bold></italic><bold>value nAMD vs Controls</bold><xref ref-type="fn" rid="t2-fn3">3</xref></th><th align="center" valign="top" charoff="50"><bold>Odds ratio</bold></th><th align="center" valign="top" charoff="50"><bold>95% confidence interval for odds ratio</bold></th></tr></thead><tbody valign="top"><tr><td colspan="10" align="left" valign="top" charoff="50">Cell subsets (FSC/SSC plot)</td></tr><tr><td align="left" valign="top" charoff="50"> Lymphocytes (%)</td><td align="center" valign="top" charoff="50">30.45 ± 7.82</td><td align="center" valign="top" charoff="50">26.51 ± 6.97</td><td align="center" valign="top" charoff="50"><bold>0.013</bold></td><td align="center" valign="top" charoff="50"><bold>0.033</bold></td><td align="center" valign="top" charoff="50">0.94</td><td align="center" valign="top" charoff="50">0.88–0.99</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Monocytes (%)</td><td align="center" valign="top" charoff="50">7.28 ± 1.88</td><td align="center" valign="top" charoff="50">7.85 ± 2.58</td><td align="center" valign="top" charoff="50">0.292</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Neutrophils (%)</td><td align="center" valign="top" charoff="50">59.80 ± 8.73</td><td align="center" valign="top" charoff="50">63.71 ± 7.60</td><td align="center" valign="top" charoff="50"><bold>0.025</bold></td><td align="center" valign="top" charoff="50">0.052</td><td align="center" valign="top" charoff="50">1.06</td><td align="center" valign="top" charoff="50">1.00–1.12</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Neutrophil/Lymphocyte ratio</td><td align="center" valign="top" charoff="50">2.16 ± 0.84</td><td align="center" valign="top" charoff="50">2.66 ± 1.08</td><td align="center" valign="top" charoff="50"><bold>0.016</bold></td><td align="center" valign="top" charoff="50"><bold>0.037</bold></td><td align="center" valign="top" charoff="50">17.56</td><td align="center" valign="top" charoff="50">1.19–258.21</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td colspan="10" align="left" valign="top" charoff="50">Cell subsets (CD antigens)</td></tr><tr><td align="left" valign="top" charoff="50"> CD14<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">7.35 ± 1.95</td><td align="center" valign="top" charoff="50">7.61 ± 2.24</td><td align="center" valign="top" charoff="50">0.628</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD4<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">12.21 ± 3.92</td><td align="center" valign="top" charoff="50">11.46 ± 4.25</td><td align="center" valign="top" charoff="50">0.301</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD8<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">5.86 ± 2.96</td><td align="center" valign="top" charoff="50">5.06 ± 3.49</td><td align="center" valign="top" charoff="50">0.137</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD19<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">3.41 ± 2.16</td><td align="center" valign="top" charoff="50">2.78 ± 1.48</td><td align="center" valign="top" charoff="50">0.126</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD56<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">3.27 ± 1.66</td><td align="center" valign="top" charoff="50">3.46 ± 1.94</td><td align="center" valign="top" charoff="50">0.834</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD11b<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">67.40 ± 9.00</td><td align="center" valign="top" charoff="50">72.77 ± 7.68</td><td align="center" valign="top" charoff="50"><bold>0.006</bold></td><td align="center" valign="top" charoff="50"><bold>0.015</bold></td><td align="center" valign="top" charoff="50">1.08</td><td align="center" valign="top" charoff="50">1.01–1.14</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup> Neutrophils (%)</td><td align="center" valign="top" charoff="50">57.80 ± 9.05</td><td align="center" valign="top" charoff="50">63.19 ± 7.87</td><td align="center" valign="top" charoff="50"><bold>0.003</bold></td><td align="center" valign="top" charoff="50"><bold>0.009</bold></td><td align="center" valign="top" charoff="50">1.07</td><td align="center" valign="top" charoff="50">1.02–1.13</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/(CD4 + CD8) ratio</td><td align="center" valign="top" charoff="50">3.51 ± 1.49</td><td align="center" valign="top" charoff="50">4.42 ± 1.88</td><td align="center" valign="top" charoff="50"><bold>0.031</bold></td><td align="center" valign="top" charoff="50">0.072</td><td align="center" valign="top" charoff="50">10.24</td><td align="center" valign="top" charoff="50">0.81–129.24</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/CD4 ratio</td><td align="center" valign="top" charoff="50">5.34 ± 2.34</td><td align="center" valign="top" charoff="50">6.34 ± 2.74</td><td align="center" valign="top" charoff="50">0.100</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/CD8 ratio</td><td align="center" valign="top" charoff="50">13.80 ± 11.28</td><td align="center" valign="top" charoff="50">19.82 ± 16.22</td><td align="center" valign="top" charoff="50">0.051</td><td align="center" valign="top" charoff="50">0.072</td><td align="center" valign="top" charoff="50">3.97</td><td align="center" valign="top" charoff="50">0.88–17.88</td><td align="center" valign="top" charoff="50"><bold>0.041</bold></td><td align="center" valign="top" charoff="50">5.66</td><td align="center" valign="top" charoff="50">1.07–29.79</td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/CD19 ratio</td><td align="center" valign="top" charoff="50">25.69 ± 21.26</td><td align="center" valign="top" charoff="50">32.14 ± 26.91</td><td align="center" valign="top" charoff="50">0.085</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/CD56 ratio</td><td align="center" valign="top" charoff="50">22.41 ± 11.25</td><td align="center" valign="top" charoff="50">25.75 ± 19.89</td><td align="center" valign="top" charoff="50">0.714</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr></tbody></table><table-wrap-foot><fn id="t2-fn1"><p><bold>Bold</bold><italic>P</italic><0.05; SD: Standard deviation.</p></fn><fn id="t2-fn2"><p><sup>1</sup>Independent samples t-test.</p></fn><fn id="t2-fn3"><p><sup>2</sup>Multivariable logistic regression; corrected for age and gender.</p></fn><fn id="t2-fn4"><p><sup>3</sup>Multivariable logistic regression; corrected for age, gender, cardiovascular disease and aspirin intake.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t3"><label>Table 3</label><caption><title>Percentage of leukocyte populations and cell ratios in patients with nAMD with and without subretinal fibrosis.</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th rowspan="2" align="left" valign="bottom" charoff="50"><bold>Variables</bold></th><th rowspan="2" align="center" valign="bottom" charoff="50"><bold>Controls (mean</bold> ± <bold>SD) n</bold><italic> </italic>= <bold>26</bold></th><th rowspan="2" align="center" valign="bottom" charoff="50"><bold>Fibrosis absent (mean</bold> ± <bold>SD) n</bold><italic> </italic>= <bold>66</bold></th><th rowspan="2" align="center" valign="bottom" charoff="50"><bold>Fibrosis present (mean</bold> ± <bold>SD) n</bold><italic> </italic>= <bold>37</bold></th><th align="center" valign="top" charoff="50"><bold>Univariate analysis</bold></th><th colspan="3" align="center" valign="top" charoff="50"><bold>Multivariate analysis (age and gender)</bold></th></tr><tr><th align="center" valign="top" charoff="50"><italic><bold>P</bold></italic><bold>value fibrosis absent vs present</bold><xref ref-type="fn" rid="t3-fn1">1</xref></th><th align="center" valign="top" charoff="50"><italic><bold>P</bold></italic><bold>value fibrosis absent vs present</bold><xref ref-type="fn" rid="t3-fn2">2</xref></th><th align="center" valign="top" charoff="50"><bold>Odds ratio</bold></th><th align="center" valign="top" charoff="50"><bold>95% confidence interval for odds ratio</bold></th></tr></thead><tbody valign="top"><tr><td colspan="8" align="left" valign="top" charoff="50">Cell subsets (FSC/SSC plot)</td></tr><tr><td align="left" valign="top" charoff="50"> Lymphocytes (%)</td><td align="center" valign="top" charoff="50">30.45 ± 7.82</td><td align="center" valign="top" charoff="50">26.17 ± 7.4</td><td align="center" valign="top" charoff="50">27.11 ± 6.19</td><td align="center" valign="top" charoff="50">0.517</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Monocytes (%)</td><td align="center" valign="top" charoff="50">7.28 ± 1.88</td><td align="center" valign="top" charoff="50">8.09 ± 2.71</td><td align="center" valign="top" charoff="50">7.43 ± 2.32</td><td align="center" valign="top" charoff="50">0.215</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Neutrophils (%)</td><td align="center" valign="top" charoff="50">59.80 ± 8.73</td><td align="center" valign="top" charoff="50">63.80 ± 8.25</td><td align="center" valign="top" charoff="50">63.55 ± 6.37</td><td align="center" valign="top" charoff="50">0.869</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Neutrophil/Lymphocyte ratio</td><td align="center" valign="top" charoff="50">2.16 ± 0.84</td><td align="center" valign="top" charoff="50">2.75 ± 1.22</td><td align="center" valign="top" charoff="50">2.51 ± 0.77</td><td align="center" valign="top" charoff="50">0.515</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td colspan="8" align="left" valign="top" charoff="50">Cell subsets (CD antigens)</td></tr><tr><td align="left" valign="top" charoff="50"> CD14<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">7.35 ± 1.95</td><td align="center" valign="top" charoff="50">7.75 ± 2.39</td><td align="center" valign="top" charoff="50">7.35 ± 1.96</td><td align="center" valign="top" charoff="50">0.447</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD4<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">12.21 ± 3.92</td><td align="center" valign="top" charoff="50">10.82 ± 4.08</td><td align="center" valign="top" charoff="50">12.44 ± 4.37</td><td align="center" valign="top" charoff="50"><bold>0.042</bold></td><td align="center" valign="top" charoff="50"><bold>0.026</bold></td><td align="center" valign="top" charoff="50">37.08</td><td align="center" valign="top" charoff="50">1.53–899.43</td></tr><tr><td align="left" valign="top" charoff="50"> CD8<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">5.86 ± 2.96</td><td align="center" valign="top" charoff="50">5.39 ± 3.8</td><td align="center" valign="top" charoff="50">4.51 ± 2.85</td><td align="center" valign="top" charoff="50">0.326</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD19<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">3.41 ± 2.16</td><td align="center" valign="top" charoff="50">2.95 ± 1.69</td><td align="center" valign="top" charoff="50">2.53 ± 1.07</td><td align="center" valign="top" charoff="50">0.249</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD56<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">3.27 ± 1.66</td><td align="center" valign="top" charoff="50">3.49 ± 1.57</td><td align="center" valign="top" charoff="50">3.42 ± 2.34</td><td align="center" valign="top" charoff="50">0.340</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD11b<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">67.40 ± 9.00</td><td align="center" valign="top" charoff="50">72.97 ± 8.47</td><td align="center" valign="top" charoff="50">72.48 ± 6.55</td><td align="center" valign="top" charoff="50">0.797</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup> Neutrophils (%)</td><td align="center" valign="top" charoff="50">57.80 ± 9.05</td><td align="center" valign="top" charoff="50">63.33 ± 8.7</td><td align="center" valign="top" charoff="50">62.95 ± 6.21</td><td align="center" valign="top" charoff="50">0.798</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/(CD4 + CD8) ratio</td><td align="center" valign="top" charoff="50">3.51 ± 1.49</td><td align="center" valign="top" charoff="50">4.60 ± 2.06</td><td align="center" valign="top" charoff="50">4.13 ± 1.56</td><td align="center" valign="top" charoff="50">0.462</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/CD4 ratio</td><td align="center" valign="top" charoff="50">5.34 ± 2.34</td><td align="center" valign="top" charoff="50">6.80 ± 3.07</td><td align="center" valign="top" charoff="50">5.65 ± 1.97</td><td align="center" valign="top" charoff="50">0.120</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/CD8 ratio</td><td align="center" valign="top" charoff="50">13.80 ± 11.28</td><td align="center" valign="top" charoff="50">19.10 ± 15.52</td><td align="center" valign="top" charoff="50">21.02 ± 17.48</td><td align="center" valign="top" charoff="50">0.381</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/CD19 ratio</td><td align="center" valign="top" charoff="50">25.69 ± 21.26</td><td align="center" valign="top" charoff="50">31.16 ± 27.45</td><td align="center" valign="top" charoff="50">33.55 ± 26.44</td><td align="center" valign="top" charoff="50">0.354</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/CD56 ratio</td><td align="center" valign="top" charoff="50">22.41 ± 11.25</td><td align="center" valign="top" charoff="50">22.91 ± 15.72</td><td align="center" valign="top" charoff="50">29.25 ± 23.86</td><td align="center" valign="top" charoff="50">0.274</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr></tbody></table><table-wrap-foot><fn id="t3-fn1"><p><bold>Bold</bold> P < 0.05; SD: Standard deviation.</p></fn><fn id="t3-fn2"><p><sup>1</sup>Independent samples t-test.</p></fn><fn id="t3-fn3"><p><sup>2</sup>Multivariable logistic regression; corrected for age and gender.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t4"><label>Table 4</label><caption><title>Percentage of leukocyte populations and cell ratios in nAMD patients with CNV and RAP.</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th><th align="center" valign="top" charoff="50"> </th><th align="center" valign="top" charoff="50"> </th><th align="center" valign="top" charoff="50"> </th><th colspan="3" align="center" valign="top" charoff="50"><bold>Univariate analysis</bold></th><th colspan="3" align="center" valign="top" charoff="50"><bold>Multivariate analysis (age and gender)</bold></th></tr><tr><th align="left" valign="top" charoff="50"><bold>Variables</bold></th><th align="center" valign="top" charoff="50"><bold>Controls (mean</bold> ± <bold>SD) n</bold><italic> </italic>= <bold>26</bold></th><th align="center" valign="top" charoff="50"><bold>CNV (mean</bold> ± <bold>SD) n</bold><italic> </italic>= <bold>66</bold></th><th align="center" valign="top" charoff="50"><bold>RAP (mean</bold> ± <bold>SD) n</bold><italic> </italic>= <bold>13</bold></th><th align="center" valign="top" charoff="50"><italic><bold>P</bold></italic><bold>value CNV vs RAP</bold><xref ref-type="fn" rid="t4-fn1">1</xref></th><th align="center" valign="top" charoff="50"><italic><bold>P</bold></italic><bold>value CNV vs RAP vs controls</bold><xref ref-type="fn" rid="t4-fn2">2</xref></th><th align="center" valign="top" charoff="50"><italic><bold>P</bold></italic><bold>value Bonferroni</bold><italic><bold>post hoc</bold></italic><bold>test</bold></th><th align="center" valign="top" charoff="50"><italic><bold>P</bold></italic><bold>value CNV vs RAP vs controls</bold><xref ref-type="fn" rid="t4-fn3">3</xref></th><th align="center" valign="top" charoff="50"><bold>Odds ratio</bold></th><th align="center" valign="top" charoff="50"><bold>95% confidence interval for odds ratio</bold></th></tr></thead><tbody valign="top"><tr><td colspan="10" align="left" valign="top" charoff="50">Cell subsets (FSC/SSC plot)</td></tr><tr><td align="left" valign="top" charoff="50"> Lymphocytes (%)</td><td align="center" valign="top" charoff="50">30.45 ± 7.82</td><td align="center" valign="top" charoff="50">27.13 ± 7.32</td><td align="center" valign="top" charoff="50">24.62 ± 6.36</td><td align="center" valign="top" charoff="50">0.254</td><td align="center" valign="top" charoff="50"><bold>0.047</bold></td><td align="center" valign="top" charoff="50">0.161<xref ref-type="fn" rid="t4-fn5">4</xref> 0.064<xref ref-type="fn" rid="t4-fn6">5</xref></td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Monocytes (%)</td><td align="center" valign="top" charoff="50">7.28 ± 1.88</td><td align="center" valign="top" charoff="50">7.84 ± 2.38</td><td align="center" valign="top" charoff="50">8.44 ± 4.02</td><td align="center" valign="top" charoff="50">0.468</td><td align="center" valign="top" charoff="50">0.382</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Neutrophils (%)</td><td align="center" valign="top" charoff="50">59.80 ± 8.73</td><td align="center" valign="top" charoff="50">63.28 ± 7.55</td><td align="center" valign="top" charoff="50">65.35 ± 8.01</td><td align="center" valign="top" charoff="50">0.373</td><td align="center" valign="top" charoff="50">0.075</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Neutrophil/Lymphocyte ratio</td><td align="center" valign="top" charoff="50">2.16 ± 0.84</td><td align="center" valign="top" charoff="50">2.62 ± 1.17</td><td align="center" valign="top" charoff="50">2.87 ± 0.96</td><td align="center" valign="top" charoff="50">0.329</td><td align="center" valign="top" charoff="50">0.055</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td colspan="10" align="left" valign="top" charoff="50">Cell subsets (CD antigens)</td></tr><tr><td align="left" valign="top" charoff="50"> CD14<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">7.35 ± 1.95</td><td align="center" valign="top" charoff="50">7.61 ± 2.05</td><td align="center" valign="top" charoff="50">8.45 ± 3.57</td><td align="center" valign="top" charoff="50">0.336</td><td align="center" valign="top" charoff="50">0.472</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD4<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">12.21 ± 3.92</td><td align="center" valign="top" charoff="50">11.88 ± 4.75</td><td align="center" valign="top" charoff="50">10.77 ± 3.02</td><td align="center" valign="top" charoff="50">0.600</td><td align="center" valign="top" charoff="50">0.614</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD8<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">5.86 ± 2.96</td><td align="center" valign="top" charoff="50">5.25 ± 3.66</td><td align="center" valign="top" charoff="50">4.69 ± 2.49</td><td align="center" valign="top" charoff="50">0.978</td><td align="center" valign="top" charoff="50">0.425</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD19<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">3.41 ± 2.16</td><td align="center" valign="top" charoff="50">2.86 ± 1.37</td><td align="center" valign="top" charoff="50">2.19 ± 1.23</td><td align="center" valign="top" charoff="50">0.117</td><td align="center" valign="top" charoff="50">0.110</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD56<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">3.27 ± 1.66</td><td align="center" valign="top" charoff="50">3.50 ± 2.16</td><td align="center" valign="top" charoff="50">3.39 ± 1.71</td><td align="center" valign="top" charoff="50">0.801</td><td align="center" valign="top" charoff="50">0.958</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD11b<sup>+</sup> (%)</td><td align="center" valign="top" charoff="50">67.40 ± 9.00</td><td align="center" valign="top" charoff="50">72.00 ± 7.92</td><td align="center" valign="top" charoff="50">76.72 ± 5.42</td><td align="center" valign="top" charoff="50">0.082</td><td align="center" valign="top" charoff="50"><bold>0.007</bold></td><td align="center" valign="top" charoff="50">0.086<xref ref-type="fn" rid="t4-fn5">4</xref><bold>0.009</bold><xref ref-type="fn" rid="t4-fn6">5</xref></td><td align="center" valign="top" charoff="50"><bold>0.046</bold><xref ref-type="fn" rid="t4-fn5">4</xref><bold>0.033</bold><xref ref-type="fn" rid="t4-fn6">5</xref></td><td align="center" valign="top" charoff="50">1.07 1.15</td><td align="center" valign="top" charoff="50">1.00 ± 1.14 1.01 ± 1.30</td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup> Neutrophils (%)</td><td align="center" valign="top" charoff="50">57.80 ± 9.05</td><td align="center" valign="top" charoff="50">62.92 ± 8.09</td><td align="center" valign="top" charoff="50">63.26 ± 7.77</td><td align="center" valign="top" charoff="50">0.888</td><td align="center" valign="top" charoff="50"><bold>0.025</bold></td><td align="center" valign="top" charoff="50"><bold>0.027</bold><xref ref-type="fn" rid="t4-fn5">4</xref> 0.166<xref ref-type="fn" rid="t4-fn6">5</xref></td><td align="center" valign="top" charoff="50"><bold>0.015</bold><xref ref-type="fn" rid="t4-fn5">4</xref> 0.304<xref ref-type="fn" rid="t4-fn6">5</xref></td><td align="center" valign="top" charoff="50">1.08 1.05</td><td align="center" valign="top" charoff="50">1.01 ± 1.14 0.96 ± 1.15</td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/(CD4 + CD8) ratio</td><td align="center" valign="top" charoff="50">3.51 ± 1.49</td><td align="center" valign="top" charoff="50">4.25 ± 1.92</td><td align="center" valign="top" charoff="50">4.51 ± 1.56</td><td align="center" valign="top" charoff="50">0.487</td><td align="center" valign="top" charoff="50">0.150</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/CD4 ratio</td><td align="center" valign="top" charoff="50">5.34 ± 2.34</td><td align="center" valign="top" charoff="50">6.26 ± 2.94</td><td align="center" valign="top" charoff="50">6.40 ± 2.16</td><td align="center" valign="top" charoff="50">0.595</td><td align="center" valign="top" charoff="50">0.317</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/CD8 ratio</td><td align="center" valign="top" charoff="50">13.80 ± 11.28</td><td align="center" valign="top" charoff="50">20.40 ± 18.82</td><td align="center" valign="top" charoff="50">17.00 ± 8.09</td><td align="center" valign="top" charoff="50">0.997</td><td align="center" valign="top" charoff="50">0.221</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/CD19 ratio</td><td align="center" valign="top" charoff="50">25.69 ± 21.26</td><td align="center" valign="top" charoff="50">31.21 ± 27.79</td><td align="center" valign="top" charoff="50">45.60 ± 40.21</td><td align="center" valign="top" charoff="50">0.131</td><td align="center" valign="top" charoff="50">0.083</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> CD16<sup>hi</sup>HLA-DR<sup>−</sup>/CD56 ratio</td><td align="center" valign="top" charoff="50">22.41 ± 11.25</td><td align="center" valign="top" charoff="50">27.33 ± 23.06</td><td align="center" valign="top" charoff="50">23.06 ± 10.91</td><td align="center" valign="top" charoff="50">0.942</td><td align="center" valign="top" charoff="50">0.922</td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr></tbody></table><table-wrap-foot><fn id="t4-fn1"><p><bold>Bold</bold><italic>P </italic>< 0.05; SD: Standard deviation.</p></fn><fn id="t4-fn2"><p><sup>1</sup>Independent samples t-test.</p></fn><fn id="t4-fn3"><p><sup>2</sup>One-way ANOVA.</p></fn><fn id="t4-fn4"><p><sup>3</sup>Multinomial logistic regression corrected for age and gender.</p></fn><fn id="t4-fn5"><p><sup>4</sup>Controls vs CNV.</p></fn><fn id="t4-fn6"><p><sup>5</sup>Controls vs RAP.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list><country><li>Royaume-Uni</li></country></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Lechner, Judith" sort="Lechner, Judith" uniqKey="Lechner J" first="Judith" last="Lechner">Judith Lechner</name></noRegion><name sortKey="Chakravarthy, Usha" sort="Chakravarthy, Usha" uniqKey="Chakravarthy U" first="Usha" last="Chakravarthy">Usha Chakravarthy</name><name sortKey="Chen, Mei" sort="Chen, Mei" uniqKey="Chen M" first="Mei" last="Chen">Mei Chen</name><name sortKey="Hogg, Ruth E" sort="Hogg, Ruth E" uniqKey="Hogg R" first="Ruth E." last="Hogg">Ruth E. Hogg</name><name sortKey="Silvestri, Giuliana" sort="Silvestri, Giuliana" uniqKey="Silvestri G" first="Giuliana" last="Silvestri">Giuliana Silvestri</name><name sortKey="Toth, Levente" sort="Toth, Levente" uniqKey="Toth L" first="Levente" last="Toth">Levente Toth</name><name sortKey="Xu, Heping" sort="Xu, Heping" uniqKey="Xu H" first="Heping" last="Xu">Heping Xu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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