Arthritis in Two Patients With Partial Recombination Activating Gene Deficiency
Identifieur interne : 000F56 ( Main/Exploration ); précédent : 000F55; suivant : 000F57Arthritis in Two Patients With Partial Recombination Activating Gene Deficiency
Auteurs : Kevin Y. Wu [États-Unis] ; Pooja Purswani [États-Unis] ; Boglarka Ujhazi [États-Unis] ; Krisztian Csomos [États-Unis] ; Mihailova Snezhina [Bulgarie] ; Naumova Elissaveta [Bulgarie] ; Stefan Stefanov [Bulgarie] ; Svetlana Sharapova [Biélorussie] ; Maryssa Ellison [États-Unis] ; Diana Milojevic [États-Unis] ; Sinisa Savic [Royaume-Uni] ; Ravishankar Sargur [Royaume-Uni] ; Jolan E. Walter [États-Unis]Source :
- Frontiers in Pediatrics [ 2296-2360 ] ; 2019.
Abstract
Autoimmunity is becoming an increasingly recognized complication in patients with primary immunodeficiencies (PIDs), including a variety of combined immune deficiencies such as Recombination Activating Gene (RAG) defects. The approach to treating autoimmunity in PID patients is complex, requiring a balance between immunosuppression and susceptibility to infection. Inflammatory arthritis is a feature of immune dysregulation in many PIDs, and the optimal treatment may differ from first line therapies that usually consist of disease-modifying anti rheumatic drugs (DMARDs). An example of mechanism-based therapy of arthritis in PID uses blockade of IL-6 signaling with tocilizumab for patients with STAT 3 gain-of-function (GOF) mutation and augmented IL-6 pathway. Herein, we describe two PID cases with arthritis who were found to have defects in RAG. One patient with refractory inflammatory arthritis experienced remarkable improvement in symptoms with tocilizumab therapy. Arthritis can be a clinical feature of immune dysregulation in RAG deficiency, and tocilizumab therapy has been suggested to have utility in treatment of arthritis in RAG deficiency.
Url:
DOI: 10.3389/fped.2019.00235
PubMed: 31334206
PubMed Central: 6625222
Affiliations:
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Wu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Pediatric Allergy and Immunology, Department of Pediatrics, University of South Florida</institution>,<addr-line>St. Petersburg, FL</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Purswani, Pooja" sort="Purswani, Pooja" uniqKey="Purswani P" first="Pooja" last="Purswani">Pooja Purswani</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Johns Hopkins All Children's Hospital Children's Research Institute</institution>,<addr-line>St. Petersburg, FL</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ujhazi, Boglarka" sort="Ujhazi, Boglarka" uniqKey="Ujhazi B" first="Boglarka" last="Ujhazi">Boglarka Ujhazi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Pediatric Allergy and Immunology, Department of Pediatrics, University of South Florida</institution>,<addr-line>St. Petersburg, FL</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Csomos, Krisztian" sort="Csomos, Krisztian" uniqKey="Csomos K" first="Krisztian" last="Csomos">Krisztian Csomos</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Pediatrics, University of South Florida</institution>,<addr-line>St. Petersburg, FL</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Snezhina, Mihailova" sort="Snezhina, Mihailova" uniqKey="Snezhina M" first="Mihailova" last="Snezhina">Mihailova Snezhina</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Department of Clinical Immunology, University Hospital Alexandrovska, Medical University</institution>,<addr-line>Sofia</addr-line>,<country>Bulgaria</country></nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Elissaveta, Naumova" sort="Elissaveta, Naumova" uniqKey="Elissaveta N" first="Naumova" last="Elissaveta">Naumova Elissaveta</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Department of Clinical Immunology, University Hospital Alexandrovska, Medical University</institution>,<addr-line>Sofia</addr-line>,<country>Bulgaria</country></nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Stefanov, Stefan" sort="Stefanov, Stefan" uniqKey="Stefanov S" first="Stefan" last="Stefanov">Stefan Stefanov</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Clinic of Rheumatology, Cardiology and Hematology, University Pediatric Hospital, Medical University</institution>,<addr-line>Sofia</addr-line>,<country>Bulgaria</country></nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sharapova, Svetlana" sort="Sharapova, Svetlana" uniqKey="Sharapova S" first="Svetlana" last="Sharapova">Svetlana Sharapova</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Belarusian Research Center for Pediatric Oncology</institution>,<addr-line>Minsk</addr-line>,<country>Belarus</country></nlm:aff><country xml:lang="fr">Biélorussie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ellison, Maryssa" sort="Ellison, Maryssa" uniqKey="Ellison M" first="Maryssa" last="Ellison">Maryssa Ellison</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Pediatric Allergy and Immunology, Department of Pediatrics, University of South Florida</institution>,<addr-line>St. Petersburg, FL</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Milojevic, Diana" sort="Milojevic, Diana" uniqKey="Milojevic D" first="Diana" last="Milojevic">Diana Milojevic</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Division of Rheumatology, Department of Medicine, Johns Hopkins All Children's Hospital</institution>,<addr-line>St. Petersburg, FL</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Savic, Sinisa" sort="Savic, Sinisa" uniqKey="Savic S" first="Sinisa" last="Savic">Sinisa Savic</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Department of Clinical Immunology and Allergy, Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James's University Hospital</institution>,<addr-line>Leeds</addr-line>,<country>United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sargur, Ravishankar" sort="Sargur, Ravishankar" uniqKey="Sargur R" first="Ravishankar" last="Sargur">Ravishankar Sargur</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Department of Clinical Immunology and Allergy, Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James's University Hospital</institution>,<addr-line>Leeds</addr-line>,<country>United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff9"><institution>Sheffield Teaching Hospitals Foundation NHS Trust</institution>,<addr-line>Leeds</addr-line>,<country>United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Walter, Jolan E" sort="Walter, Jolan E" uniqKey="Walter J" first="Jolan E." last="Walter">Jolan E. Walter</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Pediatric Allergy and Immunology, Department of Pediatrics, University of South Florida</institution>,<addr-line>St. Petersburg, FL</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Johns Hopkins All Children's Hospital Children's Research Institute</institution>,<addr-line>St. Petersburg, FL</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Pediatrics</title><idno type="eISSN">2296-2360</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Autoimmunity is becoming an increasingly recognized complication in patients with primary immunodeficiencies (PIDs), including a variety of combined immune deficiencies such as Recombination Activating Gene (RAG) defects. The approach to treating autoimmunity in PID patients is complex, requiring a balance between immunosuppression and susceptibility to infection. Inflammatory arthritis is a feature of immune dysregulation in many PIDs, and the optimal treatment may differ from first line therapies that usually consist of disease-modifying anti rheumatic drugs (DMARDs). An example of mechanism-based therapy of arthritis in PID uses blockade of IL-6 signaling with tocilizumab for patients with STAT 3 gain-of-function (GOF) mutation and augmented IL-6 pathway. Herein, we describe two PID cases with arthritis who were found to have defects in RAG. One patient with refractory inflammatory arthritis experienced remarkable improvement in symptoms with tocilizumab therapy. Arthritis can be a clinical feature of immune dysregulation in RAG deficiency, and tocilizumab therapy has been suggested to have utility in treatment of arthritis in RAG deficiency.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Singh, Ja" uniqKey="Singh J">JA Singh</name></author><author><name sortKey="Saag, Kg" uniqKey="Saag K">KG Saag</name></author><author><name sortKey="Bridges, Sl Jr" uniqKey="Bridges S">SL Jr Bridges</name></author><author><name sortKey="Akl, Ea" uniqKey="Akl E">EA Akl</name></author><author><name sortKey="Bannuru, Rr" uniqKey="Bannuru R">RR Bannuru</name></author><author><name sortKey="Sullivan, Mc" uniqKey="Sullivan M">MC Sullivan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ringold, S" uniqKey="Ringold S">S Ringold</name></author><author><name sortKey="Weiss, Pf" uniqKey="Weiss P">PF Weiss</name></author><author><name sortKey="Beukelman, T" uniqKey="Beukelman T">T 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Rowe</name></author><author><name sortKey="Stadinski, Bd" uniqKey="Stadinski B">BD Stadinski</name></author><author><name sortKey="Henderson, La" uniqKey="Henderson L">LA Henderson</name></author><author><name sortKey="Ott De Bruin, L" uniqKey="Ott De Bruin L">L Ott de Bruin</name></author><author><name sortKey="Delmonte, O" uniqKey="Delmonte O">O Delmonte</name></author><author><name sortKey="Lee, Y" uniqKey="Lee Y">Y Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Henderson, La" uniqKey="Henderson L">LA Henderson</name></author><author><name sortKey="Volpi, S" uniqKey="Volpi S">S Volpi</name></author><author><name sortKey="Frugoni, F" uniqKey="Frugoni F">F Frugoni</name></author><author><name sortKey="Janssen, E" uniqKey="Janssen E">E Janssen</name></author><author><name sortKey="Kim, S" uniqKey="Kim S">S Kim</name></author><author><name sortKey="Sundel, R" uniqKey="Sundel R">R Sundel</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Biélorussie</li><li>Bulgarie</li><li>Royaume-Uni</li><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Wu, Kevin Y" sort="Wu, Kevin Y" uniqKey="Wu K" first="Kevin Y." last="Wu">Kevin Y. Wu</name></noRegion><name sortKey="Csomos, Krisztian" sort="Csomos, Krisztian" uniqKey="Csomos K" first="Krisztian" last="Csomos">Krisztian Csomos</name><name sortKey="Ellison, Maryssa" sort="Ellison, Maryssa" uniqKey="Ellison M" first="Maryssa" last="Ellison">Maryssa Ellison</name><name sortKey="Milojevic, Diana" sort="Milojevic, Diana" uniqKey="Milojevic D" first="Diana" last="Milojevic">Diana Milojevic</name><name sortKey="Purswani, Pooja" sort="Purswani, Pooja" uniqKey="Purswani P" first="Pooja" last="Purswani">Pooja Purswani</name><name sortKey="Ujhazi, Boglarka" sort="Ujhazi, Boglarka" uniqKey="Ujhazi B" first="Boglarka" last="Ujhazi">Boglarka Ujhazi</name><name sortKey="Walter, Jolan E" sort="Walter, Jolan E" uniqKey="Walter J" first="Jolan E." last="Walter">Jolan E. Walter</name><name sortKey="Walter, Jolan E" sort="Walter, Jolan E" uniqKey="Walter J" first="Jolan E." last="Walter">Jolan E. Walter</name></country><country name="Bulgarie"><noRegion><name sortKey="Snezhina, Mihailova" sort="Snezhina, Mihailova" uniqKey="Snezhina M" first="Mihailova" last="Snezhina">Mihailova Snezhina</name></noRegion><name sortKey="Elissaveta, Naumova" sort="Elissaveta, Naumova" uniqKey="Elissaveta N" first="Naumova" last="Elissaveta">Naumova Elissaveta</name><name sortKey="Stefanov, Stefan" sort="Stefanov, Stefan" uniqKey="Stefanov S" first="Stefan" last="Stefanov">Stefan Stefanov</name></country><country name="Biélorussie"><noRegion><name sortKey="Sharapova, Svetlana" sort="Sharapova, Svetlana" uniqKey="Sharapova S" first="Svetlana" last="Sharapova">Svetlana Sharapova</name></noRegion></country><country name="Royaume-Uni"><noRegion><name sortKey="Savic, Sinisa" sort="Savic, Sinisa" uniqKey="Savic S" first="Sinisa" last="Savic">Sinisa Savic</name></noRegion><name sortKey="Sargur, Ravishankar" sort="Sargur, Ravishankar" uniqKey="Sargur R" first="Ravishankar" last="Sargur">Ravishankar Sargur</name><name sortKey="Sargur, Ravishankar" sort="Sargur, Ravishankar" uniqKey="Sargur R" first="Ravishankar" last="Sargur">Ravishankar Sargur</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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