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Sarcoidosis and molecular mimicry—important etiopathogenetic aspects: current state and future directions

Identifieur interne : 000542 ( Istex/Curation ); précédent : 000541; suivant : 000543

Sarcoidosis and molecular mimicry—important etiopathogenetic aspects: current state and future directions

Auteurs : Georgi Tchernev [Bulgarie, Allemagne] ; Julian Ananiev [Bulgarie] ; José Carlos Cardoso [Portugal] ; Uwe Wollina [Allemagne] ; Shyam B. Verma [Inde] ; James W. Patterson [États-Unis] ; Lyubomir A. Dourmishev [Bulgarie] ; Michael Tronnier [Allemagne] ; Hiroyuki Okamoto [Japon] ; Kana Mizuno [Japon] ; Nobuo Kanazawa [Japon] ; Maya Gulubova [Bulgarie] ; Irena Manolova [Bulgarie] ; Cristina Salaro

Source :

RBID : ISTEX:F2AAB36CA74C2CEE4BFE6270B7357F665F0A81DA

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English descriptors

Abstract

Summary: Sarcoidosis is a disease of uncertainty in terms of its cause, presentation, and clinical course. The disease has a worldwide distribution and affects all ages, races, and both sex. Sarcoidosis of the skin may have an extremely heterogeneous clinical presentation, so that the definitions of ‘great imitator’ and ‘clinical chameleon’ have long been used. The factors that influence clinical picture and severity of the disease are probably linked to the etiopathogenesis of sarcoidosis, which continues to be shrouded in mystery. The current state of the art on the pathogenesis of sarcoidosis is that it is an immunological response in a genetically susceptible individual to an as-yet undefined antigenic stimulus. How exposure occurs in genetically predisposed patients is not completely clear, but the most likely explanation is that these agents or antigens are either inhaled into the lungs or enter through contact with the skin, as these are the common target organs that are constantly in contact with the environment. An autoimmune etiology of sarcoidosis could possibly occur through a process of molecular mimicry of infectious or other environmental antigens to host antigens. This could lead to a cross-mediated immune response and induction of autoimmune disease. This molecular mimicry may probably be responsible for the heterogeneous clinical presentations of the disease. Several investigations and studies have provided valuable evidence on the etiopathogenesis of sarcoidosis, which may lead to the future development of targeted and innovative treatment strategies. Nevertheless, we are still a long way from unravelling the underlying cause of this mysterious disease.
Zusammenfassung: Die Sarkoidose ist eine Erkrankung voll der Unsicherheiten in Bezug auf ihre Ursache, Präsentation und den klinischen Verlauf. Die Erkrankung kommt überall auf der Welt vor. Sie tritt in jedem Alter, bei allen Rassen bei Mann und Frau auf. Die Sarkoidose der Haut kann sich klinisch extrem unterschiedlich präsentieren – seit Langem wird sie daher auch als „Großer Nachahmer“ und „klinisches Chamäleon“ bezeichnet. Die Faktoren, die das klinische Bild und die Schwere der Erkrankung beeinflussen, sind wahrscheinlich mit der Ätiopathogenese der Erkrankung verbunden. Diese sind aber auch heute noch immer ungeklärt. Die aktuelle Lehrmeinung besagt, dass die Sarkoidose eine immunologische Antwort auf einen bis jetzt undefinierten antigenen Reiz in einem – genetisch bedingt – empfindlichen Individuum darstellt. Wie es zur Exposition der genetisch prädisponierten Patienten kommt ist nicht ganz klar. Die wahrscheinlichste Erklärung ist, dass diese Substanzen, beziehungsweise Antigene entweder über die Lungen inhaliert werden oder durch Kontakt mit der Haut in den Körper eintreten. Haut und Lunge sind die am häufigsten befallenen Zielorgane, die dauernd mit der Umwelt in Kontakt stehen. Eine autoimmune Ätiologie der Sarkoidose könnte möglicherweise durch einen Prozess der molekularen Mimikrie von infektiösen oder anderen Antigenen aus der Umwelt auf Wirt Antigene erklärt werden. Dadurch könnte es zu einer „cross mediated“ Immunantwort und Auslösung einer autoimmunen Erkrankung kommen. Diese molekulare Mimikrie kann möglicherweise für die unterschiedliche klinische Präsentation der Erkrankung verantwortlich sein. Verschiedene Untersuchungen und Studien haben wertvolle Evidenz in Bezug auf die Ätiopathogenese der Sarkoidose geliefert. Dadurch könnte es in der Zukunft zur Entwicklung von zielgerichteten neuen Behandlungsstrategien kommen. Heute sind wir allerdings trotz allem noch weit entfernt von der Entwirrung der zugrunde liegenden Ursache dieser geheimnisvollen Krankheit.

Url:
DOI: 10.1007/s00508-012-0154-9

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ISTEX:F2AAB36CA74C2CEE4BFE6270B7357F665F0A81DA

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Cristina Salaro
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<div type="abstract" xml:lang="en">Summary: Sarcoidosis is a disease of uncertainty in terms of its cause, presentation, and clinical course. The disease has a worldwide distribution and affects all ages, races, and both sex. Sarcoidosis of the skin may have an extremely heterogeneous clinical presentation, so that the definitions of ‘great imitator’ and ‘clinical chameleon’ have long been used. The factors that influence clinical picture and severity of the disease are probably linked to the etiopathogenesis of sarcoidosis, which continues to be shrouded in mystery. The current state of the art on the pathogenesis of sarcoidosis is that it is an immunological response in a genetically susceptible individual to an as-yet undefined antigenic stimulus. How exposure occurs in genetically predisposed patients is not completely clear, but the most likely explanation is that these agents or antigens are either inhaled into the lungs or enter through contact with the skin, as these are the common target organs that are constantly in contact with the environment. An autoimmune etiology of sarcoidosis could possibly occur through a process of molecular mimicry of infectious or other environmental antigens to host antigens. This could lead to a cross-mediated immune response and induction of autoimmune disease. This molecular mimicry may probably be responsible for the heterogeneous clinical presentations of the disease. Several investigations and studies have provided valuable evidence on the etiopathogenesis of sarcoidosis, which may lead to the future development of targeted and innovative treatment strategies. Nevertheless, we are still a long way from unravelling the underlying cause of this mysterious disease.</div>
<div type="abstract" xml:lang="de">Zusammenfassung: Die Sarkoidose ist eine Erkrankung voll der Unsicherheiten in Bezug auf ihre Ursache, Präsentation und den klinischen Verlauf. Die Erkrankung kommt überall auf der Welt vor. Sie tritt in jedem Alter, bei allen Rassen bei Mann und Frau auf. Die Sarkoidose der Haut kann sich klinisch extrem unterschiedlich präsentieren – seit Langem wird sie daher auch als „Großer Nachahmer“ und „klinisches Chamäleon“ bezeichnet. Die Faktoren, die das klinische Bild und die Schwere der Erkrankung beeinflussen, sind wahrscheinlich mit der Ätiopathogenese der Erkrankung verbunden. Diese sind aber auch heute noch immer ungeklärt. Die aktuelle Lehrmeinung besagt, dass die Sarkoidose eine immunologische Antwort auf einen bis jetzt undefinierten antigenen Reiz in einem – genetisch bedingt – empfindlichen Individuum darstellt. Wie es zur Exposition der genetisch prädisponierten Patienten kommt ist nicht ganz klar. Die wahrscheinlichste Erklärung ist, dass diese Substanzen, beziehungsweise Antigene entweder über die Lungen inhaliert werden oder durch Kontakt mit der Haut in den Körper eintreten. Haut und Lunge sind die am häufigsten befallenen Zielorgane, die dauernd mit der Umwelt in Kontakt stehen. Eine autoimmune Ätiologie der Sarkoidose könnte möglicherweise durch einen Prozess der molekularen Mimikrie von infektiösen oder anderen Antigenen aus der Umwelt auf Wirt Antigene erklärt werden. Dadurch könnte es zu einer „cross mediated“ Immunantwort und Auslösung einer autoimmunen Erkrankung kommen. Diese molekulare Mimikrie kann möglicherweise für die unterschiedliche klinische Präsentation der Erkrankung verantwortlich sein. Verschiedene Untersuchungen und Studien haben wertvolle Evidenz in Bezug auf die Ätiopathogenese der Sarkoidose geliefert. Dadurch könnte es in der Zukunft zur Entwicklung von zielgerichteten neuen Behandlungsstrategien kommen. Heute sind wir allerdings trotz allem noch weit entfernt von der Entwirrung der zugrunde liegenden Ursache dieser geheimnisvollen Krankheit.</div>
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