Progranulin antibodies in autoimmune diseases

Lorenz Thurner, Klaus Dieter Preuss, Natalie Fadle, Evi Regitz, Philipp Klemm, Marina Zaks, Maria Kemele, Andrea Hasenfus, Elena Csernok, Wolfgang L. Gross, Jean Louis Pasquali, Thierry Martin, Rainer Maria Bohle, Michael Pfreundschuh*

*Korrespondierende/r Autor/-in für diese Arbeit
31 Zitate (Scopus)

Abstract

Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis.
OriginalspracheEnglisch
ZeitschriftJournal of Autoimmunity
Jahrgang42
Seiten (von - bis)29-38
Seitenumfang10
ISSN0896-8411
DOIs
PublikationsstatusVeröffentlicht - 01.05.2013

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