title: Progranulin antibodies in autoimmune diseases.
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.
authors.affiliation: Saarland University Medical School, José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, 66421 Homburg/Saar, Germany. Lorenz.Thurner@uks.eu
authors.forename: Lorenz
authors.initials: L
authors.lastname: Thurner
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Preuss
authors.forename: Natalie
authors.initials: N
authors.lastname: Fadle
authors.forename: Evi
authors.initials: E
authors.lastname: Regitz
authors.forename: Philipp
authors.initials: P
authors.lastname: Klemm
authors.forename: Marina
authors.initials: M
authors.lastname: Zaks
authors.forename: Maria
authors.initials: M
authors.lastname: Kemele
authors.forename: Andrea
authors.initials: A
authors.lastname: Hasenfus
authors.forename: Elena
authors.initials: E
authors.lastname: Csernok
authors.forename: Wolfgang L
authors.initials: WL
authors.lastname: Gross
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pasquali
authors.forename: Thierry
authors.initials: T
authors.lastname: Martin
authors.forename: Rainer Maria
authors.initials: RM
authors.lastname: Bohle
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
mesh_terms: D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000276:immunology*; D000077153:Progranulins; D040081:Protein Array Analysis; D056647:Systemic Vasculitis / Q000175:diagnosis / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins