Artikel
Differential presence of autoantibodies recognizing G protein-coupled receptors and relation to clinical parameters in ANCA-associated Vasculitis
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Veröffentlicht: | 4. September 2017 |
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Gliederung
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Background: Apart from ANCA targeting either myeloperoxidase (MPO) or proteinase 3 (PR3), antibodies recognizing other autoantigens may have a role as diagnostic markers or represent a link to pathogenetic events in ANCA-associated vasculitis (AAV). However, evidence for a role of autoantibodies in AAV other than in MPO- and PR3-ANCA is scarce and in some instances highly controversial, e.g. in the case of LAMP-2 ANCA. More recently, antibodies binding to pentraxin 3 have been suggested as biomarker in AAV and antibodies directed against progranulin have been associated with a pro-inflammatory function in GPA.
Methods: This study examined the presence of autoantibodies targeting G protein-coupled receptors [GPCR; angiotensin II type 1 receptor antibodies (anti-AT1R), endothelin-1 type A receptor antibodies (anti-ETAR), protease-activated receptor 1 and 2 antibodies (anti-PAR-1, anti-PAR-2) muscarinic acetylcholine receptor antibodies (anti-M1, anti-M2, anti-M3, anti-M4)] in sera of patients with AAV [granulomatosis with polyangiitis (GPA), n=49; microscopic polyangiitis (MPA), n=18] and healthy controls [HC, (n=217)] by measuring their titers using ELISA. Clinical data (BVAS, VDI, therapy), inflammatory markers (ESR, C-reactive protein, creatinine, proteinuria) and diagnostic autoantibodies (PR3- and MPO-ANCA) were gathered at the time of serum sampling.
Results: There was an increased titer of anti-AT1R antibodies in GPA when compared to HC. GPA patients who were not treated with cyclophosphamide showed a positive correlation between anti-AT1R antibodies and BVAS. Reduced levels of anti-ETAR antibodies were observed in MPA and anti-ETAR antibodies negatively correlated with BVAS. Decreased concentrations of anti-PAR-1 and anti-PAR-2 antibodies were detected in both GPA and MPA. Further, there was a positive correlation between anti-PAR-1 antibodies and PR3-ANCA and a negative correlation between anti-PAR-2 antibodies and BVAS in GPA. Interestingly, decreased levels of anti-M4 antibodies were found in both GPA and MPA.
Conclusion: Circulating autoantibodies targeting GPCR could be of diagnostic value in identifying clinical progress and/or subgroups in AAV. Their role in the pathophysiology, e.g. their impact on endothelial damage and the induction of vasculitis, has to be further investigated in AAV