ANCA subclasses in IgG4-related disease and ANCA-associated vasculitis

Abstract

Introduction IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition characterized by fibrotic lesions with lymphoplasmacytic infiltration in one or more organs. Differential diagnosis from ANCA-associated vasculitis (AAV) can be difficult and AAV-IgG4-RD overlap has been reported. Anti-neutrophil cytoplasm antibodies (ANCA) are a hallmark of AAV and ANCA of IgG4 subclass have been detected in AAV-IgG4-RD overlap, but the role of IgG4 ANCA in differentiating AAV and IgG4-RD is presently unclear. Material and methods Anti-myeloperoxidase antibodies of each IgG subclass were detected by ELISA in 20 IgG4-RD ANCA-negative patients, in 35 ANCA-MPO+ AAV and in one AAV-IgG4-RD overlap patient. Results In the IgG4-RD cohort, 7 patients are positive for at least one ANCA-MPO subclass, but antibody amounts are very low compared to AAV. In the AAV-IgG4-RD overlap patient, only IgG2-ANCA and IgG3-ANCA are detected. AAV patients in the active phase of the disease present higher amounts of IgG4 ANCA-MPO; on the contrary, ANCA-MPO subclass-positive IgG4-RD patients do not display a higher disease activity. In AAV patients, co-expression of more than one ANCA-MPO subclass is associated with higher disease activity, while no such relation can be established in IgG4-RD. Conclusions Evaluation of ANCA subclasses does not help in phenotyping IgG4-RD patients. The lack of correlation with disease activity in IgG4-RD and the distribution of ANCA subclasses in the overlap patient suggest that ANCA-MPO do not play a major role in IgG4-RD.