Perigranuloma Localization and Abnormal Maturation of B Cells

• DOI: 10.1164/rccm.201206-1024oc
• Publication Date: 2012-12-14T07:36:02Z
• Authors: Lieke S. Kamphuis; Menno C. van Zelm; King H. Lam; Guus F. Rimmelzwaan; G. Seerp Baarsma; Willem A. Dik; H. Bing Thio; Paul L. van Daele; Mirjam E. van Vel...; Manou R. Batstra; P. Martin van Hagen; Jan A. van Laar
• Keywords: Memory B cell; Pathogenesis; Immunoglobulin A; B-1 cell; Immunoglobulin D

Recent observations of abnormal immunoglobulin responses and case reports describing successful B-cell ablative therapy suggest involvement B cells in the pathogenesis sarcoidosis.To investigate how maturation function patients with sarcoidosis contribute to disease.Patients (n = 32) were included for detailed analysis by immunohistochemistry tissue, flow cytometry blood subsets, serum levels. Vaccination influenza virus encapsulated bacteria molecular heavy chain transcripts studied functional responses.Perigranuloma localization IgA-producing plasma numerous found affected tissues. Total numbers normal, CD27(+) memory significantly reduced, CD27(-)IgA(+) increased; results are normalized treated TNF-α blockers. Despite this, had normal levels antigen-specific responses. IgA IgG transcripts, however, showed high frequencies somatic hypermutations increased usage downstream subclasses, suggestive prolonged or repetitive responses.The large infiltrates granulomatous tissue signs antibody indicative direct local inflammatory processes sarcoidosis. Moreover, could be a marker treatment These findings as emerging key players provide rationale systematic study on