Background/Purpose:

IgG4 related disease (IgG4-RD) is a systemic disease that is characterized by the infiltration of IgG4secreting plasma cells and effector T cells into various organs. However, the characteristics and pathological role of immune cell subsets remain unclear. The aim of this study was to investigate the characteristic phenotype of immune cell subsets in IgG4-RD.

Methods:

Peripheral blood mononuclear cells were obtained from 16 patients with IgG4-RD, 4 with primary Sjogren syndrome (pSS) and 23 healthy donors (HD). The phenotype of circulating B cells, T cells were defined based on comprehensive flow cytometric analysis for human immune system termed ‘the Human Immunology Project’ by NIH/FOCIS. CD4⁺Bcl-6⁺ T follicular helper (Tfh) cells were detected by immunohistochemistry in salivary glands obtained by the biopsy.

Results:

Baseline characteristics of patients with IgG4-RD were (means); age 60 years old, symptom duration 19 months, serum IgG 2735 mg/dl, IgG4 694 mg/dl, CRP 0.7 mg/dl. The proportions of CD3⁺CD4⁺CD45RA^–CCR7^– effector memory T cells, CD3⁺CD4⁺CD45RA⁺CCR7^– effector T helper cells increased, whereas naive T cells decreased in IgG4-RD, compared to HD and pSS. There was no difference in the proportion of well known helper T cell subsets (Th1, Th17, and Treg) between IgG4-RD, pSS and HD. On the other hand, the proportions of CD4⁺CXCR5⁺ICOS⁺ Tfh and CD19⁺CD20^–CD27⁺CD38⁺ plasmablasts were significant higher in IgG4-RD, compared to pSS and HD. Moreover, the proportion of Tfh in peripheral blood tended to be higher in patients whose Tfh more densely accumulated in the salivary gland. Among multiple immune cell subsets, the proportion of Tfh and that of plasmablasts were positively correlated, revealing statistical clustering. Of note, the percentage of plasmablasts was correlated with serum IgG levels. Furthermore, the proportion of plasmablasts and that of Tfh were higher in patients with extra glandular manifestations, compared to patients without them. After treatment with glucocorticoids, the proportion of plasmablasts and that of Tfh decreased with the improvement of clinical manifestations.

Conclusion: These results revealed that the higher proportion of Tfh cells and plasmablasts is characteristically observed in IgG4-RD. The frequency of Tfh was correlated with that of plasmablasts, and the Tfh/plasmablast axis contributed to organ manifestation of IgG4-RD. Our findings would clarify the pathogenesis of IgG4-RD through the interaction between Tfh cells and plasmablasts and suggest a potential as the therapeutic target of this disease.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/characterization-of-peripheral-lymphocyte-phenotype-in-patients-with-igg4-related-disease/