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T cell Polarization toward T(H)2/T(FH)2 and T(H)17/T(FH)17 in Patients with IgG4-related Disease
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International audience. IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease's pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocyte's subsets were analyzed by flow cytometry, with analysis of T(H)1/T(H)2/T(H)17, T-FH cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy controls and to patients with primary Sjogren's syndrome. Patients with IgG4-RD showed an increase of circulating T regulatory, T(H)2, T(H)17, and CD4(+)CXCR5(+)PD1(+) TFH cell subsets. Accordingly, increased levels of IL-10 and IL-4 were measured in IgG-RD patients. TFH increase was characterized by the specific expansion of T(FH)2 (CCR6(-)CXCR3(-)), and to a lesser extent of (T(FH)17 (CCR6(+)CXCR3(-))) cells. Interestingly, CD4(+)CXCR5(+)PD1(+) TFH cells normalized under treatment. IgG4-RD is characterized by a shift of circulating T cells toward a T(H)2/T(FH)2 and T(H)17/T(FH)17 polarization. This immunological imbalance might be implicated in the disease's pathophysiology. Treatment regimens targeting such T cells warrant further evaluation.
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