T Cell Polarization toward T2/T2 and T17/T17 in Patients with IgG4-Related Disease.

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. Lymphocytes' subsets were analyzed by flow cytometry, with analysis of T1/T2/T17, T cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy controls and to patients with primary Sjögren's syndrome. Patients with IgG4-RD showed an increase of circulating T regulatory, T2, T17, and CD4CXCR5PD1 T cell subsets. Accordingly, increased levels of IL-10 and IL-4 were measured in IgG-RD patients. T increase was characterized by the specific expansion of T2 (CCR6CXCR3), and to a lesser extent of T17 (CCR6CXCR3) cells. Interestingly, CD4CXCR5PD1 T cells normalized under treatment. IgG4-RD is characterized by a shift of circulating T cells toward a T2/T2 and T17/T17 polarization. This immunological imbalance might be implicated in the disease's pathophysiology. Treatment regimens targeting such T cells warrant further evaluation.