Circulating TFH Subset Distribution Is Strongly Affected in Lupus Patients with an Active Disease

Follicular helper T cells (T-FH) represent a distinct subset of CD4(+) T cells specialized in providing help to B lymphocytes, which may play a central role in autoimmune diseases having a major B cell component such as systemic lupus erythematosus. Recently, T-FH subsets that share common phenotypic and functional characteristics with T-FH cells from germinal centers, have been described in the peripheral blood from healthy individuals. The aim of this study was to analyze the distribution of such populations in lupus patients. Circulating T-FH cell subsets were defined by multicolor flow cytometry as T(FH)17 (CXCR3(-)CCR6(+)), T(FH)1 (CXCR3(+) CCR6(-)) or T(FH)2 (CXCR3(-)CCR6(-)) cells among CXCR5(+) CD45RA(-)CD4(+) T cells in the peripheral blood of 23 SLE patients and 23 sex and age-matched healthy controls. IL-21 receptor expression by B cells was analyzed by flow cytometry and the serum levels of IL-21 and Igs were determined by ELISA tests. We found that the T(FH)2 cell subset frequency is strongly and significantly increased in lupus patients with an active disease (SLEDAI score>8), while the T(FH)1 cell subset percentage is greatly decreased. The T(FH)2 and T(FH)1 cell subset frequency alteration is associated with the presence of high Ig levels and autoantibodies in patient's sera. Moreover, the T(FH)2 cell subset enhancement correlates with an increased frequency of double negative memory B cells (CD27(-)IgD(-)CD19(+) cells) expressing the IL-21R. Finally, we found that IgE levels in lupus patients' sera correlate with disease activity and seem to be associated with high T(FH)2 cell subset frequency. In conclusion, our study describes for the first time the distribution of circulating T-FH cell subsets in lupus patients. Interestingly, we found an increased frequency of T(FH)2 cells, which correlates with disease activity. Our results suggest that this subset might play a key role in lupus pathogenesis.