Increase of follicular helper T cells skewed toward a Th1 profile in CVID patients with non-infectious clinical complications

Common variable immunodeficiency (CVID) is characterized by low levels of circulating immunoglobulins and defects in B cell maturation leading to an increased susceptibility to infections. Some patients develop complications such as autoimmune diseases, enteropathy, and lymphoproliferation, resulting in higher morbidity and mortality. Follicular helper T (TFH) cells are specialized in helping B cell differentiation into Ig-producing cells. Three subsets have been described, namely non B-cell helper TFH1 and the two B-helper cell subsets TFH2 and TFH17. We determined that circulating Tell cells were elevated in CVID patients and skewed toward a Tail profile. Interestingly, elevated levels of TFH1 cells were significant only in patients harboring non-infectious complications regardless of the type of complication and inversely correlated with switched memory B cells. Moreover, CXCR3(+) cells are increased in splenic CVID germinal centers. Our observations suggest that the altered balance in TFH subsets in CVID is linked to a more severe disease.