A step closer to understanding the predisposition to autoimmunity as well humoral defects in aging patients with 22q11.2 deletion syndrome

Abstract

IntroductionOur previous work has shown that despite having a small thymus with a limited T cell repertoire, the majority of patients with 22q11.2 deletion syndrome have a normal T cell proliferation at young age. As these patients age, their T cell numbers normalize yet about 25% have recurrent sinopulmonary infections and autoimmune disease, suggesting that their Tcell compartment exhibits some dysregulation. Follicular helper T cells (Tfh) are crucial for humoral immunity (germinal center formation, affinity maturation, memory B cell formation), yet there has been emerging evidence showing that Tfh cells contribute to the pathogenesis of autoimmune disease such as SLE where Tfh correlate with titers of autoantibodies and the severity of end-organ involvement. Similarly, Tfh cells play a role in the of autoimmunity in diseases of immune dysregulation such as CTLA-4 deficiency and IPEX syndrome where abundant Tfh cells may facilitate breakdown of the peripheral tolerance of autoreactive B cells. Given the crucial role Tfh cells play humoral immunity and occasionally autoimmunity we sought to look at the percentage of Tfh cells in older patients with 22q11.2 deletion syndrome. MethodsWe compared the percentage of peripheral blood Tfh cells in 16 patients with 22q11.2 (age range 9–38 years) to age-matched healthy controls. T-tests were used to define significance. ResultsTfh cells in patients with 22q11.2 deletion syndrome were statistically significantly higher when compared to healthy controls, 19% and 8% respectively, Figure 1. DiscussionWe hypothesize that the observed increase in Tfh cells population in older 22q11.2 deletion patients is contributing to their autoimmune propensity. Our finding aligns with others who reported Tfh cells to play a role in the pathogenesis of autoimmunity seen in immune dysregulation syndromes. Further understanding the intrinsic characteristics of Tfh cells in these patients could be helpful in identifying the subset of patients at risk of antibody deficiency as well autoimmunity. [Display omitted]