T follicular helper cell expansion and chronic T cell activation are characteristic immune anomalies in Evans syndrome.

Pediatric Evans syndrome (pES) is increasingly identified as the presenting manifestation of several inborn errors of immunity (IEI). Despite an improved understanding of genetic defects in pES, the underlying immunobiology of pES is poorly defined, and characteristic diagnostic immune parameters are lacking. We describe the immune characteristics of 24 patients with pES and compared them with 22 patients with chronic immune thrombocytopenia (cITP) and 24 healthy controls (HC). Compared to patients with cITP and HC, patients with pES had increased circulating T-follicular helper cells (cTfh), increased T cell activation, and decreased naive CD4+ T cells for age. Despite normal or high IgG in the majority of pES at presentation, class-switched memory B cells (CSMB) were decreased. Within the cTfh subset, we noted features of post-activation exhaustion with upregulation of several canonical checkpoint inhibitors. TCR-b repertoire analysis of cTfh cells revealed increased oligoclonality in patients with pES compared with HC. Among patients with pES, those without a known gene defect had a similar characteristic immune abnormality as patients with defined genetic defects. Similarly, patients with pES with normal IgG had similar T cell abnormalities as patients with low IgG. Since genetic defects have been identified in only less than half of patients with pES, our findings of similar immune abnormalities across all pES patients help establish a common characteristic immunopathology in pES irrespective of the underlying genetic etiology.