Similar immunophenotype shifts to immunosenescence were observed in patients with genetic defects resulting in their failure to control lymphocyte activation (activated PI3K, activated STAT3 or LRBA deficiency, unpublished observation), and immunosenescence is thought to contribute to autoimmunity in rheumatoid arthritis development44. Here, STAT3 is linked to hyperinsulinemic hypoglycemia, familial, 4.