Table 1

Cases of T1D in patients with STAT3 GOF mutations currently described in the literature

PatientSTAT3 mutationTID HLA typeAge at diagnosis (weeks)Concomitant manifestationsIslet cell–specific AAbsTh17/Treg alterationReference
Patient 1p.Thr716MetDRB1*03-DQB1*02/DRB1*03-DQB1*02 (high risk)2Celiac disease; primary hypothyroidismPositiveNot describedFlanagan et al. (30) (patient 2 also presented by Haapaniemi et al. [31])
Patient 2p.Lys392ArgDRB1*04-DQB1*0302 (high risk)0Celiac disease; desquamative interstitial pneumonitis; T cell large granular lymphocyte leukemiaPositiveYes
Patient 3p.Asn646LysDQA1*01-B1*05/DQA1*01 (low risk)3EczemaNegativeNot described
Patient 4p.Asn646LysDQA1*03-B1*03:02/A1*01-B1*06:02 (low risk)43Eczema; juvenile arthritisPositiveNot described
Patient 5p.Arg152TrpNot describedNot describedLymphoproliferation; recurrent herpes zoster; lung nodulesNot describedYesMilner et al. (32)
Patient 6p.Glu415LysNot describedNot describedEnteropathy; achalasia; atopic dermatitis; lymphoproliferation; lung nodules; short stature; recurrent urinary tract infectionsNot describedYes
  • The four patients described by Flanagan et al. (30) presented with early-onset T1D with positive antibody detection in patients 1, 2, and 4. Patients 3 and 4 developed diabetes in a context of low-risk HLA predisposition, where patient 3 was also negative in autoantibody screening. In light of these findings, we can hypothesize a fundamental role of cellular-mediated immunity in T1D pathogenesis, at least in the context of STAT3 GOF mutations.