Table 1

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

Patient	STAT3 mutation	TID HLA type	Age at diagnosis (weeks)	Concomitant manifestations	Islet cell–specific AAbs	Th17/Treg alteration	Reference
Patient 1	p.Thr716Met	DRB103-DQB102/DRB103-DQB102 (high risk)	2	Celiac disease; primary hypothyroidism	Positive	Not described	Flanagan et al. (30) (patient 2 also presented by Haapaniemi et al. [31])
Patient 2	p.Lys392Arg	DRB104-DQB10302 (high risk)	0	Celiac disease; desquamative interstitial pneumonitis; T cell large granular lymphocyte leukemia	Positive	Yes
Patient 3	p.Asn646Lys	DQA101-B105/DQA1*01 (low risk)	3	Eczema	Negative	Not described
Patient 4	p.Asn646Lys	DQA103-B103:02/A101-B106:02 (low risk)	43	Eczema; juvenile arthritis	Positive	Not described
Patient 5	p.Arg152Trp	Not described	Not described	Lymphoproliferation; recurrent herpes zoster; lung nodules	Not described	Yes	Milner et al. (32)
Patient 6	p.Glu415Lys	Not described	Not described	Enteropathy; achalasia; atopic dermatitis; lymphoproliferation; lung nodules; short stature; recurrent urinary tract infections	Not described	Yes	Milner et al. (32)

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.