T CELL PROLIFERATION AGAINST MYELIN, PANCREATIC, AND DIETARY ANTIGENS IN CHILDREN: AUTOIMMUNITY IS DETECTABLE EARLY IN CNS DEMYELINATION AND TYPE I DIABETES

Objectives: Adults with autoimmune disease have shown enhanced T cell proliferation against target organ and nutritional antigens. It is unknown whether this occurs early, or as a sequelae of chronic autoimmunity. Our objective is to evaluate T cell proliferative responses in children with CNS demyelination compared to healthy and disease controls.

Methods: Peripheral mononuclear cells were freshly isolated from venous blood and analyzed for T cell stimulation indices to target, dietary, and control antigens.

Results: We studied 166 children: 63 with CNS demyelination (26 Multiple Sclerosis, 37 CIS), 43 with type I diabetes, 31 with non-autoimmune neurological conditions, and 30 healthy children. T cell proliferation against myelin antigens was uncommon in healthy children (10%) compared to children with MS (50%, p=0.0023) or CIS (51%, p=0.0005). Pancreatic antigens were targeted by over 90% of children with diabetes, compared to only 14% of healthy controls (p<0.0001). T cell responses were not disease-specific as 79% of diabetics showed reactivity against myelin, and 30% of MS and 20% of CIS children reacted to proinsulin. Children with diabetes, but not MS or CIS, target pancreatic antigens, Tep69, GAD, GAD555. MS, CIS, and diabetic children show a prominent T cell response against milk antigens. Reactivity to BSA193 (a milk antigen capable of inducing murine autoimmune demyelination) was targeted by over 60% of the MS and CIS cohorts, rarely by healthy children, and not by children with diabetes. Reactivity to BSA150 (associated with murine insulitis) was detected in over 90% of diabetics, but was absent in MS, CIS, and healthy cohorts.

Conclusion: Even at onset, children with autoimmune disease harbor T cells that proliferate against tissue-related antigens, and epitope-specific responses distinguish children with demyelination from diabetes. T cell responses against milk antigens raise the possibility that nutrition-directed immune reactivity may be associated with autoimmunity.