Abnormal T-cell re-activities in childhood inflammatory demyelinating disease and type 1 diabetes.

OBJECTIVES:

Pediatric-onset multiple sclerosis offers a unique window into early targets and mechanisms of immune dysregulation.  It is unknown whether heightened T-cell reactivities documented in adult patients, to both target-organ and environmental antigens, emerge in parallel or develop as early or late events.  

Our objectives were to determine the presence, pattern, and specificity of abnormal T-cell reactivities to such antigens in the earliest stages of the multiple sclerosis process.

METHODS:

Peripheral T-cell proliferative responses to self-, dietary and control antigens were blindly evaluated in a large cohort of well-characterized children (n = 172) with central nervous system (CNS) inflammatory demyelination (n = 63), recent-onset type 1 (insulin-dependent) diabetes mellitus (T1D; n = 41), non-autoimmune neurological conditions (n = 39), and healthy children (n = 29).

RESULTS:

Children with inflammatory demyelination, CNS injury, and T1D exhibited heightened T-cell reactivities to self-antigens, and these responses were not strictly limited to the disease target organs. Children with autoimmune disease and CNS injury also exhibited abnormal T-cell responses against multiple cow-milk proteins. Responses to specific milk epitopes (An influencing or determining element or factor) distinguished T1D from inflammatory demyelination and other neurological diseases.

INTERPRETATION:

Abnormal T-cell reactivities to self- and environmental antigens manifest in the earliest clinical stages of inflammatory demyelination and T1D. The pattern of heightened T-cell reactivities implicates both shared and distinct mechanisms of immune dysregulation in the different autoimmune diseases.  Abnormal T-cell responses in children with tissue injury challenge the prevailing view that CNS autoreactive cells inherently mediate the disease in early multiple sclerosis.    

Division of Neurology,

Department of Pediatrics and the Research Institute,

The Hospital for Sick Children,

University of Toronto,

Toronto, Canada.