Biomarker discovery in pre-Type 1 Diabetes; Th40 cells as a predictive risk factor.

Abstract

CONTEXT\nThe incidence of Type 1 Diabetes (T1D) is increasing worldwide. The quest to understand T1D etiology as well as how to predict diabetes is ongoing and, in many ways, those goals intertwine. While genetic components associate with T1D, not all T1D individuals have those components and not all subjects with those components develop disease.\n\n\nOBJECTIVE\nMore robust methods for prediction of T1D are needed. Can high CD4+CD40+ T cell (Th40) levels be used as a biomarker in addition to other markers?\n\n\nMETHODS\nTh40 levels were assessed along with other parameters in blood collected from prediabetic TrialNet subjects.\n\n\nRESULTS\nPre-diabetic subjects, stratified according to their Th40 cell levels, demonstrate patterns that parallel those seen between control and T1D subjects. Cytokine patterns are significantly different between Th40-high and -low subjects and a CD4/CD8 double-positive population is more represented in Th40-high groups. Subjects experiencing impaired glucose tolerance present a significantly higher Th40 level than control subjects do. HLA DR4/DR4 and DQ8/DQ8, HLAs associated with T1D, are more likely found among Th40-high subjects. Interestingly, HLA DR4/DR4 subjects were significantly older compared with all other subjects, suggesting that this haplotype together with a high Th40 level may represent someone who will onset after age 30, which is reported for 42% of T1D cases.\n\n\nCONCLUSION\nConsidering the differences found in relation to prediabetic Th40 cell level, it may be possible to devise methods that more accurately predicts who will proceed toward diabetes and, possibly, at what stage of prediabetes a subject is.