Functional immunomics: microarray analysis of IgG autoantibody repertoires predicts the future response of mice to induced diabetes

FJ Quintana, PH Hagedorn, G Elizur… - Proceedings of the …, 2004 - National Acad Sciences
FJ Quintana, PH Hagedorn, G Elizur, Y Merbl, E Domany, IR Cohen
Proceedings of the National Academy of Sciences, 2004National Acad Sciences
One's present repertoire of antibodies encodes the history of one's past immunological
experience. Can the present autoantibody repertoire be consulted to predict resistance or
susceptibility to the future development of an autoimmune disease? Here, we developed an
antigen microarray chip and used bioinformatic analysis to study a model of type 1 diabetes
developing in nonobese diabetic male mice in which the disease was accelerated and
synchronized by exposing the mice to cyclophosphamide at 4 weeks of age. We obtained …
One's present repertoire of antibodies encodes the history of one's past immunological experience. Can the present autoantibody repertoire be consulted to predict resistance or susceptibility to the future development of an autoimmune disease? Here, we developed an antigen microarray chip and used bioinformatic analysis to study a model of type 1 diabetes developing in nonobese diabetic male mice in which the disease was accelerated and synchronized by exposing the mice to cyclophosphamide at 4 weeks of age. We obtained sera from 19 individual mice, treated the mice to induce cyclophosphamide-accelerated diabetes (CAD), and found, as expected, that 9 mice became severely diabetic, whereas 10 mice permanently resisted diabetes. We again obtained serum from each mouse after CAD induction. We then analyzed, by using rank-order and superparamagnetic clustering, the patterns of antibodies in individual mice to 266 different antigens spotted on the chip. A selected panel of 27 different antigens (10% of the array) revealed a pattern of IgG antibody reactivity in the pre-CAD sera that discriminated between the mice resistant or susceptible to CAD with 100% sensitivity and 82% specificity (P = 0.017). Surprisingly, the set of IgG antibodies that was informative before CAD induction did not separate the resistant and susceptible groups after the onset of CAD; new antigens became critical for post-CAD repertoire discrimination. Thus, at least for a model disease, present antibody repertoires can predict future disease, predictive and diagnostic repertoires can differ, and decisive information about immune system behavior can be mined by bioinformatic technology. Repertoires matter.
National Acad Sciences