dorsal/arxiv
View SchemaFunctional immunomics: Microarray analysis of IgG autoantibody repertoires predicts the future response of NOD mice to an inducer of accelerated diabetes
| Authors | Francisco J. Quintana, Peter H. Hagedorn, Gad Elizur, Yifat Marbel, Eytan Domany, Irun R. Cohen |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0409018 |
| URL | https://arxiv.org/abs/q-bio/0409018 |
| DOI | 10.1073/pnas.0404848101 |
Abstract
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 non-obese diabetic (NOD) 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 while 10 mice permanently resisted diabetes. We again obtained serum from each mouse afterCAD induction. We then analyzed the patterns of antibodies in the individualmice to 266 different antigens spotted on the antigen chip. We identified a select panel of 27 different antigens (10% of the array) that revealed a pattern of IgG antibody reactivity in the pre-CAD serathat 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 criticalfor 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.
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"abstract": "One\u0027s present repertoire of antibodies encodes the history of one\u0027s past\nimmunological experience. Can the present autoantibody repertoire be consulted\nto predict resistance or susceptibility to the future development of an\nautoimmune disease? Here we developed an antigen microarray chip and used\nbioinformatic analysis to study a model of type 1 diabetes developing in\nnon-obese diabetic (NOD) male mice in which the disease was accelerated and\nsynchronized by exposing the mice to cyclophosphamide at 4 weeks of age. We\nobtained sera from 19 individual mice, treated the mice to induce\ncyclophosphamide-accelerated diabetes (CAD), and found, as expected, that 9\nmice became severely diabetic while 10 mice permanently resisted diabetes. We\nagain obtained serum from each mouse afterCAD induction. We then analyzed the\npatterns of antibodies in the individualmice to 266 different antigens spotted\non the antigen chip. We identified a select panel of 27 different antigens (10%\nof the array) that revealed a pattern of IgG antibody reactivity in the pre-CAD\nserathat discriminated between the mice resistant or susceptible to CAD with\n100% sensitivity and 82% specificity (p=0.017). Surprisingly, the set of IgG\nantibodies that was informative before CAD induction did not separate the\nresistant and susceptible groups after the onset of CAD; new antigens became\ncriticalfor post-CAD repertoire discrimination. Thus, at least for a model\ndisease, present antibody repertoires can predict future disease; predictive\nand diagnostic repertoires can differ; and decisive information about immune\nsystem behavior can be mined by bioinformatic technology. Repertoires matter.",
"arxiv_id": "q-bio/0409018",
"authors": [
"Francisco J. Quintana",
"Peter H. Hagedorn",
"Gad Elizur",
"Yifat Marbel",
"Eytan Domany",
"Irun R. Cohen"
],
"categories": [
"q-bio.TO",
"q-bio.QM"
],
"doi": "10.1073/pnas.0404848101",
"title": "Functional immunomics: Microarray analysis of IgG autoantibody repertoires predicts the future response of NOD mice to an inducer of accelerated diabetes",
"url": "https://arxiv.org/abs/q-bio/0409018"
},
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