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Our antigen microarrays can identify antigen-specific autoantibody isotypes. Th1-type responses are associated with autoimmune tissue destruction, while Th2-type responses are generally protective. Th1-type immune responses produce IFN and IL-12, and generate antibodies of complement-fixing isotypes (IgG1 and IgG3 in humans; IgG2a in mice) that cause tissue injury. In contrast, Th2 responses produce IL-4 and IL-10, and generate antibodies of non-complement-fixing isotypes (IgG2 and IgG4 in humans; IgG1 in mice). Ability to characterize isotype usage may facilitate identification of offending autoantigens, based on determination of autoantigens against which autoantibodies of pathogenic isotypes are directed. Microarray isotype analysis may provide insight into both B and T cell-autoimmunity, as not only T cells but also effector B cells have been implicated in the reciprocal regulation of polarized Th1 vs. Th2 cytokine production. Therapeutic deviation of immune responses from Th1 to Th2 cytokine production has been associated with efficacious treatment of Th1-mediated immune disease. Current ELISA-based methods require individual wells for analysis of each isotype for each antigen. Antigen arrays have the potential to simultaneously profile multiple antibody isotypes against thousands of candidate autoantigens on a single array.
