Autoantibody subclasses

IgG subclasses of autoantibodies (Abs) have been identified using specific monoclonal Abs in the relevant enzyme-linked immunosorbent assays. A skewed pattern of subclasses was thus documented in most auto-Ab systems, depending on the target autoantigen. Furthermore, their profile may differ for each serum sample in a given disease. The serum concentrations of the IgG1 and IgG3 dsDNA Abs correlate with their functional affinity, and with disease activity, most notably renal damages. That is, the rank order of anti-dsDNA IgG subclasses gives an account of the clinical presentation. Remarkably, IgG1 and IgG2 predominate in the presence of nephritis, and the increase in the level of anti-nucleosome IgG3 heralds SLE flares. Although the profile of IgG subclass may differ for each serum sample with mainly one subclass predominating, there is an overall prevailing isotype in each disease. Absence or decrease of Ag-specific IgG subclasses in such sera could simply result from their deposition in tissue sites. Isotype restriction in autoimmune diseases might even be because of an unidentified environmental agent interacting with genetically determined abnormal immune response. In any case, caution must be exercised in interpreting the results of IgG subclass-specific assays, given the methodological pitfalls in such measurements.