AUTOANTIBODIES TO HISTONE, DNA AND NUCLEOSOME ANTIGENS IN CANINE SYSTEMIC LUPUS-ERYTHEMATOSUS

Dogs can develop systemic lupus erythematosus syndromes that are clini cally similar to those seen in humans. In contrast, previous observati ons suggest differences in their autoantibody reactivity patterns agai nst histones and DNA which are components of the nucleosome in chromat in. The objective of this study was to assess comprehensively the leve ls of autoantibodies against histone, DNA and nucleosome antigens in a population of lupus dogs. The specificities of antibodies in lupus an d control dog sera were determined using IgM- and IgG-specific reagent s in an ELISA against a variety of chromatin antigens. When compared w ith control sera, IgG antibodies to individual histones H1, H2A, H3 an d H4 were significantly higher in the lupus group. In contrast, we did not detect IgG antibodies specific for H2B, H2A-H2B, DNA, H2A-H2B-DNA or nucleosomes in lupus dogs. There was no significant increase in an y of the IgM specificities tested. Therefore, the reactivity pattern t o nucleosome antigens in canine lupus is restricted to IgG antibodies against individual histones H1, H2A, H3 and H4. This stands in contras t with human and murine lupus, where autoantibodies are directed again st a wide variety of nucleosomal determinants, suggesting that unique mechanisms lead to the expansion of anti-histone antibody clones in ca nine lupus. The high incidence of glomerulonephritis in dog lupus sugg ests that anti-DNA antibodies are not required for the development of this complication, whereas IgG antihistone antibodies may be relevant to its pathogenesis.