Diversity of autoantibodies in avian scleroderma. An inherited fibrotic disease of White Leghorn chickens.

Abstract

University of California, Davis line 200 White Leghorn chickens develop an inherited progressive fibrotic disease that includes the appearance of antinuclear antibodies (ANA). To further characterize these ANA, serial aged line 200 birds were studied. Greater than 50% of line 200 birds develop antinuclear and anticytoplasmic antibodies; fluorescent staining patterns included cytoplasmic spider web, most prevalent at 1 mo of age, and fine speckled patterns, characteristic of chickens 6 mo and older. By enzyme-linked immunosorbent assay, 40.4% of line 200 birds were found to have antibodies to single-stranded DNA (ssDNA). In contrast, antibodies to histones, RNA, or poly A . poly U were not detected. Precipitating antibodies to saline extracts from chicken liver were noted in 33.3% of line 200 birds. Saline extracts from turkey, pheasant, and partridge liver but not rat, rabbit, or mouse tissues were also positive in immunodiffusion testing with these line 200 birds. The antigenicity of chicken liver extracts was sensitive to pronase, protease K. and pH variations greater than 10 and less than 5; however, they were resistant to trypsin. DNase. RNase, and incubation at 37 degrees C and 56 degrees C for 1 h. Cell fractionation in conjunction with column chromatographic techniques revealed that several protein antigens with apparent molecular weights in the range of 62,000-290,000 were present in cytoplasm but not in isolated nuclei. Line 200 sera were not reactive against nuclear ribonucleoprotein, Sm, Scl-70, or SS-B/La antigens. Thus, line 200 chickens develop antinuclear and anticytoplasmic antibodies at an early age, which recognize a unique group of protein antigenic determinants found only in avian species. Moreover, and of particular interest, the presence of autoantibodies to saline-extractable antigens correlated with positive ANA, antibodies in ssDNA, and to the clinical expression of disease.