Human lupus anti-spliceosome A protein autoantibodies bind contiguous surface structures and segregate into two sequential epitope binding patterns.
High levels of anti-spliceosomal autoantibodies are commonly found in systemic lupus erythematosus (lupus) sera. We have evaluated the binding of lupus autoantibodies to octapeptides of nuclear ribonucleoprotein (nRNP) A, identified patterns of binding that vary between sera, quantified the proportion of anti-nRNP that binds individual peptides, and related these data to the partial tertiary structure of nRNP A. Anti-nRNP A-positive lupus sera share binding to eight antigenic groups of octapeptides from nRNP A. The four shared antigenic sites in the known nRNP A tertiary structure are contiguous on its surface and include surface loops between beta sheets and/or alpha helices. Anti-peptide Abs account for a significant portion of the human autoimmune response to nRNP A. Lupus sera are also obviously divisible into two subsets by their binding to nRNP A-derived peptides. Eight of the thirteen anti-nRNP A sera tested bind most of the eight common antigenic regions of nRNP A. All five sera in the other subset bind to two and only two groups of nRNP A octapeptides. Of this subset, absorption experiments show that as much as 75% of the anti-nRNP found in a patient serum is bound to these two octapeptides from nRNP A. The 70K spliceosome protein contains similar peptides that are also bound by these sera (OR=13.5, p<0.001). Lupus autoantibodies bind to peptides of nRNP A in discernibly consistent patterns that identify serologic subsets and in a manner that provides useful insights into the autoimmunity and antigenic structure of the nRNP A spliceosomal protein.
James
J A
JA
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Harley
J B
JB
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000378:metabolism*; D001323:Autoantibodies / Q000378:metabolism*; D001666:Binding Sites, Antibody; D003429:Cross Reactions; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology; D017381:Spliceosomes / Q000276:immunology*
D000954:Antigens, Surface; D001323:Autoantibodies; D000939:Epitopes; D007106:Immune Sera; D009842:Oligopeptides; D012261:Ribonucleoproteins