Association between anti-Sm and anti-ribosomal P protein autoantibodies in human systemic lupus erythematosus and MRL/lpr mice.
Anti-Sm and anti-ribosomal P protein antibodies show a high degree of specificity for the disease SLE. To determine whether a relationship between these two autoantibodies existed, the frequency of anti-P was determined in sera with and without anti-Sm activity. Of sera from lupus patients with anti-Sm 18/65 (28%), and 6/55 (11%) of sera without anti-Sm had anti-P as determined by an ELISA using a recombinant P2-beta-galactosidase fusion protein as Ag (p less than 0.05). The levels of anti-P were significantly higher in sera containing anti-Sm (0.37 +/- 0.45) than in sera without anti-Sm antibodies (0.18 +/- 0.20) (p less than 0.01). Similarly, a significantly higher proportion of anti-P positivity was found in autoimmune MRL/Mp-lpr/lpr mice positive for anti-Sm (11/53 = 21%) compared to age- and sex-matched mice without anti-Sm (3/53 = 6%) (p less than 0.05). The IgG subclass distributions for anti-Sm and anti-P antibodies were similar in the MRL mice (IgG2a greater than IgG2b greater than IgG3 greater than IgG1). The association did not reflect polyclonal B cell activation in a proportion of MRL mice because no significant differences were observed in anti-DNA, antichromatin or total serum IgG levels in mice with and without anti-Sm or, in mice positive for both anti-P and anti-Sm compared to mice positive for anti-Sm alone. Cross-inhibition experiments excluded the possibility that the Sm and P protein Ag shared a common epitope. Longitudinal measurement of anti-P and anti-Sm antibody levels by ELISA in three mice indicated that both antibodies first appeared at about 3 to 4 mo of age and fluctuated two- to threefold over 3 to 8 mo with independent peaks of activity. Recent observations regarding a relationship between anti-Sm and autoantibodies to other ribosomal proteins suggest that the association may be explained by an immune response to epitopes coassociated on the ribosome.
Division of Rheumatic Diseases, Cornell University Medical Center, New York 10021.
K B
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Elkon
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Bonfa
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Llovet
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Eisenberg
D000818:Animals; D001323:Autoantibodies / Q000032:analysis / Q000096:biosynthesis* / Q000145:classification; D001324:Autoantigens / Q000276:immunology*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000145:classification; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D017411:Ribonucleoproteins, Small Nuclear; D012269:Ribosomal Proteins / Q000276:immunology*; D055517:snRNP Core Proteins
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D017411:Ribonucleoproteins, Small Nuclear; D012269:Ribosomal Proteins; D055517:snRNP Core Proteins