AUTOANTIBODY RESPONSES TO THE NATIVE 52-KDA SS-A RO PROTEIN IN NEONATAL LUPUS SYNDROMES, SYSTEMIC LUPUS-ERYTHEMATOSUS, AND SJOGRENS-SYNDROME/

Abs to the 52-kDa SS-A/Ro protein are found in high prevalence in pati ents with Sjogren's syndrome (SS) and mothers whose children have the neonatal lupus syndrome (NLS). This study further defines the specific ity of this response. By ELISA, 97% of 59 mothers of offspring with NL S had Abs to the 52-kDa recombinant protein compared with 80% in 132 n on-NLS sera with anti-SS-A/Ro Abs (p < 0.004). Antigenic regions on th e 52-kDa protein were evaluated by immunoprecipitation of [S-35]-radio labeled in vitro translation products. Ninety-five percent of 99 sera that contained anti-52-kDa Abs by ELISA reacted with a large fragment spanning amino acids (aa) 1-291. Two antigenic regions were identified , aa169-291 containing the leucine zipper that was recognized by 83% o f the anti-52-kDa sera tested and aa1-78 containing the zinc finger do mains that was recognized by only half the sera. No sera immunoprecipi tated this N-terminal fragment exclusively. Recognition of one or both regions was not unique to any clinical subset of patients; however, a greater number of sera from patients with SS contained both specifici ties, whereas asymptomatic mothers whose children had NLS comprised th e only clinical group in which the majority recognized the central reg ion of the molecule. Reactivity with both epitopes was demonstrated si gnificantly more often in sera with high titers of Abs to the 60-kDa r SS-A/Ro protein by ELISA in association with the anti-52-kDa response compared with anti-52-kDa responses associated with low titers of anti -60-kDa Abs (p < 0.04). Eighty-one percent of 16 sera that recognized the N-terminal epitope were from patients with the combination of HLA- DRB10307, DQA1*0501, and DQB1*0201 alleles, compared with 30% of 10 t hat recognized only the central epitope (p < 0.02). In summary, this s tudy demonstrates that there are at least two antigenic determinants o n the 52-kDa SS-A/Ro protein, one ''immunodominant'' and the other rec ognized by a more ''restricted'' subset of anti-52-kDa SS-A/Ro Abs.