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Autoantibody responses to the "native" 52-kDa SS-A/Ro protein in neonatal lupus syndromes, systemic lupus erythematosus, and Sjogren's syndrome.
J Immunol. 1994 Apr 01; 152(7):3675-84.JI

Abstract

Abs to the 52-kDa SS-A/Ro protein are found in high prevalence in patients with Sjogren's syndrome (SS) and mothers whose children have the neonatal lupus syndrome (NLS). This study further defines the specificity of this response. By ELISA, 97% of 59 mothers of offspring with NLS had Abs to the 52-kDa recombinant protein compared with 80% in 132 non-NLS sera with anti-SS-A/Ro Abs (p < 0.004). Antigenic regions on the 52-kDa protein were evaluated by immunoprecipitation of [35S]-radiolabeled 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% of the anti-52-kDa sera tested and aa1-78 containing the zinc finger domains that was recognized by only half the sera. No sera immunoprecipitated 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 specificities, whereas asymptomatic mothers whose children had NLS comprised the only clinical group in which the majority recognized the central region of the molecule. Reactivity with both epitopes was demonstrated significantly more often in sera with high titers of Abs to the 60-kDa rSS-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-DRB1*0301, DQA1*0501, and DQB1*0201 alleles, compared with 30% of 10 that recognized only the central epitope (p < 0.02). In summary, this study demonstrates that there are at least two antigenic determinants on the 52-kDa SS-A/Ro protein, one "immunodominant" and the other recognized by a more "restricted" subset of anti-52-kDa SS-A/Ro Abs.

Authors+Show Affiliations

Department of Medicine, New York University School of Medicine, NY.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7511655

Citation

Buyon, J P., et al. "Autoantibody Responses to the "native" 52-kDa SS-A/Ro Protein in Neonatal Lupus Syndromes, Systemic Lupus Erythematosus, and Sjogren's Syndrome." Journal of Immunology (Baltimore, Md. : 1950), vol. 152, no. 7, 1994, pp. 3675-84.
Buyon JP, Slade SG, Reveille JD, et al. Autoantibody responses to the "native" 52-kDa SS-A/Ro protein in neonatal lupus syndromes, systemic lupus erythematosus, and Sjogren's syndrome. J Immunol. 1994;152(7):3675-84.
Buyon, J. P., Slade, S. G., Reveille, J. D., Hamel, J. C., & Chan, E. K. (1994). Autoantibody responses to the "native" 52-kDa SS-A/Ro protein in neonatal lupus syndromes, systemic lupus erythematosus, and Sjogren's syndrome. Journal of Immunology (Baltimore, Md. : 1950), 152(7), 3675-84.
Buyon JP, et al. Autoantibody Responses to the "native" 52-kDa SS-A/Ro Protein in Neonatal Lupus Syndromes, Systemic Lupus Erythematosus, and Sjogren's Syndrome. J Immunol. 1994 Apr 1;152(7):3675-84. PubMed PMID: 7511655.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Autoantibody responses to the "native" 52-kDa SS-A/Ro protein in neonatal lupus syndromes, systemic lupus erythematosus, and Sjogren's syndrome. AU - Buyon,J P, AU - Slade,S G, AU - Reveille,J D, AU - Hamel,J C, AU - Chan,E K, PY - 1994/4/1/pubmed PY - 1994/4/1/medline PY - 1994/4/1/entrez SP - 3675 EP - 84 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 152 IS - 7 N2 - Abs to the 52-kDa SS-A/Ro protein are found in high prevalence in patients with Sjogren's syndrome (SS) and mothers whose children have the neonatal lupus syndrome (NLS). This study further defines the specificity of this response. By ELISA, 97% of 59 mothers of offspring with NLS had Abs to the 52-kDa recombinant protein compared with 80% in 132 non-NLS sera with anti-SS-A/Ro Abs (p < 0.004). Antigenic regions on the 52-kDa protein were evaluated by immunoprecipitation of [35S]-radiolabeled 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% of the anti-52-kDa sera tested and aa1-78 containing the zinc finger domains that was recognized by only half the sera. No sera immunoprecipitated 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 specificities, whereas asymptomatic mothers whose children had NLS comprised the only clinical group in which the majority recognized the central region of the molecule. Reactivity with both epitopes was demonstrated significantly more often in sera with high titers of Abs to the 60-kDa rSS-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-DRB1*0301, DQA1*0501, and DQB1*0201 alleles, compared with 30% of 10 that recognized only the central epitope (p < 0.02). In summary, this study demonstrates that there are at least two antigenic determinants on the 52-kDa SS-A/Ro protein, one "immunodominant" and the other recognized by a more "restricted" subset of anti-52-kDa SS-A/Ro Abs. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/7511655/Autoantibody_responses_to_the_"native"_52_kDa_SS_A/Ro_protein_in_neonatal_lupus_syndromes_systemic_lupus_erythematosus_and_Sjogren's_syndrome_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&amp;pmid=7511655 DB - PRIME DP - Unbound Medicine ER -