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Reactivity with dichotomous determinants of Ro 60 stratifies autoantibody responses in lupus and primary Sjögren's syndrome.
Arthritis Rheum. 2010 May; 62(5):1448-56.AR

Abstract

OBJECTIVE

Analysis of B cell determinants of Ro 60 exposed on the surface of apoptotic cells (apotopes) or intracellular epitopes provides insight into the structural forms of the autoantigen that break immune tolerance. This study was initiated to compare anti-Ro 60 responses in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS) against membrane-bound and intracellular forms of Ro 60.

METHODS

The reactivity of autoantibodies from patients with SLE and primary SS to Ro 60 apotopes and epitopes was assessed by multiparameter flow cytometry and solid-phase immunoassay. Anti-Ro 60 IgG was eluted from early apoptotic cells or recombinant Ro 60 immobilized on nitrocellulose, and binding to membrane-bound and intracellular forms of Ro 60 was quantitated by flow cytometry.

RESULTS

An immunodominant apotope, which was recognized by IgG from a subset of SLE patients with anti-Ro, but not anti-La, autoantibodies, was mapped to a region forming a helix-loop-helix at the apical tip of the Ro 60 molecule. Immobilization of this region to the solid phase exposed an epitope that was recognized by IgG from primary SS and SLE patients whose sera had both anti-Ro and anti-La autoantibodies. Autoantibodies eluted from either the surface of apoptotic cells or the Ro 60 epitope on the solid phase were non-cross-reactive and specifically recognized membrane-bound or cytoplasmic forms of Ro 60.

CONCLUSION

This is the first example of a dichotomy of human autoantibody responses against mutually exclusive determinants linked to a single domain of a systemic autoantigen and supports a model in which tolerance is broken by different immunogenic forms of Ro 60.

Authors+Show Affiliations

Flinders Medical Centre, Bedford Park, South Australia, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20131295

Citation

Reed, Joanne H., et al. "Reactivity With Dichotomous Determinants of Ro 60 Stratifies Autoantibody Responses in Lupus and Primary Sjögren's Syndrome." Arthritis and Rheumatism, vol. 62, no. 5, 2010, pp. 1448-56.
Reed JH, Dudek NL, Osborne SE, et al. Reactivity with dichotomous determinants of Ro 60 stratifies autoantibody responses in lupus and primary Sjögren's syndrome. Arthritis Rheum. 2010;62(5):1448-56.
Reed, J. H., Dudek, N. L., Osborne, S. E., Kaufman, K. M., Jackson, M. W., Purcell, A. W., & Gordon, T. P. (2010). Reactivity with dichotomous determinants of Ro 60 stratifies autoantibody responses in lupus and primary Sjögren's syndrome. Arthritis and Rheumatism, 62(5), 1448-56. https://doi.org/10.1002/art.27370
Reed JH, et al. Reactivity With Dichotomous Determinants of Ro 60 Stratifies Autoantibody Responses in Lupus and Primary Sjögren's Syndrome. Arthritis Rheum. 2010;62(5):1448-56. PubMed PMID: 20131295.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reactivity with dichotomous determinants of Ro 60 stratifies autoantibody responses in lupus and primary Sjögren's syndrome. AU - Reed,Joanne H, AU - Dudek,Nadine L, AU - Osborne,Shannon E, AU - Kaufman,Kenneth M, AU - Jackson,Michael W, AU - Purcell,Anthony W, AU - Gordon,Tom P, PY - 2010/2/5/entrez PY - 2010/2/5/pubmed PY - 2010/6/15/medline SP - 1448 EP - 56 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 62 IS - 5 N2 - OBJECTIVE: Analysis of B cell determinants of Ro 60 exposed on the surface of apoptotic cells (apotopes) or intracellular epitopes provides insight into the structural forms of the autoantigen that break immune tolerance. This study was initiated to compare anti-Ro 60 responses in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS) against membrane-bound and intracellular forms of Ro 60. METHODS: The reactivity of autoantibodies from patients with SLE and primary SS to Ro 60 apotopes and epitopes was assessed by multiparameter flow cytometry and solid-phase immunoassay. Anti-Ro 60 IgG was eluted from early apoptotic cells or recombinant Ro 60 immobilized on nitrocellulose, and binding to membrane-bound and intracellular forms of Ro 60 was quantitated by flow cytometry. RESULTS: An immunodominant apotope, which was recognized by IgG from a subset of SLE patients with anti-Ro, but not anti-La, autoantibodies, was mapped to a region forming a helix-loop-helix at the apical tip of the Ro 60 molecule. Immobilization of this region to the solid phase exposed an epitope that was recognized by IgG from primary SS and SLE patients whose sera had both anti-Ro and anti-La autoantibodies. Autoantibodies eluted from either the surface of apoptotic cells or the Ro 60 epitope on the solid phase were non-cross-reactive and specifically recognized membrane-bound or cytoplasmic forms of Ro 60. CONCLUSION: This is the first example of a dichotomy of human autoantibody responses against mutually exclusive determinants linked to a single domain of a systemic autoantigen and supports a model in which tolerance is broken by different immunogenic forms of Ro 60. SN - 1529-0131 UR - https://www.unboundmedicine.com/medline/citation/20131295/Reactivity_with_dichotomous_determinants_of_Ro_60_stratifies_autoantibody_responses_in_lupus_and_primary_Sjögren's_syndrome_ L2 - https://doi.org/10.1002/art.27370 DB - PRIME DP - Unbound Medicine ER -