Tags

Type your tag names separated by a space and hit enter

Interpretation of an Extended Autoantibody Profile in a Well-Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis.
Arthritis Rheumatol. 2015 Dec; 67(12):3234-44.AR

Abstract

OBJECTIVE

To determine the relationships between systemic sclerosis (SSc)-related autoantibodies, as well as their clinical associations, in a well-characterized Australian patient cohort.

METHODS

Serum from 505 Australian SSc patients were analyzed with a commercial line immunoassay (EuroLine; Euroimmun) for autoantibodies to centromere proteins CENP-A and CENP-B, RNA polymerase III (RNAP III; epitopes 11 and 155), the 90-kd nucleolar protein NOR-90, fibrillarin, Th/To, PM/Scl-75, PM/Scl-100, Ku, topoisomerase I (topo I), tripartite motif-containing protein 21/Ro 52, and platelet-derived growth factor receptor. Patient subgroups were identified by hierarchical clustering of the first 2 dimensions of a principal components analysis of quantitative autoantibody scores. Results were compared with detailed clinical data.

RESULTS

A total of 449 of the 505 patients were positive for at least 1 autoantibody by immunoblotting. Heatmap visualization of autoantibody scores, along with principal components analysis clustering, demonstrated strong, mutually exclusive relationships between CENP, RNAP III, and topo I. Five patient clusters were identified: CENP, RNAP III strong, RNAP III weak, topo I, and other. Clinical features associated with CENP, RNAP III, and topo I were consistent with previously published reports concerning limited cutaneous and diffuse cutaneous SSc. A novel finding was the statistical separation of RNAP III into 2 clusters. Patients in the RNAP III strong cluster had an increased risk of gastric antral vascular ectasia, but a lower risk of esophageal dysmotility. Patients in the other cluster were more likely to be male and to have a history of smoking and a history of malignancy, but were less likely to have telangiectasia, Raynaud's phenomenon, and joint contractures.

CONCLUSION

Five major autoantibody clusters with specific clinical and serologic associations were identified in Australian SSc patients. Subclassification and disease stratification using autoantibodies may have clinical utility, particularly in early disease.

Authors+Show Affiliations

Flinders University, Bedford Park, South Australia, and Commonwealth Scientific and Industrial Research Organization (CSIRO), Adelaide, South Australia, Australia.Flinders University and Flinders Medical Centre, Bedford Park, South Australia, and SA Pathology, Adelaide, South Australia, Australia.Queen Elizabeth Hospital, Woodville, South Australia, Australia.Flinders Medical Centre, Bedford Park, South Australia, Australia.Flinders Medical Centre, Bedford Park, South Australia, Australia.University of Adelaide, Adelaide, South Australia, and Queen Elizabeth Hospital, Woodville, South Australia, Australia.Menzies Institute for Medical Research, Hobart, Tasmania, Australia.Monash Health and Monash University, Melbourne, Victoria, Australia.University of Queensland, Brisbane, Queensland, Australia.Royal Perth Hospital, Perth, Western Australia, Australia.University of Adelaide, Adelaide, South Australia, and Queen Elizabeth Hospital, Woodville, South Australia, Australia.University of Melbourne and St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.St. Vincent's Hospital, Melbourne, Victoria, Australia.University of Adelaide and Royal Adelaide Hospital, Adelaide, South Australia, Australia.Flinders University and Flinders Medical Centre, Bedford Park, South Australia, and Repatriation General Hospital, Daw Park, South Australia, Australia.

Pub Type(s)

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

Language

eng

PubMed ID

26246178

Citation

Patterson, K A., et al. "Interpretation of an Extended Autoantibody Profile in a Well-Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis." Arthritis & Rheumatology (Hoboken, N.J.), vol. 67, no. 12, 2015, pp. 3234-44.
Patterson KA, Roberts-Thomson PJ, Lester S, et al. Interpretation of an Extended Autoantibody Profile in a Well-Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis. Arthritis Rheumatol. 2015;67(12):3234-44.
Patterson, K. A., Roberts-Thomson, P. J., Lester, S., Tan, J. A., Hakendorf, P., Rischmueller, M., Zochling, J., Sahhar, J., Nash, P., Roddy, J., Hill, C., Nikpour, M., Stevens, W., Proudman, S. M., & Walker, J. G. (2015). Interpretation of an Extended Autoantibody Profile in a Well-Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis. Arthritis & Rheumatology (Hoboken, N.J.), 67(12), 3234-44. https://doi.org/10.1002/art.39316
Patterson KA, et al. Interpretation of an Extended Autoantibody Profile in a Well-Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis. Arthritis Rheumatol. 2015;67(12):3234-44. PubMed PMID: 26246178.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interpretation of an Extended Autoantibody Profile in a Well-Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis. AU - Patterson,K A, AU - Roberts-Thomson,P J, AU - Lester,S, AU - Tan,J A, AU - Hakendorf,P, AU - Rischmueller,M, AU - Zochling,J, AU - Sahhar,J, AU - Nash,P, AU - Roddy,J, AU - Hill,C, AU - Nikpour,M, AU - Stevens,W, AU - Proudman,S M, AU - Walker,J G, PY - 2015/02/05/received PY - 2015/07/30/accepted PY - 2015/8/7/entrez PY - 2015/8/8/pubmed PY - 2016/3/15/medline SP - 3234 EP - 44 JF - Arthritis & rheumatology (Hoboken, N.J.) JO - Arthritis Rheumatol VL - 67 IS - 12 N2 - OBJECTIVE: To determine the relationships between systemic sclerosis (SSc)-related autoantibodies, as well as their clinical associations, in a well-characterized Australian patient cohort. METHODS: Serum from 505 Australian SSc patients were analyzed with a commercial line immunoassay (EuroLine; Euroimmun) for autoantibodies to centromere proteins CENP-A and CENP-B, RNA polymerase III (RNAP III; epitopes 11 and 155), the 90-kd nucleolar protein NOR-90, fibrillarin, Th/To, PM/Scl-75, PM/Scl-100, Ku, topoisomerase I (topo I), tripartite motif-containing protein 21/Ro 52, and platelet-derived growth factor receptor. Patient subgroups were identified by hierarchical clustering of the first 2 dimensions of a principal components analysis of quantitative autoantibody scores. Results were compared with detailed clinical data. RESULTS: A total of 449 of the 505 patients were positive for at least 1 autoantibody by immunoblotting. Heatmap visualization of autoantibody scores, along with principal components analysis clustering, demonstrated strong, mutually exclusive relationships between CENP, RNAP III, and topo I. Five patient clusters were identified: CENP, RNAP III strong, RNAP III weak, topo I, and other. Clinical features associated with CENP, RNAP III, and topo I were consistent with previously published reports concerning limited cutaneous and diffuse cutaneous SSc. A novel finding was the statistical separation of RNAP III into 2 clusters. Patients in the RNAP III strong cluster had an increased risk of gastric antral vascular ectasia, but a lower risk of esophageal dysmotility. Patients in the other cluster were more likely to be male and to have a history of smoking and a history of malignancy, but were less likely to have telangiectasia, Raynaud's phenomenon, and joint contractures. CONCLUSION: Five major autoantibody clusters with specific clinical and serologic associations were identified in Australian SSc patients. Subclassification and disease stratification using autoantibodies may have clinical utility, particularly in early disease. SN - 2326-5205 UR - https://www.unboundmedicine.com/medline/citation/26246178/Interpretation_of_an_Extended_Autoantibody_Profile_in_a_Well_Characterized_Australian_Systemic_Sclerosis__Scleroderma__Cohort_Using_Principal_Components_Analysis_ L2 - https://doi.org/10.1002/art.39316 DB - PRIME DP - Unbound Medicine ER -