HLA-DRB1*0407 and *1304 are risk factors for scleroderma renal crisis

Binh Nguyen, Maureen D. Mayes, Frank C. Arnett, Deborah Del Junco, John D. Reveille, Emilio Gonzalez, Hilda T. Draeger, Marilyn Perry, Amir Hendiani, Kiran K. Anand, Shervin Assassi

Research output: Contribution to journalArticle

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Abstract

Objective To examine the predictive role of HLA genetic markers in scleroderma renal crisis (SRC), beyond the known clinical correlates, in a large population of patients with systemic sclerosis (SSc). Methods SSc patients from the Scleroderma Family Registry and DNA Repository, the Genetics versus Environment in Scleroderma Outcomes Study, and the rheumatology division registry at the University of Texas Health Science Center at Houston were included in the study. Relevant clinical data were obtained by chart review, and autoantibodies were detected utilizing commercially available kits. HLA class II genotyping was performed on extracted and purified genomic DNA. Results Overall, 1,519 SSc patients were included in the study, of whom 90 (6%) had developed SRC. Among the 90 patients with SRC, the diffuse cutaneous disease subtype was found in 76%, antitopoisomerase antibodies (antitopo) in 9%, anticentromere antibodies (ACAs) in 2%, and anti-RNA polymerase III (anti-RNAP III) in 50% of patients. In multivariate analyses of clinical and demographic parameters, diffuse disease type and anti-RNAP III were strong risk factors for the presence of SRC, whereas ACAs and antitopo were protective. In the final multivariate analysis, which included HLA alleles, HLA-DRB1*0407 (odds ratio [OR] 3.21, 95% confidence interval [95% CI] 1.27-8.08; P = 0.013) and DRB1*1304 (OR 4.51, 95% CI 1.30-15.65; P = 0.018) were identified as independent risk factors for SRC. Only 3 clinical characteristics, diffuse disease type, anti-RNAP III, and ACAs, remained significantly associated with SRC in the final model. Conclusion The results of this study suggest that DRB1*0407 and*1304 are independent risk factors, beyond the known clinical correlates, for the development of SRC.

Original languageEnglish (US)
Pages (from-to)530-534
Number of pages5
JournalArthritis and Rheumatism
Volume63
Issue number2
DOIs
StatePublished - Feb 2011

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HLA-DRB1 Chains
Kidney
RNA Polymerase III
Systemic Scleroderma
Registries
Multivariate Analysis
Odds Ratio
Confidence Intervals
Antibodies
DNA
Rheumatology
Genetic Markers
Skin Diseases
Autoantibodies
Alleles
Demography
Outcome Assessment (Health Care)
Health
Population

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Nguyen, B., Mayes, M. D., Arnett, F. C., Del Junco, D., Reveille, J. D., Gonzalez, E., ... Assassi, S. (2011). HLA-DRB1*0407 and *1304 are risk factors for scleroderma renal crisis. Arthritis and Rheumatism, 63(2), 530-534. https://doi.org/10.1002/art.30111

HLA-DRB1*0407 and *1304 are risk factors for scleroderma renal crisis. / Nguyen, Binh; Mayes, Maureen D.; Arnett, Frank C.; Del Junco, Deborah; Reveille, John D.; Gonzalez, Emilio; Draeger, Hilda T.; Perry, Marilyn; Hendiani, Amir; Anand, Kiran K.; Assassi, Shervin.

In: Arthritis and Rheumatism, Vol. 63, No. 2, 02.2011, p. 530-534.

Research output: Contribution to journalArticle

Nguyen, B, Mayes, MD, Arnett, FC, Del Junco, D, Reveille, JD, Gonzalez, E, Draeger, HT, Perry, M, Hendiani, A, Anand, KK & Assassi, S 2011, 'HLA-DRB1*0407 and *1304 are risk factors for scleroderma renal crisis', Arthritis and Rheumatism, vol. 63, no. 2, pp. 530-534. https://doi.org/10.1002/art.30111
Nguyen, Binh ; Mayes, Maureen D. ; Arnett, Frank C. ; Del Junco, Deborah ; Reveille, John D. ; Gonzalez, Emilio ; Draeger, Hilda T. ; Perry, Marilyn ; Hendiani, Amir ; Anand, Kiran K. ; Assassi, Shervin. / HLA-DRB1*0407 and *1304 are risk factors for scleroderma renal crisis. In: Arthritis and Rheumatism. 2011 ; Vol. 63, No. 2. pp. 530-534.
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abstract = "Objective To examine the predictive role of HLA genetic markers in scleroderma renal crisis (SRC), beyond the known clinical correlates, in a large population of patients with systemic sclerosis (SSc). Methods SSc patients from the Scleroderma Family Registry and DNA Repository, the Genetics versus Environment in Scleroderma Outcomes Study, and the rheumatology division registry at the University of Texas Health Science Center at Houston were included in the study. Relevant clinical data were obtained by chart review, and autoantibodies were detected utilizing commercially available kits. HLA class II genotyping was performed on extracted and purified genomic DNA. Results Overall, 1,519 SSc patients were included in the study, of whom 90 (6{\%}) had developed SRC. Among the 90 patients with SRC, the diffuse cutaneous disease subtype was found in 76{\%}, antitopoisomerase antibodies (antitopo) in 9{\%}, anticentromere antibodies (ACAs) in 2{\%}, and anti-RNA polymerase III (anti-RNAP III) in 50{\%} of patients. In multivariate analyses of clinical and demographic parameters, diffuse disease type and anti-RNAP III were strong risk factors for the presence of SRC, whereas ACAs and antitopo were protective. In the final multivariate analysis, which included HLA alleles, HLA-DRB1*0407 (odds ratio [OR] 3.21, 95{\%} confidence interval [95{\%} CI] 1.27-8.08; P = 0.013) and DRB1*1304 (OR 4.51, 95{\%} CI 1.30-15.65; P = 0.018) were identified as independent risk factors for SRC. Only 3 clinical characteristics, diffuse disease type, anti-RNAP III, and ACAs, remained significantly associated with SRC in the final model. Conclusion The results of this study suggest that DRB1*0407 and*1304 are independent risk factors, beyond the known clinical correlates, for the development of SRC.",
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T1 - HLA-DRB1*0407 and *1304 are risk factors for scleroderma renal crisis

AU - Nguyen, Binh

AU - Mayes, Maureen D.

AU - Arnett, Frank C.

AU - Del Junco, Deborah

AU - Reveille, John D.

AU - Gonzalez, Emilio

AU - Draeger, Hilda T.

AU - Perry, Marilyn

AU - Hendiani, Amir

AU - Anand, Kiran K.

AU - Assassi, Shervin

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N2 - Objective To examine the predictive role of HLA genetic markers in scleroderma renal crisis (SRC), beyond the known clinical correlates, in a large population of patients with systemic sclerosis (SSc). Methods SSc patients from the Scleroderma Family Registry and DNA Repository, the Genetics versus Environment in Scleroderma Outcomes Study, and the rheumatology division registry at the University of Texas Health Science Center at Houston were included in the study. Relevant clinical data were obtained by chart review, and autoantibodies were detected utilizing commercially available kits. HLA class II genotyping was performed on extracted and purified genomic DNA. Results Overall, 1,519 SSc patients were included in the study, of whom 90 (6%) had developed SRC. Among the 90 patients with SRC, the diffuse cutaneous disease subtype was found in 76%, antitopoisomerase antibodies (antitopo) in 9%, anticentromere antibodies (ACAs) in 2%, and anti-RNA polymerase III (anti-RNAP III) in 50% of patients. In multivariate analyses of clinical and demographic parameters, diffuse disease type and anti-RNAP III were strong risk factors for the presence of SRC, whereas ACAs and antitopo were protective. In the final multivariate analysis, which included HLA alleles, HLA-DRB1*0407 (odds ratio [OR] 3.21, 95% confidence interval [95% CI] 1.27-8.08; P = 0.013) and DRB1*1304 (OR 4.51, 95% CI 1.30-15.65; P = 0.018) were identified as independent risk factors for SRC. Only 3 clinical characteristics, diffuse disease type, anti-RNAP III, and ACAs, remained significantly associated with SRC in the final model. Conclusion The results of this study suggest that DRB1*0407 and*1304 are independent risk factors, beyond the known clinical correlates, for the development of SRC.

AB - Objective To examine the predictive role of HLA genetic markers in scleroderma renal crisis (SRC), beyond the known clinical correlates, in a large population of patients with systemic sclerosis (SSc). Methods SSc patients from the Scleroderma Family Registry and DNA Repository, the Genetics versus Environment in Scleroderma Outcomes Study, and the rheumatology division registry at the University of Texas Health Science Center at Houston were included in the study. Relevant clinical data were obtained by chart review, and autoantibodies were detected utilizing commercially available kits. HLA class II genotyping was performed on extracted and purified genomic DNA. Results Overall, 1,519 SSc patients were included in the study, of whom 90 (6%) had developed SRC. Among the 90 patients with SRC, the diffuse cutaneous disease subtype was found in 76%, antitopoisomerase antibodies (antitopo) in 9%, anticentromere antibodies (ACAs) in 2%, and anti-RNA polymerase III (anti-RNAP III) in 50% of patients. In multivariate analyses of clinical and demographic parameters, diffuse disease type and anti-RNAP III were strong risk factors for the presence of SRC, whereas ACAs and antitopo were protective. In the final multivariate analysis, which included HLA alleles, HLA-DRB1*0407 (odds ratio [OR] 3.21, 95% confidence interval [95% CI] 1.27-8.08; P = 0.013) and DRB1*1304 (OR 4.51, 95% CI 1.30-15.65; P = 0.018) were identified as independent risk factors for SRC. Only 3 clinical characteristics, diffuse disease type, anti-RNAP III, and ACAs, remained significantly associated with SRC in the final model. Conclusion The results of this study suggest that DRB1*0407 and*1304 are independent risk factors, beyond the known clinical correlates, for the development of SRC.

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