Anti-fibrillarin antibody in African American patients with systemic sclerosis

Immunogenetics, clinical features, and survival analysis

Roozbeh Sharif, Marvin J. Fritzler, Maureen D. Mayes, Emilio Gonzalez, Terry A. McNearney, Hilda Draeger, Murray Baron, Daniel E. Furst, Dinesh K. Khanna, Deborah J. Del Junco, Jerry A. Molitor, Elena Schiopu, Kristine Phillips, James R. Seibold, Richard M. Silver, Robert W. Simms, Marilyn Perry, Carlos Rojo, Julio Charles, Xiaodong Zhou & 18 others Sandeep K. Agarwal, John D. Reveille, Shervin Assassi, Frank C. Arnett, Janet E. Pope, Janet Markland, David Robinson, Niall Jones, Nader Khalidi, Peter Docherty, Maysan Abu-Hakima, Sharon LeClercq, Evelyn Sutton, Douglas Smith, Jean Pierre Mathieu, Alejandra Masetto, Elzbieta Kaminska, Sophie Ligier

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objective. Anti-U3-RNP, or anti-fibrillarin antibodies (AFA), are detected more frequently among African American (AA) patients with systemic sclerosis (SSc) compared to other ethnic groups and are associated with distinct clinical features. We examined the immunogenetic, clinical, and survival correlates of AFA in a large group of AA patients with SSc. Methods. Overall, 278 AA patients with SSc and 328 unaffected AA controls were enrolled from 3 North American cohorts. Clinical features, autoantibody profile, and HLA class II genotyping were determined. To compare clinical manifestations, relevant clinical features were adjusted for disease duration. Cox proportional hazards regression was used to determine the effect of AFA on survival. Results. Fifty (18.5%) AA patients had AFA. After Bonferroni correction, HLA-DRB1*08:04 was associated with AFA, compared to unaffected AA controls (OR 11.5, p < 0.0001) and AFA-negative SSc patients (OR 5.2, p = 0.0002). AFA-positive AA patients had younger age of disease onset, higher frequency of digital ulcers, diarrhea, pericarditis, higher Medsger perivascular and lower Medsger lung severity indices (p = 0.004, p = 0.014, p = 0.019, p = 0.092, p = 0.006, and p = 0.016, respectively). After adjustment for age at enrollment, AFA-positive patients did not have different survival compared to patients without AFA (p = 0.493). Conclusion. Our findings demonstrate strong association between AFA and HLA-DRB1*08:04 allele in AA patients with SSc. AA SSc patients with AFA had younger age of onset, higher frequency of digital ulcers, pericarditis and severe lower gastrointestinal involvement, but less severe lung involvement compared to AA patients without AFA. Presence of AFA did not change survival. The Journal of Rheumatology

Original languageEnglish (US)
Pages (from-to)1622-1630
Number of pages9
JournalJournal of Rheumatology
Volume38
Issue number8
DOIs
StatePublished - Aug 2011

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Immunogenetics
Systemic Scleroderma
Survival Analysis
African Americans
Anti-Idiotypic Antibodies
Pericarditis
Survival
Age of Onset
fibrillarin
Ulcer
Lung
Rheumatology
Ethnic Groups
Autoantibodies
Diarrhea

Keywords

  • Anti-U3-RNP
  • Digital ulcer
  • Genisos
  • HLA-DRB1
  • Scleroderma
  • Scleroderma family registry

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

Anti-fibrillarin antibody in African American patients with systemic sclerosis : Immunogenetics, clinical features, and survival analysis. / Sharif, Roozbeh; Fritzler, Marvin J.; Mayes, Maureen D.; Gonzalez, Emilio; McNearney, Terry A.; Draeger, Hilda; Baron, Murray; Furst, Daniel E.; Khanna, Dinesh K.; Del Junco, Deborah J.; Molitor, Jerry A.; Schiopu, Elena; Phillips, Kristine; Seibold, James R.; Silver, Richard M.; Simms, Robert W.; Perry, Marilyn; Rojo, Carlos; Charles, Julio; Zhou, Xiaodong; Agarwal, Sandeep K.; Reveille, John D.; Assassi, Shervin; Arnett, Frank C.; Pope, Janet E.; Markland, Janet; Robinson, David; Jones, Niall; Khalidi, Nader; Docherty, Peter; Abu-Hakima, Maysan; LeClercq, Sharon; Sutton, Evelyn; Smith, Douglas; Mathieu, Jean Pierre; Masetto, Alejandra; Kaminska, Elzbieta; Ligier, Sophie.

In: Journal of Rheumatology, Vol. 38, No. 8, 08.2011, p. 1622-1630.

Research output: Contribution to journalArticle

Sharif, R, Fritzler, MJ, Mayes, MD, Gonzalez, E, McNearney, TA, Draeger, H, Baron, M, Furst, DE, Khanna, DK, Del Junco, DJ, Molitor, JA, Schiopu, E, Phillips, K, Seibold, JR, Silver, RM, Simms, RW, Perry, M, Rojo, C, Charles, J, Zhou, X, Agarwal, SK, Reveille, JD, Assassi, S, Arnett, FC, Pope, JE, Markland, J, Robinson, D, Jones, N, Khalidi, N, Docherty, P, Abu-Hakima, M, LeClercq, S, Sutton, E, Smith, D, Mathieu, JP, Masetto, A, Kaminska, E & Ligier, S 2011, 'Anti-fibrillarin antibody in African American patients with systemic sclerosis: Immunogenetics, clinical features, and survival analysis', Journal of Rheumatology, vol. 38, no. 8, pp. 1622-1630. https://doi.org/10.3899/jrheum.110071
Sharif, Roozbeh ; Fritzler, Marvin J. ; Mayes, Maureen D. ; Gonzalez, Emilio ; McNearney, Terry A. ; Draeger, Hilda ; Baron, Murray ; Furst, Daniel E. ; Khanna, Dinesh K. ; Del Junco, Deborah J. ; Molitor, Jerry A. ; Schiopu, Elena ; Phillips, Kristine ; Seibold, James R. ; Silver, Richard M. ; Simms, Robert W. ; Perry, Marilyn ; Rojo, Carlos ; Charles, Julio ; Zhou, Xiaodong ; Agarwal, Sandeep K. ; Reveille, John D. ; Assassi, Shervin ; Arnett, Frank C. ; Pope, Janet E. ; Markland, Janet ; Robinson, David ; Jones, Niall ; Khalidi, Nader ; Docherty, Peter ; Abu-Hakima, Maysan ; LeClercq, Sharon ; Sutton, Evelyn ; Smith, Douglas ; Mathieu, Jean Pierre ; Masetto, Alejandra ; Kaminska, Elzbieta ; Ligier, Sophie. / Anti-fibrillarin antibody in African American patients with systemic sclerosis : Immunogenetics, clinical features, and survival analysis. In: Journal of Rheumatology. 2011 ; Vol. 38, No. 8. pp. 1622-1630.
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abstract = "Objective. Anti-U3-RNP, or anti-fibrillarin antibodies (AFA), are detected more frequently among African American (AA) patients with systemic sclerosis (SSc) compared to other ethnic groups and are associated with distinct clinical features. We examined the immunogenetic, clinical, and survival correlates of AFA in a large group of AA patients with SSc. Methods. Overall, 278 AA patients with SSc and 328 unaffected AA controls were enrolled from 3 North American cohorts. Clinical features, autoantibody profile, and HLA class II genotyping were determined. To compare clinical manifestations, relevant clinical features were adjusted for disease duration. Cox proportional hazards regression was used to determine the effect of AFA on survival. Results. Fifty (18.5{\%}) AA patients had AFA. After Bonferroni correction, HLA-DRB1*08:04 was associated with AFA, compared to unaffected AA controls (OR 11.5, p < 0.0001) and AFA-negative SSc patients (OR 5.2, p = 0.0002). AFA-positive AA patients had younger age of disease onset, higher frequency of digital ulcers, diarrhea, pericarditis, higher Medsger perivascular and lower Medsger lung severity indices (p = 0.004, p = 0.014, p = 0.019, p = 0.092, p = 0.006, and p = 0.016, respectively). After adjustment for age at enrollment, AFA-positive patients did not have different survival compared to patients without AFA (p = 0.493). Conclusion. Our findings demonstrate strong association between AFA and HLA-DRB1*08:04 allele in AA patients with SSc. AA SSc patients with AFA had younger age of onset, higher frequency of digital ulcers, pericarditis and severe lower gastrointestinal involvement, but less severe lung involvement compared to AA patients without AFA. Presence of AFA did not change survival. The Journal of Rheumatology",
keywords = "Anti-U3-RNP, Digital ulcer, Genisos, HLA-DRB1, Scleroderma, Scleroderma family registry",
author = "Roozbeh Sharif and Fritzler, {Marvin J.} and Mayes, {Maureen D.} and Emilio Gonzalez and McNearney, {Terry A.} and Hilda Draeger and Murray Baron and Furst, {Daniel E.} and Khanna, {Dinesh K.} and {Del Junco}, {Deborah J.} and Molitor, {Jerry A.} and Elena Schiopu and Kristine Phillips and Seibold, {James R.} and Silver, {Richard M.} and Simms, {Robert W.} and Marilyn Perry and Carlos Rojo and Julio Charles and Xiaodong Zhou and Agarwal, {Sandeep K.} and Reveille, {John D.} and Shervin Assassi and Arnett, {Frank C.} and Pope, {Janet E.} and Janet Markland and David Robinson and Niall Jones and Nader Khalidi and Peter Docherty and Maysan Abu-Hakima and Sharon LeClercq and Evelyn Sutton and Douglas Smith and Mathieu, {Jean Pierre} and Alejandra Masetto and Elzbieta Kaminska and Sophie Ligier",
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TY - JOUR

T1 - Anti-fibrillarin antibody in African American patients with systemic sclerosis

T2 - Immunogenetics, clinical features, and survival analysis

AU - Sharif, Roozbeh

AU - Fritzler, Marvin J.

AU - Mayes, Maureen D.

AU - Gonzalez, Emilio

AU - McNearney, Terry A.

AU - Draeger, Hilda

AU - Baron, Murray

AU - Furst, Daniel E.

AU - Khanna, Dinesh K.

AU - Del Junco, Deborah J.

AU - Molitor, Jerry A.

AU - Schiopu, Elena

AU - Phillips, Kristine

AU - Seibold, James R.

AU - Silver, Richard M.

AU - Simms, Robert W.

AU - Perry, Marilyn

AU - Rojo, Carlos

AU - Charles, Julio

AU - Zhou, Xiaodong

AU - Agarwal, Sandeep K.

AU - Reveille, John D.

AU - Assassi, Shervin

AU - Arnett, Frank C.

AU - Pope, Janet E.

AU - Markland, Janet

AU - Robinson, David

AU - Jones, Niall

AU - Khalidi, Nader

AU - Docherty, Peter

AU - Abu-Hakima, Maysan

AU - LeClercq, Sharon

AU - Sutton, Evelyn

AU - Smith, Douglas

AU - Mathieu, Jean Pierre

AU - Masetto, Alejandra

AU - Kaminska, Elzbieta

AU - Ligier, Sophie

PY - 2011/8

Y1 - 2011/8

N2 - Objective. Anti-U3-RNP, or anti-fibrillarin antibodies (AFA), are detected more frequently among African American (AA) patients with systemic sclerosis (SSc) compared to other ethnic groups and are associated with distinct clinical features. We examined the immunogenetic, clinical, and survival correlates of AFA in a large group of AA patients with SSc. Methods. Overall, 278 AA patients with SSc and 328 unaffected AA controls were enrolled from 3 North American cohorts. Clinical features, autoantibody profile, and HLA class II genotyping were determined. To compare clinical manifestations, relevant clinical features were adjusted for disease duration. Cox proportional hazards regression was used to determine the effect of AFA on survival. Results. Fifty (18.5%) AA patients had AFA. After Bonferroni correction, HLA-DRB1*08:04 was associated with AFA, compared to unaffected AA controls (OR 11.5, p < 0.0001) and AFA-negative SSc patients (OR 5.2, p = 0.0002). AFA-positive AA patients had younger age of disease onset, higher frequency of digital ulcers, diarrhea, pericarditis, higher Medsger perivascular and lower Medsger lung severity indices (p = 0.004, p = 0.014, p = 0.019, p = 0.092, p = 0.006, and p = 0.016, respectively). After adjustment for age at enrollment, AFA-positive patients did not have different survival compared to patients without AFA (p = 0.493). Conclusion. Our findings demonstrate strong association between AFA and HLA-DRB1*08:04 allele in AA patients with SSc. AA SSc patients with AFA had younger age of onset, higher frequency of digital ulcers, pericarditis and severe lower gastrointestinal involvement, but less severe lung involvement compared to AA patients without AFA. Presence of AFA did not change survival. The Journal of Rheumatology

AB - Objective. Anti-U3-RNP, or anti-fibrillarin antibodies (AFA), are detected more frequently among African American (AA) patients with systemic sclerosis (SSc) compared to other ethnic groups and are associated with distinct clinical features. We examined the immunogenetic, clinical, and survival correlates of AFA in a large group of AA patients with SSc. Methods. Overall, 278 AA patients with SSc and 328 unaffected AA controls were enrolled from 3 North American cohorts. Clinical features, autoantibody profile, and HLA class II genotyping were determined. To compare clinical manifestations, relevant clinical features were adjusted for disease duration. Cox proportional hazards regression was used to determine the effect of AFA on survival. Results. Fifty (18.5%) AA patients had AFA. After Bonferroni correction, HLA-DRB1*08:04 was associated with AFA, compared to unaffected AA controls (OR 11.5, p < 0.0001) and AFA-negative SSc patients (OR 5.2, p = 0.0002). AFA-positive AA patients had younger age of disease onset, higher frequency of digital ulcers, diarrhea, pericarditis, higher Medsger perivascular and lower Medsger lung severity indices (p = 0.004, p = 0.014, p = 0.019, p = 0.092, p = 0.006, and p = 0.016, respectively). After adjustment for age at enrollment, AFA-positive patients did not have different survival compared to patients without AFA (p = 0.493). Conclusion. Our findings demonstrate strong association between AFA and HLA-DRB1*08:04 allele in AA patients with SSc. AA SSc patients with AFA had younger age of onset, higher frequency of digital ulcers, pericarditis and severe lower gastrointestinal involvement, but less severe lung involvement compared to AA patients without AFA. Presence of AFA did not change survival. The Journal of Rheumatology

KW - Anti-U3-RNP

KW - Digital ulcer

KW - Genisos

KW - HLA-DRB1

KW - Scleroderma

KW - Scleroderma family registry

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