Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features

Melissa E. Munroe, Kendra A. Young, Diane L. Kamen, Joel M. Guthridge, Timothy B. Niewold, Karen H. Costenbader, Michael H. Weisman, Mariko L. Ishimori, Daniel J. Wallace, Gary S. Gilkeson, David R. Karp, John B. Harley, Jill M. Norris, Judith A. James

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective: Systemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential for curtailing irreversible inflammatory damage. The aim of this study was to identify factors associated with transition to classified disease that would inform our understanding of the risk of SLE. Methods: Previously identified blood relatives of patients with SLE, who had <4 American College of Rheumatology (ACR) classification criteria for SLE at baseline, were enrolled in this follow-up study (n = 409 unaffected relatives). Participants provided detailed family, demographic, and clinical information, including the SLE-specific portion of the Connective Tissue Disease Screening Questionnaire (SLE-CSQ). Serum and plasma samples were tested for the presence of lupus-associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEEs) were applied to identify factors predictive of disease transition. Results: Of the 409 unaffected relatives of SLE patients, 45 (11%) had transitioned to classified SLE at follow-up (mean time to follow-up 6.4 years). Relatives who transitioned to SLE displayed more lupus-associated autoantibody specificities and higher SLE-CSQ scores (P < 0.0001) at baseline than did relatives who did not transition. Importantly, those who had developed SLE during the follow-up period also had elevated baseline plasma levels of inflammatory mediators, including B lymphocyte stimulator, stem cell factor (SCF), and interferon-associated chemokines (P ≤ 0.02), with concurrent decreases in the levels of regulatory mediators, transforming growth factor β (TGFβ), and interleukin-10 (P ≤ 0.03). GEE analyses revealed that baseline SLE-CSQ scores or ACR scores (number of ACR criteria satisfied) and plasma levels of SCF and TGFβ, but not autoantibodies, were significant and independent predictors of SLE transition (P ≤ 0.03). Conclusion: Preclinical alterations in levels of soluble mediators may predict transition to classified disease in relatives of SLE patients. Thus, immune perturbations precede SLE classification and can help identify high-risk relatives for rheumatology referral and potential enrollment in prevention trials.

Original languageEnglish (US)
Pages (from-to)630-642
Number of pages13
JournalArthritis and Rheumatology
Volume69
Issue number3
DOIs
StatePublished - Mar 1 2017

Fingerprint

Systemic Lupus Erythematosus
Rheumatology
Autoantibodies
Stem Cell Factor
Transforming Growth Factors
B-Cell Activating Factor
Connective Tissue Diseases
Chemokines
Interleukin-10
Interferons
Autoimmune Diseases
Referral and Consultation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Munroe, M. E., Young, K. A., Kamen, D. L., Guthridge, J. M., Niewold, T. B., Costenbader, K. H., ... James, J. A. (2017). Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features. Arthritis and Rheumatology, 69(3), 630-642. https://doi.org/10.1002/art.40004

Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features. / Munroe, Melissa E.; Young, Kendra A.; Kamen, Diane L.; Guthridge, Joel M.; Niewold, Timothy B.; Costenbader, Karen H.; Weisman, Michael H.; Ishimori, Mariko L.; Wallace, Daniel J.; Gilkeson, Gary S.; Karp, David R.; Harley, John B.; Norris, Jill M.; James, Judith A.

In: Arthritis and Rheumatology, Vol. 69, No. 3, 01.03.2017, p. 630-642.

Research output: Contribution to journalArticle

Munroe, ME, Young, KA, Kamen, DL, Guthridge, JM, Niewold, TB, Costenbader, KH, Weisman, MH, Ishimori, ML, Wallace, DJ, Gilkeson, GS, Karp, DR, Harley, JB, Norris, JM & James, JA 2017, 'Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features', Arthritis and Rheumatology, vol. 69, no. 3, pp. 630-642. https://doi.org/10.1002/art.40004
Munroe, Melissa E. ; Young, Kendra A. ; Kamen, Diane L. ; Guthridge, Joel M. ; Niewold, Timothy B. ; Costenbader, Karen H. ; Weisman, Michael H. ; Ishimori, Mariko L. ; Wallace, Daniel J. ; Gilkeson, Gary S. ; Karp, David R. ; Harley, John B. ; Norris, Jill M. ; James, Judith A. / Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features. In: Arthritis and Rheumatology. 2017 ; Vol. 69, No. 3. pp. 630-642.
@article{8696708c6b2943cc9c3d836530d6926a,
title = "Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features",
abstract = "Objective: Systemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential for curtailing irreversible inflammatory damage. The aim of this study was to identify factors associated with transition to classified disease that would inform our understanding of the risk of SLE. Methods: Previously identified blood relatives of patients with SLE, who had <4 American College of Rheumatology (ACR) classification criteria for SLE at baseline, were enrolled in this follow-up study (n = 409 unaffected relatives). Participants provided detailed family, demographic, and clinical information, including the SLE-specific portion of the Connective Tissue Disease Screening Questionnaire (SLE-CSQ). Serum and plasma samples were tested for the presence of lupus-associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEEs) were applied to identify factors predictive of disease transition. Results: Of the 409 unaffected relatives of SLE patients, 45 (11{\%}) had transitioned to classified SLE at follow-up (mean time to follow-up 6.4 years). Relatives who transitioned to SLE displayed more lupus-associated autoantibody specificities and higher SLE-CSQ scores (P < 0.0001) at baseline than did relatives who did not transition. Importantly, those who had developed SLE during the follow-up period also had elevated baseline plasma levels of inflammatory mediators, including B lymphocyte stimulator, stem cell factor (SCF), and interferon-associated chemokines (P ≤ 0.02), with concurrent decreases in the levels of regulatory mediators, transforming growth factor β (TGFβ), and interleukin-10 (P ≤ 0.03). GEE analyses revealed that baseline SLE-CSQ scores or ACR scores (number of ACR criteria satisfied) and plasma levels of SCF and TGFβ, but not autoantibodies, were significant and independent predictors of SLE transition (P ≤ 0.03). Conclusion: Preclinical alterations in levels of soluble mediators may predict transition to classified disease in relatives of SLE patients. Thus, immune perturbations precede SLE classification and can help identify high-risk relatives for rheumatology referral and potential enrollment in prevention trials.",
author = "Munroe, {Melissa E.} and Young, {Kendra A.} and Kamen, {Diane L.} and Guthridge, {Joel M.} and Niewold, {Timothy B.} and Costenbader, {Karen H.} and Weisman, {Michael H.} and Ishimori, {Mariko L.} and Wallace, {Daniel J.} and Gilkeson, {Gary S.} and Karp, {David R.} and Harley, {John B.} and Norris, {Jill M.} and James, {Judith A.}",
year = "2017",
month = "3",
day = "1",
doi = "10.1002/art.40004",
language = "English (US)",
volume = "69",
pages = "630--642",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

TY - JOUR

T1 - Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features

AU - Munroe, Melissa E.

AU - Young, Kendra A.

AU - Kamen, Diane L.

AU - Guthridge, Joel M.

AU - Niewold, Timothy B.

AU - Costenbader, Karen H.

AU - Weisman, Michael H.

AU - Ishimori, Mariko L.

AU - Wallace, Daniel J.

AU - Gilkeson, Gary S.

AU - Karp, David R.

AU - Harley, John B.

AU - Norris, Jill M.

AU - James, Judith A.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Objective: Systemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential for curtailing irreversible inflammatory damage. The aim of this study was to identify factors associated with transition to classified disease that would inform our understanding of the risk of SLE. Methods: Previously identified blood relatives of patients with SLE, who had <4 American College of Rheumatology (ACR) classification criteria for SLE at baseline, were enrolled in this follow-up study (n = 409 unaffected relatives). Participants provided detailed family, demographic, and clinical information, including the SLE-specific portion of the Connective Tissue Disease Screening Questionnaire (SLE-CSQ). Serum and plasma samples were tested for the presence of lupus-associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEEs) were applied to identify factors predictive of disease transition. Results: Of the 409 unaffected relatives of SLE patients, 45 (11%) had transitioned to classified SLE at follow-up (mean time to follow-up 6.4 years). Relatives who transitioned to SLE displayed more lupus-associated autoantibody specificities and higher SLE-CSQ scores (P < 0.0001) at baseline than did relatives who did not transition. Importantly, those who had developed SLE during the follow-up period also had elevated baseline plasma levels of inflammatory mediators, including B lymphocyte stimulator, stem cell factor (SCF), and interferon-associated chemokines (P ≤ 0.02), with concurrent decreases in the levels of regulatory mediators, transforming growth factor β (TGFβ), and interleukin-10 (P ≤ 0.03). GEE analyses revealed that baseline SLE-CSQ scores or ACR scores (number of ACR criteria satisfied) and plasma levels of SCF and TGFβ, but not autoantibodies, were significant and independent predictors of SLE transition (P ≤ 0.03). Conclusion: Preclinical alterations in levels of soluble mediators may predict transition to classified disease in relatives of SLE patients. Thus, immune perturbations precede SLE classification and can help identify high-risk relatives for rheumatology referral and potential enrollment in prevention trials.

AB - Objective: Systemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential for curtailing irreversible inflammatory damage. The aim of this study was to identify factors associated with transition to classified disease that would inform our understanding of the risk of SLE. Methods: Previously identified blood relatives of patients with SLE, who had <4 American College of Rheumatology (ACR) classification criteria for SLE at baseline, were enrolled in this follow-up study (n = 409 unaffected relatives). Participants provided detailed family, demographic, and clinical information, including the SLE-specific portion of the Connective Tissue Disease Screening Questionnaire (SLE-CSQ). Serum and plasma samples were tested for the presence of lupus-associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEEs) were applied to identify factors predictive of disease transition. Results: Of the 409 unaffected relatives of SLE patients, 45 (11%) had transitioned to classified SLE at follow-up (mean time to follow-up 6.4 years). Relatives who transitioned to SLE displayed more lupus-associated autoantibody specificities and higher SLE-CSQ scores (P < 0.0001) at baseline than did relatives who did not transition. Importantly, those who had developed SLE during the follow-up period also had elevated baseline plasma levels of inflammatory mediators, including B lymphocyte stimulator, stem cell factor (SCF), and interferon-associated chemokines (P ≤ 0.02), with concurrent decreases in the levels of regulatory mediators, transforming growth factor β (TGFβ), and interleukin-10 (P ≤ 0.03). GEE analyses revealed that baseline SLE-CSQ scores or ACR scores (number of ACR criteria satisfied) and plasma levels of SCF and TGFβ, but not autoantibodies, were significant and independent predictors of SLE transition (P ≤ 0.03). Conclusion: Preclinical alterations in levels of soluble mediators may predict transition to classified disease in relatives of SLE patients. Thus, immune perturbations precede SLE classification and can help identify high-risk relatives for rheumatology referral and potential enrollment in prevention trials.

UR - http://www.scopus.com/inward/record.url?scp=85014073019&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014073019&partnerID=8YFLogxK

U2 - 10.1002/art.40004

DO - 10.1002/art.40004

M3 - Article

VL - 69

SP - 630

EP - 642

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 3

ER -