Complement Activation in Patients With Probable Systemic Lupus Erythematosus and Ability to Predict Progression to American College of Rheumatology–Classified Systemic Lupus Erythematosus

Rosalind Ramsey-Goldman, Roberta Vezza Alexander, Elena M. Massarotti, Daniel J. Wallace, Sonali Narain, Cristina Arriens, Christopher E. Collins, Amit Saxena, Chaim Putterman, Kenneth C. Kalunian, Tyler O'Malley, Thierry Dervieux, Arthur Weinstein

Research output: Contribution to journalArticle

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Abstract

Objective: To evaluate the frequency of cell-bound complement activation products (CB-CAPs) as a marker of complement activation in patients with suspected systemic lupus erythematosus (SLE) and the usefulness of this biomarker as a predictor of the evolution of probable SLE into SLE as classified by the American College of Rheumatology (ACR) criteria. Methods: Patients in whom SLE was suspected by lupus experts and who fulfilled 3 ACR classification criteria for SLE (probable SLE) were enrolled, along with patients with established SLE as classified by both the ACR and the Systemic Lupus International Collaborating Clinics (SLICC) criteria, patients with primary Sjögren's syndrome (SS), and patients with other rheumatic diseases. Individual CB-CAPs were measured by flow cytometry, and positivity rates were compared to those of commonly assessed biomarkers, including serum complement proteins (C3 and C4) and autoantibodies. The frequency of a positive multianalyte assay panel (MAP), which includes CB-CAPs, was also evaluated. Probable SLE cases were followed up prospectively. Results: The 92 patients with probable SLE were diagnosed more recently than the 53 patients with established SLE, and their use of antirheumatic medications was lower. At the enrollment visit, more patients with probable SLE were positive for CB-CAPs (28%) or MAP (40%) than had low complement levels (9%) (P = 0.0001 for each). In probable SLE, MAP scores of >0.8 at enrollment predicted fulfillment of a fourth ACR criterion within 18 months (hazard ratio 3.11, P < 0.01). Conclusion: Complement activation occurs in some patients with probable SLE and can be detected with higher frequency by evaluating CB-CAPs and MAP than by assessing traditional serum complement protein levels. A MAP score above 0.8 predicts transition to classifiable SLE according to ACR criteria.

Original languageEnglish (US)
JournalArthritis and Rheumatology
DOIs
StateAccepted/In press - Jan 1 2019

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Complement Activation
Systemic Lupus Erythematosus
Rheumatology
Blood Proteins
Complement System Proteins
Complement C9
Biomarkers
Complement C4
Complement C3
Rheumatic Diseases
Autoantibodies
Flow Cytometry

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Complement Activation in Patients With Probable Systemic Lupus Erythematosus and Ability to Predict Progression to American College of Rheumatology–Classified Systemic Lupus Erythematosus. / Ramsey-Goldman, Rosalind; Alexander, Roberta Vezza; Massarotti, Elena M.; Wallace, Daniel J.; Narain, Sonali; Arriens, Cristina; Collins, Christopher E.; Saxena, Amit; Putterman, Chaim; Kalunian, Kenneth C.; O'Malley, Tyler; Dervieux, Thierry; Weinstein, Arthur.

In: Arthritis and Rheumatology, 01.01.2019.

Research output: Contribution to journalArticle

Ramsey-Goldman, R, Alexander, RV, Massarotti, EM, Wallace, DJ, Narain, S, Arriens, C, Collins, CE, Saxena, A, Putterman, C, Kalunian, KC, O'Malley, T, Dervieux, T & Weinstein, A 2019, 'Complement Activation in Patients With Probable Systemic Lupus Erythematosus and Ability to Predict Progression to American College of Rheumatology–Classified Systemic Lupus Erythematosus', Arthritis and Rheumatology. https://doi.org/10.1002/art.41093
Ramsey-Goldman, Rosalind ; Alexander, Roberta Vezza ; Massarotti, Elena M. ; Wallace, Daniel J. ; Narain, Sonali ; Arriens, Cristina ; Collins, Christopher E. ; Saxena, Amit ; Putterman, Chaim ; Kalunian, Kenneth C. ; O'Malley, Tyler ; Dervieux, Thierry ; Weinstein, Arthur. / Complement Activation in Patients With Probable Systemic Lupus Erythematosus and Ability to Predict Progression to American College of Rheumatology–Classified Systemic Lupus Erythematosus. In: Arthritis and Rheumatology. 2019.
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abstract = "Objective: To evaluate the frequency of cell-bound complement activation products (CB-CAPs) as a marker of complement activation in patients with suspected systemic lupus erythematosus (SLE) and the usefulness of this biomarker as a predictor of the evolution of probable SLE into SLE as classified by the American College of Rheumatology (ACR) criteria. Methods: Patients in whom SLE was suspected by lupus experts and who fulfilled 3 ACR classification criteria for SLE (probable SLE) were enrolled, along with patients with established SLE as classified by both the ACR and the Systemic Lupus International Collaborating Clinics (SLICC) criteria, patients with primary Sj{\"o}gren's syndrome (SS), and patients with other rheumatic diseases. Individual CB-CAPs were measured by flow cytometry, and positivity rates were compared to those of commonly assessed biomarkers, including serum complement proteins (C3 and C4) and autoantibodies. The frequency of a positive multianalyte assay panel (MAP), which includes CB-CAPs, was also evaluated. Probable SLE cases were followed up prospectively. Results: The 92 patients with probable SLE were diagnosed more recently than the 53 patients with established SLE, and their use of antirheumatic medications was lower. At the enrollment visit, more patients with probable SLE were positive for CB-CAPs (28{\%}) or MAP (40{\%}) than had low complement levels (9{\%}) (P = 0.0001 for each). In probable SLE, MAP scores of >0.8 at enrollment predicted fulfillment of a fourth ACR criterion within 18 months (hazard ratio 3.11, P < 0.01). Conclusion: Complement activation occurs in some patients with probable SLE and can be detected with higher frequency by evaluating CB-CAPs and MAP than by assessing traditional serum complement protein levels. A MAP score above 0.8 predicts transition to classifiable SLE according to ACR criteria.",
author = "Rosalind Ramsey-Goldman and Alexander, {Roberta Vezza} and Massarotti, {Elena M.} and Wallace, {Daniel J.} and Sonali Narain and Cristina Arriens and Collins, {Christopher E.} and Amit Saxena and Chaim Putterman and Kalunian, {Kenneth C.} and Tyler O'Malley and Thierry Dervieux and Arthur Weinstein",
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T1 - Complement Activation in Patients With Probable Systemic Lupus Erythematosus and Ability to Predict Progression to American College of Rheumatology–Classified Systemic Lupus Erythematosus

AU - Ramsey-Goldman, Rosalind

AU - Alexander, Roberta Vezza

AU - Massarotti, Elena M.

AU - Wallace, Daniel J.

AU - Narain, Sonali

AU - Arriens, Cristina

AU - Collins, Christopher E.

AU - Saxena, Amit

AU - Putterman, Chaim

AU - Kalunian, Kenneth C.

AU - O'Malley, Tyler

AU - Dervieux, Thierry

AU - Weinstein, Arthur

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: To evaluate the frequency of cell-bound complement activation products (CB-CAPs) as a marker of complement activation in patients with suspected systemic lupus erythematosus (SLE) and the usefulness of this biomarker as a predictor of the evolution of probable SLE into SLE as classified by the American College of Rheumatology (ACR) criteria. Methods: Patients in whom SLE was suspected by lupus experts and who fulfilled 3 ACR classification criteria for SLE (probable SLE) were enrolled, along with patients with established SLE as classified by both the ACR and the Systemic Lupus International Collaborating Clinics (SLICC) criteria, patients with primary Sjögren's syndrome (SS), and patients with other rheumatic diseases. Individual CB-CAPs were measured by flow cytometry, and positivity rates were compared to those of commonly assessed biomarkers, including serum complement proteins (C3 and C4) and autoantibodies. The frequency of a positive multianalyte assay panel (MAP), which includes CB-CAPs, was also evaluated. Probable SLE cases were followed up prospectively. Results: The 92 patients with probable SLE were diagnosed more recently than the 53 patients with established SLE, and their use of antirheumatic medications was lower. At the enrollment visit, more patients with probable SLE were positive for CB-CAPs (28%) or MAP (40%) than had low complement levels (9%) (P = 0.0001 for each). In probable SLE, MAP scores of >0.8 at enrollment predicted fulfillment of a fourth ACR criterion within 18 months (hazard ratio 3.11, P < 0.01). Conclusion: Complement activation occurs in some patients with probable SLE and can be detected with higher frequency by evaluating CB-CAPs and MAP than by assessing traditional serum complement protein levels. A MAP score above 0.8 predicts transition to classifiable SLE according to ACR criteria.

AB - Objective: To evaluate the frequency of cell-bound complement activation products (CB-CAPs) as a marker of complement activation in patients with suspected systemic lupus erythematosus (SLE) and the usefulness of this biomarker as a predictor of the evolution of probable SLE into SLE as classified by the American College of Rheumatology (ACR) criteria. Methods: Patients in whom SLE was suspected by lupus experts and who fulfilled 3 ACR classification criteria for SLE (probable SLE) were enrolled, along with patients with established SLE as classified by both the ACR and the Systemic Lupus International Collaborating Clinics (SLICC) criteria, patients with primary Sjögren's syndrome (SS), and patients with other rheumatic diseases. Individual CB-CAPs were measured by flow cytometry, and positivity rates were compared to those of commonly assessed biomarkers, including serum complement proteins (C3 and C4) and autoantibodies. The frequency of a positive multianalyte assay panel (MAP), which includes CB-CAPs, was also evaluated. Probable SLE cases were followed up prospectively. Results: The 92 patients with probable SLE were diagnosed more recently than the 53 patients with established SLE, and their use of antirheumatic medications was lower. At the enrollment visit, more patients with probable SLE were positive for CB-CAPs (28%) or MAP (40%) than had low complement levels (9%) (P = 0.0001 for each). In probable SLE, MAP scores of >0.8 at enrollment predicted fulfillment of a fourth ACR criterion within 18 months (hazard ratio 3.11, P < 0.01). Conclusion: Complement activation occurs in some patients with probable SLE and can be detected with higher frequency by evaluating CB-CAPs and MAP than by assessing traditional serum complement protein levels. A MAP score above 0.8 predicts transition to classifiable SLE according to ACR criteria.

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