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

• Published in: Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2020-01, Vol.72 (1), p.78-88
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anti-Citrullinated Protein Antibodies - immunology; Antibodies, Antinuclear - immunology; Autoantibodies; Autoantibodies - immunology; B-Lymphocytes - metabolism; Biomarkers; Case-Control Studies; Cell activation; Chronic conditions; Complement; Complement activation; Complement Activation - immunology; Complement C3 - immunology; Complement C4 - immunology; Complement C4b - immunology; Complement C4b - metabolism; Complement component C3; Complement component C4; Criteria; Disease Progression; Erythrocytes - metabolism; Evaluation; Female; Flow Cytometry; Humans; Lupus; Lupus Erythematosus, Systemic - immunology; Male; Middle Aged; Original; Peptide Fragments - immunology; Peptide Fragments - metabolism; Prospective Studies; Proteins; Rheumatic diseases; Rheumatic Diseases - immunology; Rheumatoid Factor - immunology; Rheumatology; Sjogren's syndrome; Sjogren's Syndrome - immunology; Systemic Lupus Erythematosus; Young Adult
• ISSN: 2326-5191; 2326-5205
• DOI: 10.1002/art.41093

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.