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Association of Blood Concentrations of Complement Split Product iC 3b and Serum C3 With Systemic Lupus Erythematosus Disease Activity
Author(s) -
Kim Alfred H. J.,
Strand Vibeke,
Sen Deepali P.,
Fu Qiang,
Mathis Nancy L.,
Schmidt Martin J.,
Bruchas Robin R.,
Staten Nick R.,
Olson Paul K.,
Stiening Chad M.,
Atkinson John P.
Publication year - 2019
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40747
Subject(s) - medicine , prednisone , ic3b , systemic lupus erythematosus , immunology , rheumatology , erythrocyte sedimentation rate , lupus erythematosus , anti dsdna antibodies , antibody , gastroenterology , complement system , disease
Objective To examine correlations between blood levels of complement split product iC 3b and serum component C3 with clinically meaningful changes in disease activity in patients with systemic lupus erythematosus ( SLE ). Methods A total of 159 consecutive patients with SLE , diagnosed according to the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria, were enrolled in CASTLE (Complement Activation Signatures in Systemic Lupus Erythematosus), a prospective observational study. Patients with 1–7 study visits were included in this longitudinal analysis. In addition, 48 healthy volunteers were enrolled to establish a normal reference value for the ratio of blood iC 3b to serum C3 concentrations. Serum C3 and C4 levels were measured by nephelometry, and blood iC 3b levels were measured by a lateral flow assay. SLE disease activity was monitored with the Responder Index 50 instrument of the SLE Disease Activity Index 2000. Results Relative changes in the iC 3b:C3 ratio, levels of anti–double‐stranded DNA (anti‐ds DNA ) antibodies, and use of a supraphysiologic dose of prednisone (>7.5 mg/day) each independently correlated with SLE disease activity, as determined in multilevel multiple logistic regression analyses. Only the iC 3b:C3 ratio was significantly associated with clinically meaningful improvements in disease activity among patients with SLE who were receiving a supraphysiologic dose of prednisone. The iC 3b:C3 ratio outperformed C3 and C4 levels with regard to discriminating active SLE from inactive SLE , and major flares from no disease activity. The iC 3:C3 ratio, anti‐ds DNA antibody levels, erythrocyte sedimentation rate, and use of a supraphysiologic prednisone dose were each independently associated with the presence of lupus nephritis, whereas none of these measures was associated with SLE rash. The association of the iC 3b:C3 ratio with lupus nephritis was independent of other observed clinical manifestations. Conclusion The ratio of blood iC 3b to serum C3 concentrations correlates with the extent of SLE disease activity and with clinically meaningful changes in disease activity in patients with SLE . Furthermore, the iC 3b:C3 ratio may discriminate between active and inactive SLE , and between major flares and no active disease.