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Multicenter Study
. 2020 Apr;7(1):e000377.
doi: 10.1136/lupus-2019-000377.

Cell-bound complement activation products associate with lupus severity in SLE

Cristina Arriens  1   2 , Roberta Vezza Alexander  3 , Sonali Narain  4 , Amit Saxena  5 , Christopher E Collins  6 , Daniel J Wallace  7 , Elena Massarotti  8 , John Conklin  9 , Kenneth C Kalunian  10 , Chaim Putterman  11   12   13 , Rosalind Ramsey-Goldman  14 , Jill P Buyon  15 , Anca Askanase  16 , Richard A Furie  4 , Judith A James  1   2 , Ghalib A Bello  1 , Susan Manzi  17 , Joseph Ahearn  17 , Tyler O'Malley  9 , Arthur Weinstein  9 , Thierry Dervieux  9
Affiliations
Multicenter Study

Cell-bound complement activation products associate with lupus severity in SLE

Cristina Arriens et al. Lupus Sci Med. 2020 Apr.

Abstract

Objectives: To evaluate the association between lupus severity and cell-bound complement activation products (CB-CAPs) or low complement proteins C3 and C4.

Methods: All subjects (n=495) fulfilled the American College of Rheumatology (ACR) classification criteria for SLE. Abnormal CB-CAPs (erythrocyte-bound C4d or B-lymphocyte-bound C4d levels >99th percentile of healthy) and complement proteins C3 and C4 were determined using flow cytometry and turbidimetry, respectively. Lupus severity was estimated using the Lupus Severity Index (LSI). Statistical analysis consisted of multivariable linear regression and groups comparisons.

Results: Abnormal CB-CAPs were more prevalent than low complement values irrespective of LSI levels (62% vs 38%, respectively, p<0.0001). LSI was low (median 5.44, IQR: 4.77-6.93) in patients with no complement abnormality, intermediate in patients with abnormal CB-CAPs (median 6.09, IQR: 5.31-8.20) and high in the group presenting with both abnormal CB-CAPs and low C3 and/or C4 (median 7.85, IQR: 5.51-8.37). Odds of immunosuppressant use was higher in subjects with LSI ≥5.95 compared with subjects with LSI <5.95 (1.60 vs 0.53, p<0.0001 for both). Multivariable regression analysis revealed that higher LSI scores associated with abnormal CB-CAPs-but not low C3/C4-after adjusting for younger age, race and longer disease duration (p=0.0001), which were also independent predictors of disease severity (global R2=0.145).

Conclusion: Abnormalities in complement activation as measured by CB-CAPs are associated with increased LSI.

Keywords: SLE; autoimmune diseases; disease activity.

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Conflict of interest statement

Competing interests: RVA, JC, TO and TD are current or former employees of Exagen. AW is a consultant to Exagen and chief medical officer. CA, SN, AS, CEC, DJW, EM, KCK, CP, RR-G, JPB, AA, RF, SM, JA have received research support from Exagen.

Figures

Figure 1
Figure 1
Comparison of low complement and elevated cell-bound complement activation products (CB-CAPs) by Lupus Severity Index (LSI) group. Percentage of subjects with low complement (low serum complement proteins C3 and/or C4) and elevated CB-CAPs (elevated EC4d and/or BC4d) by LSI groups.
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