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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.

Association of Blood Concentrations of Complement Split Product iC3b and Serum C3 With Systemic Lupus Erythematosus Disease Activity

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  • Medientyp: E-Artikel
  • Titel: Association of Blood Concentrations of Complement Split Product iC3b and Serum C3 With Systemic Lupus Erythematosus Disease Activity
  • Beteiligte: 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.
  • Erschienen: Wiley, 2019
  • Erschienen in: Arthritis & Rheumatology
  • Sprache: Englisch
  • DOI: 10.1002/art.40747
  • ISSN: 2326-5191; 2326-5205
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec><jats:title>Objective</jats:title><jats:p>To examine correlations between blood levels of complement split product <jats:styled-content style="fixed-case">iC</jats:styled-content>3b and serum component C3 with clinically meaningful changes in disease activity in patients with systemic lupus erythematosus (<jats:styled-content style="fixed-case">SLE</jats:styled-content>).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A total of 159 consecutive patients with <jats:styled-content style="fixed-case">SLE</jats:styled-content>, diagnosed according to the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria, were enrolled in <jats:styled-content style="fixed-case">CASTLE</jats:styled-content> (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 <jats:styled-content style="fixed-case">iC</jats:styled-content>3b to serum C3 concentrations. Serum C3 and C4 levels were measured by nephelometry, and blood <jats:styled-content style="fixed-case">iC</jats:styled-content>3b levels were measured by a lateral flow assay. <jats:styled-content style="fixed-case">SLE</jats:styled-content> disease activity was monitored with the Responder Index 50 instrument of the <jats:styled-content style="fixed-case">SLE</jats:styled-content> Disease Activity Index 2000.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Relative changes in the <jats:styled-content style="fixed-case">iC</jats:styled-content>3b:C3 ratio, levels of anti–double‐stranded <jats:styled-content style="fixed-case">DNA</jats:styled-content> (anti‐ds<jats:styled-content style="fixed-case">DNA</jats:styled-content>) antibodies, and use of a supraphysiologic dose of prednisone (&gt;7.5 mg/day) each independently correlated with <jats:styled-content style="fixed-case">SLE</jats:styled-content> disease activity, as determined in multilevel multiple logistic regression analyses. Only the <jats:styled-content style="fixed-case">iC</jats:styled-content>3b:C3 ratio was significantly associated with clinically meaningful improvements in disease activity among patients with <jats:styled-content style="fixed-case">SLE</jats:styled-content> who were receiving a supraphysiologic dose of prednisone. The <jats:styled-content style="fixed-case">iC</jats:styled-content>3b:C3 ratio outperformed C3 and C4 levels with regard to discriminating active <jats:styled-content style="fixed-case">SLE</jats:styled-content> from inactive <jats:styled-content style="fixed-case">SLE</jats:styled-content>, and major flares from no disease activity. The <jats:styled-content style="fixed-case">iC</jats:styled-content>3:C3 ratio, anti‐ds<jats:styled-content style="fixed-case">DNA</jats:styled-content> 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 <jats:styled-content style="fixed-case">SLE</jats:styled-content> rash. The association of the <jats:styled-content style="fixed-case">iC</jats:styled-content>3b:C3 ratio with lupus nephritis was independent of other observed clinical manifestations.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The ratio of blood <jats:styled-content style="fixed-case">iC</jats:styled-content>3b to serum C3 concentrations correlates with the extent of <jats:styled-content style="fixed-case">SLE</jats:styled-content> disease activity and with clinically meaningful changes in disease activity in patients with <jats:styled-content style="fixed-case">SLE</jats:styled-content>. Furthermore, the <jats:styled-content style="fixed-case">iC</jats:styled-content>3b:C3 ratio may discriminate between active and inactive <jats:styled-content style="fixed-case">SLE</jats:styled-content>, and between major flares and no active disease.</jats:p></jats:sec>
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