Complement Alternative Pathway׳s Activation in Patients With Lupus Nephritis

Am J Med Sci. 2017 Mar;353(3):247-257. doi: 10.1016/j.amjms.2017.01.005. Epub 2017 Jan 13.


Objective: The aim of this study was to detect the spectrum of complement activation pathways in circulation and to assess their correlations with clinical and pathologic features in a large lupus nephritis cohort from China.

Materials and methods: Plasma levels of C1q, mannose-binding lectin, C4d, Bb, C3, C3a, C5a and soluble C5b-9 were detected by enzyme-linked immunosorbent assay in 222 patients with active biopsy-proven lupus nephritis, 34 patients with lupus nephritis at remission, 82 patients with active systemic lupus erythematosus without renal involvement and 39 normal controls. The correlations between levels of complement components and clinicopathological features of these patients were further analyzed.

Results: Plasma levels of C1q and C3 significantly decreased, and the levels of Bb, C3a, C5a and soluble C5b-9 were significantly elevated in patients with active lupus nephritis compared with those in remission, active systemic lupus erythematosus without renal involvement group and normal controls. In the lupus nephritis group, soluble C5b-9 levels were inversely correlated with C1q and C4d levels (r = -0.412, P < 0.001 and r = -0.221, P = 0.002, respectively), but more strongly correlated with the level of Bb (r = 0.546, P < 0.001). C3b, Bb and C5b-9 could colocalize on glomeruli in lupus nephritis. Plasma Bb level was significantly correlated with some renal disease activity indices and was a risk factor for renal outcomes (hazard ratio = 1.745; 95% CI: 1.106-2.754; P = 0.017) in the lupus nephritis group.

Conclusions: Our findings suggested that the activation of the complement alternative pathway might play a more important role in the pathogenesis of lupus nephritis, and factor Bb might be a useful marker for evaluating renal disease activity and outcomes.

Keywords: Alternative pathway; Complement; Lupus nephritis; Systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Complement Activation / physiology*
  • Complement C1q / analysis
  • Complement C3 / analysis
  • Complement C4 / analysis
  • Complement C5a / analysis
  • Complement Membrane Attack Complex / analysis
  • Complement Pathway, Alternative / physiology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Lupus Nephritis / blood
  • Lupus Nephritis / immunology*
  • Male
  • Mannose-Binding Lectin / blood


  • Complement C3
  • Complement C4
  • Complement Membrane Attack Complex
  • Mannose-Binding Lectin
  • Complement C1q
  • Complement C5a