Presence of plasma complement regulatory proteins clusterin (Apo J) and vitronectin (S40) on circulating immune

A K Chauhan1, T L Moore

  • 1ProGen Biologics, Wildwood, MO 63021, USA. anil@progenbiologics.com

Insights

Complement regulatory proteins clusterin and vitronectin bind to the membrane attack complex (MAC) and prevent cell damage. Higher levels on MAC bound to immune complexes correlate with kidney involvement in systemic lupus erythematosus (SLE) patients.

Area of Science:

  • Immunology
  • Complement system
  • Protein interactions

Background:

  • Complement regulatory (CR) proteins, clusterin and vitronectin, inhibit the membrane attack complex (MAC)-induced cytolysis.
  • The role of these CR proteins in the context of circulating immune complexes (CIC) and disease pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the presence and quantity of clusterin and vitronectin on MAC bound to CIC (MAC-CIC) in systemic lupus erythematosus (SLE) patients.
  • To correlate the levels of these proteins with soluble MAC (SMAC) and clinical manifestations, particularly renal involvement.

Main Methods:

  • Quantification of clusterin and vitronectin on SMAC and MAC-CIC using antibodies against polymerized C9.
  • Analysis of plasma samples from SLE patients.

Main Results:

  • A strong correlation was observed between the quantities of SMAC and MAC-CIC.
  • Clusterin and vitronectin levels were two- to threefold higher on MAC-CIC compared to SMAC.
  • Elevated levels of clusterin and vitronectin were associated with renal involvement in SLE patients.

Conclusions:

  • Clusterin and vitronectin are present on MAC associated with CIC in SLE patients.
  • These CR proteins may play a significant role beyond MAC regulation in SLE pathogenesis, potentially contributing to renal disease.

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