Dimeric and polymeric IgA, but not monomeric IgA, enhance the production of IL-6 by human renal mesangial cells

T J F Reterink,M R Daha,L A Van Es,W E M Schroeijers

doi:10.1155/s0962935196000269

Abstract

Depositions of IgA in the renal glomerular mesangial area are a hallmark of IgA nephropathy, and are thought to be crucial for the onset of inflammation processes in IgA nephropathy. In this report we show that human mesangial cells (MC) in vitro bind IgA and that binding of IgA enhances the production of IL-6 by MC. Furthermore we show that the size of IgA is crucial in its capability to enhance IL-6 production. Monomeric IgA does not affect basic IL-6 production, whereas dimeric and polymeric IgA enhance IL-6 production up to 3- to 9-fold respectively. Additional studies demonstrate that enhanced IL-6 production by MC is not accompanied by increased proliferation of human mesangial cells, a finding which is distinct from that found with rat mesangial cells. Taken together, these fmdings suggest that deposition of dimeric and polymeric IgA in the mesangial area of human kidneys in IgA nephropathy may amplify local inflammation.

Highlights

Immunoglobulin A (IgA) is the predominant immunoglobulin in human secretions and the second most important immunoglobulin in the circulation on a quantitative basis.1’2 Depositions of IgA in the glomerular mesangial area of the kidney, as found in IgA nephropathy, are thought to play a crucial role in the inflammatory processes in this disease
It is interesting that phagocytic blood cells of patients with IgA nephropathy seem to be hampered in CD89mediated clearance of IgA.[10]
Human dimeric IgA was able to bind to mesengial cells (MC) in a dosedependent manner

Summary

Introduction

Immunoglobulin A (IgA) is the predominant immunoglobulin in human secretions and the second most important immunoglobulin in the circulation on a quantitative basis.1’2 Depositions of IgA in the glomerular mesangial area of the kidney, as found in IgA nephropathy, are thought to play a crucial role in the inflammatory processes in this disease. A delayed clearance of IgA has been suggested. A specific receptor for IgA was described in rat and human renal glomerular mesangial cells (CD89).[9] It is not known whether CD89 plays a role in IgA deposition in the kidney during IgA nephropathy. It is interesting that phagocytic blood cells of patients with IgA nephropathy seem to be hampered in CD89mediated clearance of IgA.[10]

Methods

Results

Conclusion