What is the role of autoimmunity in the pathogenesis of lupus nephritis?

Updated: Mar 04, 2019
  • Author: Lawrence H Brent, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Answer

Autoimmunity plays a major role in the pathogenesis of lupus nephritis. The immunologic mechanisms include production of autoantibodies directed against nuclear elements. The characteristics of the nephritogenic autoantibodies associated with lupus nephritis are as follows [1] :

  • Antigen specificity directed against nucleosome or double-stranded DNA (dsDNA) - Some anti-dsDNA antibodies cross-react with the glomerular basement membrane

  • Higher-affinity autoantibodies may form intravascular immune complexes, which are deposited in glomeruli

  • Cationic autoantibodies have a higher affinity for the anionic glomerular basement membrane

  • Autoantibodies of certain isotypes (immunoglobulin [Ig] G1 and IgG3) readily activate complement

These autoantibodies form pathogenic immune complexes intravascularly, which are deposited in glomeruli. Alternatively, autoantibodies may bind to antigens already located in the glomerular basement membrane, forming immune complexes in situ. Immune complexes promote an inflammatory response by activating complement and attracting inflammatory cells, including lymphocytes, macrophages, and neutrophils. [2, 3]


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