LN is mediated by complex interactions between pathogenic and protective autoantibodies.

Initiating antibodies include anti-DNA and anti-nucleosome, while propagating antibodies include anti-C1q opposed to protective anti-PTX3.

The hapten-carrier and the autologous-hapten hypothesis concur to nucleic acids immunogenicity and generation of anti-chromatin antibodies ​

Anti-PTX3 antibodies may play a protective role by counteracting complement activation.

Cross-reactive antibodies have not been compellingly proven to incite or maintain LN.