The role of IgG4 in systemic lupus erythematosus: Implications for pathogenesis and therapy

Immunoglobulin (Ig) G4 has a distinctive nature, and its involvement in autoimmune disorders is a subject of ongoing debate and uncertainty. A growing body of evidence indicates that IgG4 may play a pathogenic role in the development of systemic lupus erythematosus (SLE). The IgG4 autoantibodies have the capability to bind autoantigens in a competitive manner with other Ig classes, thereby forming immune complexes (ICs) that are noninflammatory in nature. This is due to the low affinity of IgG4 for both the Fc receptors and the C1 complement molecule, which results in a diminished inflammatory response in individuals with SLE. The present study aims to elucidate the significance of IgG4 in SLE. The present discourse pertains to the nascent and suggested modalities through which IgG4 might participate in the pathogenesis of SLE and the potential ramifications for therapeutic interventions in SLE. The activation of effector function is contingent upon the ability of each autoreactive IgG subtype to induce the inflammatory response during the progression of SLE. Autoantigens can be bound entirely by IgG4 autoantibodies, along with other subclasses of autoantibodies like IgG1, IgG2, and IgG3, resulting in the formation of immune complexes between autoantibodies and autoantigens. The structural composition of the hinge region in IgG4 is distinctive and is responsible for its restricted capacity to initiate effector function. In comparison to other subcategories of autoantibodies, it is plausible that IgG4 autoantibodies may mitigate the advancement of SLE by impeding complement depletion and the generation of inflammatory cytokines.image