A concise review of the area of anticytokine autoantibodies, with an emphasis on recent advances. There are specific advances in the study of autoantibodies to IFN, granulocyte-macrophage colony-stimulating factor (GM-CSF), and type I IFN. The target epitope for anti-IFN autoantibodies was discovered to have strong similarity to an Aspergillus protein, implying molecular mimicry as a mechanism for breaking self-tolerance. A therapeutic approach based on recombinant, epitope-depleted IFN is proposed. Autoantibodies to GM-CSF have been linked to widespread Crytococcus and Nocardia infections, broadening the range of illnesses associated with them beyond pulmonary alveolar proteinosis. Anti-GM-CSF autoantibody clones derived from patients with pulmonary alveolar proteinosis show evidence of high somatic mutation, indicating T cell-dependent affinity maturation; full GM-CSF neutralization is achieved by synergistic binding of antibodies targeting various distinct non cross-reactive epitopes, leading to antigen sequestration and Fc-mediated clearance. GM-CSF bioavailability may be increased using single mAbs. Anti-type I IFN-specific autoantibodies generated from individuals with autoimmune polyglandular syndrome type I have a very high affinity and a negative correlation with the occurrence of type I diabetes, and may thus be considered protective. Hypomorphic severe combined immune deficiency may be linked with complicated anticytokine patterns, and the development of anti type I IFN autoantibodies is related with a history of severe viral infection.
Autoantibodies against anti cytokines may increase susceptibility to infections. Anti Cytokine autoantibodies can either prevent or exacerbate illness in autoimmune/autoinflammatory diseases.