40 - Autoantibody-Mediated Phenocopies of Primary Immunodeficiency Diseases

Abstract

Anticytokine autoantibodies represent an emerging mechanism underlying the pathogenesis of immune deficiency. In contrast to primary immune deficiencies caused by genetic mutations that are present from birth and tend to manifest early and irreversibly, immune deficiency resulting from anticytokine autoantibodies have a later onset and variable course. This group of diseases is characterized by the development of one or a few, high-titer, and high-affinity anticytokine autoantibodies whereby the disease manifestations are a consequence of the cytokine pathway that is inhibited. Further evidence supporting their role in pathogenesis is found in patients who have genetic defects within the same signaling pathway and have similar disease phenotypes. This chapter will outline the syndromes associated with anti–granulocyte macrophage–colony-stimulating factor (GM-CSF) autoantibodies and pulmonary alveolar proteinosis; anti–interferon (IFN)-γ autoantibodies and severe immunodeficiency; anti–interleukin (IL)-17A, anti–IL-17F, and anti–IL-22 autoantibodies and chronic mucocutaneous candidiasis; and anti–IL-6 autoantibodies and staphylococcal skin infection.