Secondary immunodeficiencies related to the presence of anti-cytokine autoantibodies

Anti-cytokine autoantibodies (ACAA) have been reported to be an important cause of secondary immunodeficiencies. High titers of neutralizing autoantibodies may cause susceptibility to different life-threatening infectious diseases. For example, neutralizing autoantibodies against IFN gamma have been reported to be correlated with susceptibility to mycobacterial infections and intracellular fungal pathogens. Autoantibodies against IL-6 were detected in patients with subcutaneous abscesses and recur-rent staphylococcal cellulitis; on the other hand, patients with cryptococcosis, nocardiosis, and pulmonary alveolar proteinosis were positive for autoantibodies to GM-CSF. A relationship has also been established between autoantibodies against IL-17 and IL-22 and chronic mucosal Candida infections, which have been identified in patients with APECED or thymoma. Autoan-tibodies against type-I IFN have been recently reported during the onset of acute COVID-19. These ACAAs resemble genetic defects in cytokines or their signaling pathways. Therefore, they may be considered to be primary immunodeficiencies phenocopies. Consequently, the detection of ACAA could be important in the diagnosis of patients, particularly in the case of late-onset diseases, in order to decide appropriate treatments. This review presents an overview of current understanding of ACAA-associated secondary immunodeficiencies.

Automated summary

Anti-cytokine autoantibodies (ACAA) are an important cause of secondary immunodeficiencies, and high titers of these autoantibodies can lead to susceptibility to life-threatening infectious diseases. Various types of autoantibodies have been associated with specific infections, such as IFN gamma autoantibodies with mycobacterial infections and IL-6 autoantibodies with subcutaneous abscesses. Detection of ACAA is crucial for the diagnosis and treatment of patients, especially those with late-onset diseases.