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. 2022 Apr 4;219(4):e20211387.
doi: 10.1084/jem.20211387. Epub 2022 Mar 23.

Human autoantibodies underlying infectious diseases

Anne Puel  1   2   3 , Paul Bastard  1   2   3   4 , Jacinta Bustamante  1   2   3   5 , Jean-Laurent Casanova  1   2   3   4   6
Affiliations

Human autoantibodies underlying infectious diseases

Anne Puel et al. J Exp Med. .

Abstract

The vast interindividual clinical variability observed in any microbial infection-ranging from silent infection to lethal disease-is increasingly being explained by human genetic and immunological determinants. Autoantibodies neutralizing specific cytokines underlie the same infectious diseases as inborn errors of the corresponding cytokine or response pathway. Autoantibodies against type I IFNs underlie COVID-19 pneumonia and adverse reactions to the live attenuated yellow fever virus vaccine. Autoantibodies against type II IFN underlie severe disease caused by environmental or tuberculous mycobacteria, and other intra-macrophagic microbes. Autoantibodies against IL-17A/F and IL-6 are less common and underlie mucocutaneous candidiasis and staphylococcal diseases, respectively. Inborn errors of and autoantibodies against GM-CSF underlie pulmonary alveolar proteinosis; associated infections are less well characterized. In individual patients, autoantibodies against cytokines preexist infection with the pathogen concerned and underlie the infectious disease. Human antibody-driven autoimmunity can interfere with cytokines that are essential for protective immunity to specific infectious agents but that are otherwise redundant, thereby underlying specific infectious diseases.

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Conflict of interest statement

Disclosures: J.-L. Casanova is an inventor on patent application PCT/US2021/042741, filed July 22, 2021, submitted by The Rockefeller University that covers diagnosis of susceptibility to, and treatment of, viral disease and viral vaccines, including Covid-19 and vaccine-associated diseases. No other disclosures were reported.

Figures

Figure 1.
Figure 1.
Human inborn errors of and auto-Abs to cytokines underlying infectious diseases. This figure illustrates the key actions of four of the cytokines reviewed in this article. Gene products mutated in patients with infectious diseases are shown in red. Auto-Abs neutralizing the cytokines are also shown. For the sake of simplicity, only the most important cell types involved in the biology of each of these cytokines are shown. Molecules, including cytokines and their receptors, are also shown only on key cell types. A more detailed description of the biology of each cytokine can be found in specific reviews.
See this image and copyright information in PMC

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