Anti-Interferon Autoantibodies in Adult-Onset Immunodeficiency Syndrome and Severe COVID-19 Infection

Chen, Longfang; Yang, Chengde; Cheng, Xiaobing

doi:10.3389/fimmu.2021.788368

Cited by 15 publications

(14 citation statements)

References 102 publications

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“…Anti-cytokine aAbs received great attention in recent years, especially in explaining the enormous phenotypic variability in infections, as well as the different incidence and inter-individual response variability. The development of several infectious diseases are described to be associated with the presence of aAbs targeting a number of cytokines [ 45 ]. Anti-IL-2 aAbs were found in patients with human immunodeficiency virus (HIV) infection [ 46 ].…”

Section: Production Of Aabsmentioning

confidence: 99%

“…When chronic, recurrent, hard-to-control, or unusually serious infections of common pathogens compared with the normal population occur, a potential deficiency in the IFN defense can be considered. Regardless of the type of IFN, the production of high titers of anti-IFN aAbs in serum interrupts the activation of the downstream response pathway through blocking the combination between IFNs and their receptor, resulting in increased infection rates [ 45 ]. Therefore, anti-IFN aAbs occur in previously healthy people who develop chronic, recurring, and difficult-to-control infections [ 45 ].…”

Section: Role Of Ifns and Anti-ifn Aabs In Infectious Diseasesmentioning

confidence: 99%

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Autoantibodies to Interferons in Infectious Diseases

Quiros-Roldan

Sottini

Signorini

et al. 2023

Viruses

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Anti-cytokine autoantibodies and, in particular, anti-type I interferons are increasingly described in association with immunodeficient, autoimmune, and immune-dysregulated conditions. Their presence in otherwise healthy individuals may result in a phenotype characterized by a predisposition to infections with several agents. For instance, anti-type I interferon autoantibodies are implicated in Coronavirus Disease 19 (COVID-19) pathogenesis and found preferentially in patients with critical disease. However, autoantibodies were also described in the serum of patients with viral, bacterial, and fungal infections not associated with COVID-19. In this review, we provide an overview of anti-cytokine autoantibodies identified to date and their clinical associations; we also discuss whether they can act as enemies or friends, i.e., are capable of acting in a beneficial or harmful way, and if they may be linked to gender or immunosenescence. Understanding the mechanisms underlying the production of autoantibodies could improve the approach to treating some infections, focusing not only on pathogens, but also on the possibility of a low degree of autoimmunity in patients.

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Section: Production Of Aabsmentioning

confidence: 99%

Section: Role Of Ifns and Anti-ifn Aabs In Infectious Diseasesmentioning

confidence: 99%

Autoantibodies to Interferons in Infectious Diseases

Quiros-Roldan

Sottini

Signorini

et al. 2023

Viruses

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“…For example, Bastard et al, have described rare functional auto-antibodies that neutralise 10ng/ml of both INF-α2 and IFN-ω at a 1:10 plasma dilution as associated with an OR of 67 (95% CI: 4–1109) predicting severe outcome ( 76 ). Their findings have been replicated in numerous independent cohorts ( 77–82 ) and ours have not, and the assay and statistical approaches differ. However, it is notable that the effect sizes are similar: adjusted OR 72 (95% CI: 9-1300) for a high M1 IgM in our study.…”

Section: Discussionmentioning

confidence: 59%

Structural epitope profiling identifies antibodies associated with critical COVID-19 and long COVID

Kearns

Badonyi

Lee

et al. 2022

Preprint

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Antibodies can have beneficial, neutral, or harmful effects so resolving an antibody repertoire to its target epitopes may explain heterogeneity in susceptibility to infectious disease. However, the three-dimensional nature of antibody-epitope interactions limits discovery of important targets. We describe and experimentally validated a computational method and synthetic biology pipeline for identifying structurally stable and functionally important epitopes from the SARS-CoV-2 proteome. We identify patterns of antibodies associated with immunopathology, including a non-isotype switching IgM response to a membrane protein epitope strongly associated with severe COVID-19 (adjusted OR 72.14, 95% CI: 9.71 - 1300.15). We suggest the mechanism is T independent B cell activation and identify persistence (> 1 year) of this response in individuals with long COVID particularly affected by fatigue and depression. These findings may have implications for the ongoing medical and public health response to the pandemic.

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“…At present, accumulated reports and studies strongly suggested that the AOIDS is highly associated with two speci c HLA class II alleles: HLA-DRB1*16:02/DQB1*05:02 and HLA-DRB1*15:02/DQB1*05:01. [6] [11] Nevertheless, the detailed mechanism by which IFN-γ contributes to the control of T. marneffei and NTM in vivo remains to be determined.…”

Section: Case Presentationmentioning

confidence: 99%

Multiple intracellular pathogen infections with ocular immune damage associated with adult-onset immunodeficiency due to anti-interferon-γ autoantibodies: A case report

Ning,

Yu,

Liang

et al. 2023

Preprint

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Background: Autoantibodies to interferon-γ（IFN-γ）can inhibit IFN-γ-dependent signal transducer and activator of transcription (STAT)1 phosphorylation thus predispose those patients with susceptibility to infections with normally considered low virulence pathogens, such as Talaromyces marneffei (TM), nontuberculous mycobacteria（NTM）and Mycobacterium tuberculosis. [1][2]But they are not as commonly associated with TM and NTM co-infected with Mycobacterium tuberculosis. Case presentation: Herein, we report a case of a middle-aged woman with a history of recurrent rash, cough, and expectoration. She was successively diagnosed with NTM, TM, and Mycobacterium tuberculosis infection and allergic conjunctivitis without conventional immunosuppression-associated factors in the past. The most conspicuous characteristics were recurrent infection and immune compromission. Conclusions: High-titer anti-IFN-γ autoantibodies (AIGAs) are strongly associated with severe and disseminated infections, such as NTM, TM and Mycobacterium tuberculosis. It is characterized by persistently elevated levels of inflammation and immunoglobin.

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Anti-Interferon Autoantibodies in Adult-Onset Immunodeficiency Syndrome and Severe COVID-19 Infection

Cited by 15 publications

References 102 publications

Autoantibodies to Interferons in Infectious Diseases

Autoantibodies to Interferons in Infectious Diseases

Structural epitope profiling identifies antibodies associated with critical COVID-19 and long COVID

Multiple intracellular pathogen infections with ocular immune damage associated with adult-onset immunodeficiency due to anti-interferon-γ autoantibodies: A case report

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