Anticytokine autoantibodies leading to infection: early recognition, diagnosis and treatment options

Curr Opin Infect Dis. 2019 Aug;32(4):330-336. doi: 10.1097/QCO.0000000000000561.


Purpose of review: The current review gives a concise and updated overview of the relative new field of anticytokine autoantibodies (ACAA) and associated infections with a focus on recent findings regarding clinical manifestions, diagnostic and treatments.

Recent findings: Several recent case reports of unusual presentations of patients with neutralizing autoantibodies to IFN-γ and granulocyt macrophage colony-stimulating factor and expand the spectrum of clinical manifestations and suggest that anticytokine-mediated acquired immunodeficiency causing susceptibility to infection may be underdiagnosed. There is an expanding geographical distribution of antigranulocyt macrophage colony-stimulating factor associated Cryptococcus gattii infection. The spectrum of identified infections in patients with neutralizing antibodies to IFN-γ has a strong endemic component. Rituximab or cyclophophamide in addition to antimycobacterials could be a treatment options in refractory cases. NF-κB2 deficiency may be associated with a complex pattern of high titre neutralizing ACAA similar to autoimmune polyglandular syndrome type I and Thymoma. New technique for the detection of anticytokine antibodies are presented. Quantiferon testing, which is widely available for TB-diagnostic, may be repurposed to detect anti-IFN-γ autoantibodies. We propose that this test could be as well used to show if they are neutralizing.

Summary: ACAA are an emerging cause of acquired immunodeficiency which is likely underdiagnosed. Recent case reports document expanding spectra of clinical manifestations. NF-κB2 deficiency may be associated with a complex anti cytokine autoantibody pattern.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Neutralizing / immunology
  • Autoantibodies / adverse effects*
  • Autoantibodies / immunology
  • Cytokines / antagonists & inhibitors*
  • Cytokines / immunology
  • Disease Susceptibility* / immunology
  • Genetic Predisposition to Disease
  • Granulocyte Colony-Stimulating Factor / antagonists & inhibitors
  • Granulocyte Colony-Stimulating Factor / immunology
  • Humans
  • Infections / diagnosis*
  • Infections / etiology*
  • Infections / therapy*
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / immunology
  • Mycobacterium Infections / diagnosis
  • Mycobacterium Infections / etiology
  • Mycobacterium Infections / therapy
  • NF-kappa B / deficiency
  • Opportunistic Infections / diagnosis
  • Opportunistic Infections / etiology
  • Opportunistic Infections / therapy
  • Severity of Illness Index


  • Antibodies, Neutralizing
  • Autoantibodies
  • Cytokines
  • NF-kappa B
  • Granulocyte Colony-Stimulating Factor
  • Interferon-gamma