en
Scientific article
Review
English

Anticytokine autoantibodies in infection and inflammation: an update

Published inCurrent opinion in allergy and clinical immunology, vol. 16, no. 6, p. 523-529
Publication date2016-12
Abstract

Purpose of review: Concise overview of the field of anticytokine autoantibodies with a focus on recent developments.

Recent findings: Advances in particular in the analysis of autoantibodies to IFNγ, granulocyte-macrophage colony-stimulating factor (GM-CSF) and type I IFN are presented. The target epitope for anti-IFNγ autoantibodies has been found to have high homology to a protein from Aspergillus suggesting molecular mimicry as a mechanism of breaking self-tolerance. A treatment strategy using a recombinant, epitope-depleted version of IFNγ is suggested. Autoantibodies to GM-CSF are associated with disseminated Crytococcus and Nocardia infections thus expanding the spectrum of associated diseases beyond pulmonary alveolar proteinosis. Detailed analysis of anti-GM-CSF autoantibody clones derived from pulmonary alveolar proteinosis patients show evidence of high somatic mutation suggesting T cell-dependent affinity maturation; full GM-CSF neutralization is achieved by synergistic binding of antibodies targeting various distinct noncross-reactive epitopes and leading to antigen sequestration and Fc-mediated clearance. Single mAbs in contrast may lead to higher GM-CSF bioavailability. Anti type I IFN-specific autoantibodies derived from autoimmune polyglandular syndrome type I patients are of extreme high affinity and negatively correlate with the incidence of type I diabetes and may be thus considered to be protective. Hypomorphic severe combined immune deficiency may be associated with complex anticytokine patterns and the emergence of anti type I IFN autoantibodies correlates with severe viral infection histories.

Summary: Anticytokine autoantibodies may cause susceptibility to infections. In autoimmune/autoinflammatory conditions, anticytokine autoantibodies may be protective or promote disease.

eng
Keywords
  • Animals
  • Autoantibodies / immunology
  • Autoantibodies / metabolism
  • Autoimmunity
  • Cross Reactions
  • Epitopes / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Humans
  • Infections / immunology
  • Inflammation / immunology
  • Interferons / immunology
  • Pulmonary Alveolar Proteinosis / immunology
  • Self Tolerance
Citation (ISO format)
BARCENAS-MORALES, Gabriela, JANDUS, Peter, DÖFFINGER, Rainer. Anticytokine autoantibodies in infection and inflammation: an update. In: Current opinion in allergy and clinical immunology, 2016, vol. 16, n° 6, p. 523–529. doi: 10.1097/ACI.0000000000000316
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1473-6322
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