Anticytokine autoantibodies in infection and inflammation: an update.

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.

• Authors: Gabriela Barcenas-Morales, Peter Jandus, Rainer Döffinger
• Journal: Current opinion in allergy and clinical immunology (Curr Opin Allergy Clin Immunol) Vol. 16 Issue 6 Pg. 523-529 (12 2016) ISSN: 1473-6322 [Electronic] United States
• PMID: 27755185 (Publication Type: Journal Article, Review)

Chemical References

• Autoantibodies
• Epitopes
• Granulocyte-Macrophage Colony-Stimulating Factor
• Interferons

Topics

• Animals
• Autoantibodies (immunology, 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