title: Anticytokine autoantibodies in infection and inflammation: an update.
abstract: Concise overview of the field of anticytokine autoantibodies with a focus on recent developments.
  
  
  
  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.
  
  
  
  Anticytokine autoantibodies may cause susceptibility to infections. In autoimmune/autoinflammatory conditions, anticytokine autoantibodies may be protective or promote disease.
authors.affiliation: aLaboratorio 2 Inmunología, FES-Cuautitlán, UNAM, Mexico bService d' Allergologie et d'Immunologie, Hôpitaux Universitaires de Genève, Switzerland cDepartment of Clinical Biochemistry and Immunology, Addenbrookes Hospital dNational Institute of Health Research (NIHR), Cambridge Biomedical Reserch Centre, Cambridge, UK.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Barcenas-Morales
authors.forename: Peter
authors.initials: P
authors.lastname: Jandus
authors.forename: Rainer
authors.initials: R
authors.lastname: Döffinger
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism*; D015551:Autoimmunity; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007239:Infections / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D007372:Interferons / Q000276:immunology; D011649:Pulmonary Alveolar Proteinosis / Q000276:immunology*; D017634:Self Tolerance
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007372:Interferons