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

Abstract

Purpose of reviewThe 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 findingsSeveral 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.SummaryACAA 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.