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

Abstract

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.

Anti-IL6 Autoantibodies in an Infant With CRP-Less Septic Shock

“…For example, an increased susceptibility to weakly virulent mycobacteria due to IFN-γ autoAbs resembles a rare PID called Mendelian susceptibility to mycobacterial diseases due to monogenic defects in IL-12/IFN-γ circuit. Similarly, abs against Th17-related cytokines IL-17A, IL-17F, IL-22, IL-23 underlie increased susceptibility to fungal infections resembling chronic mucocutaneous candidiasis due to various genetic etiologies [reviewed in (15)].…”

Clinical findings of Talaromyces marneffei infection among patients with anti-interferon-γ immunodeficiency: a prospective cohort study

“…In group 3, only two patients were anti-IFN-γ autoAb-positive, possibly because cryptococcal infection is associated with other anti-cytokine antibodies. A recent study also con rmed the link between the presence of neutralizing anti-granulocyte macrophage colony stimulating factor autoAbs and cerebral cryptococcosis, particularly that caused by C. gattii infection [22].…”

Anticorps anti-cytokines : quel impact clinique en pathologie humaine ?

“…Ils doivent ainsi être recherchés en cas d'infection inhabituelle (agents infectieux concernés détaillés dans la Fig. 1), inexpliquée et débutant à l'âge adulte (il s'agit de « phénocopies » auto-immunes, et donc acquises au cours de la vie, de déficits immunitaires héréditaires d'origine génétique concernant ces mêmes cytokines ou leurs récepteurs, commenc¸ ant quant à elles généralement tôt dans la vie, à un âge pédiatrique) [2].…”