Hanna IJspeert, Netherlands
Erasmus MC ImmunologyPresenter of 1 Presentation
ANTI-INTERFERON GAMMA AND IL-17 AUTOANTIBODIES IN A CHILD WITH ULCERATION AFTER BACILLUS CALMETTE-GUERIN (BCG) VACCINATION AND ONYCHOMYCOSIS
Abstract
Background and Aims
Anti-cytokine autoantibodies (ACAAs) neutralize cytokines and are therefore an important mechanism of disease pathogenesis. Neutralizing anti-IFNγ autoantibodies result in susceptibility to mycobacterial and intracellular infections, and high titers of these autoantibodies are associated with adult-onset immunodeficiency in the South-East Asian population. Anti-IL-17A, IL-17-F, IL-22 and IFNα autoantibodies have been associated with chronic mucocutaneous candidiasis, and are found in nearly all patients with autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED), while ACAA directed to IFNα a.o. can also be present in patients with hypomorphic RAG mutations. Here we present an Indonesian boy, born in 2016, with recurrent eczema and onychomycosis, who developed an ulcer of 3cm at the site of the injection 3 weeks after BCG vaccination. The aim of this study is to determine if ACAA are the underlying mechanism causing the onychomycosis and the atypical response to the BCG vaccination.
Methods
serum ACAA were measured in the patient serum using a Luminex based in-house assay and compared to data from the child’s parents, an APECED patient and a healthy control.
Results
The patient was positive for ACAA against IFNγ, -IL-17A and to a lesser extend IL-17F. ACAA against IL-22, IFN-α were not detected. The pattern differed from APECED where high levels of anti-IL17A, IL-17F, IL-22 and IFNα were detected, with low levels anti-IFNγ autoantibodies.
Conclusions
To our knowledge this is the first child positive for anti-IFNγ autoantibodies. The anti-IFNγ and anti-IL-17A autoantibodies might explain the clinical phenotype, which we are currently exploring along with exome sequencing to identify a potential genetic defect.