Diagnostic and therapeutic challenges in a child with complete interferon-γ receptor 1 deficiency

Abstract

Autosomal recessive (AR) complete Interferon-γ Receptor1 (IFN-γR1) deficiency is a rare variant of Mendelian susceptibility to mycobacterial disease (MSMD). Although hematopoietic stem cell transplantation (HSCT) remains the only curative treatment, outcomes are heterogeneous; delayed engraftment and/or graft rejection being commonly observed. This case report and literature review expands the knowledge about this rare but potentially fatal pathology, providing details regarding diagnosis, antimicrobial treatment, transplant performance, and outcome that may help to guide physicians caring for patients with AR complete IFN-γR1 or IFN-γR2 deficiency.

Keywords: atypical mycobacteria; infant; interferon gamma receptor; primary immunodeficiency; transplantation.

Figure 1. Clinical presentation

Marked lymphadenopathies (A, B) and generalized macupapular rash affecting torso and lower extremities (C, D).

Figure 2. Cytokine responses to IFN-γ stimulation and expression of IFN-γR1 prior and after HSCT

(A) IL-12p70 production in vitro in response to lipopolysaccharide plus various concentrations of IFN-γ before HSCT. The patient is represented by triangles and a healthy control (HC) with squares. (B) Expression of IFN-γR1 before HSCT. Whole blood from the patient and from one HC was stained with two IFN-γR1-specific mAbs (dark gray; GIR94 and GIR208) and isotypic control antibodies (pale gray). (C) IL-12p70 production in vitro response to lipopolysaccharide plus various concentrations of IFN-γ after HSCT as described in (A). (D) Expression of IFN-γR1 after HSCT. Whole blood from the patient and from a HC was stained with two IFN-γR1-specific mAbs as done in (B). CD14+ monocytes, CD15+ granulocytes and CD19+ B cells were analyzed.