Interferon-γ Receptor 1 Deficiency Corrected by Umbilical Cord Blood Transplantation

Mendelian susceptibility to mycobacterial disease—Challenges in hematopoietic stem cell transplantation

“…9 The interventions to reduce IFN-𝛾 levels before transplant by pretransplant immunosuppression or with antibodies to IFN-𝛾 or plasmapheresis might decrease the chance of rejection. 10 Emapalumab, a monoclonal antibody against IFN-𝛾, which was recently FDA-approved for treatment in primary hemophagocytic lymphohistiocytosis, may have a potential role in the future. 11 HSCT is a therapeutic option; however, further…”

“…Donor chimerism needs to be monitored at regular intervals, and if decreasing, donor T‐cell infusions should be considered as early as possible to maintain stable chimerism . The interventions to reduce IFN‐γ levels before transplant by pretransplant immunosuppression or with antibodies to IFN‐γ or plasmapheresis might decrease the chance of rejection . Emapalumab, a monoclonal antibody against IFN‐γ, which was recently FDA‐approved for treatment in primary hemophagocytic lymphohistiocytosis, may have a potential role in the future .…”

Mendelian susceptibility to mycobacterial diseases: state of the art

“…Hematopoietic stem cell transplantation (HSCT) is currently the only curative therapy and is often necessary for survival in those with severe forms of MSMD, such as AR complete IFN-γR1, IFN-γR2, or STAT1 deficiency, though the outcome is not satisfactory. Survival rates after HSCT with each genetic defect are reported as follows: 62.5% (10/16) for AR complete IFN-γR1 deficiency, 80% (4/5) for AR complete IFN-γR2 deficiency, and 64% (7/11) for AR complete STAT1 deficiency [29,31,38,[44][45][46][47][48][49][50][51][52][53]. Accurate genetic and cytological diagnosis is important because treatment strategy and prognosis vary depending on the disease.…”

Successful Hematopoietic Stem Cell Transplantation in a Patient with Complete IFN-γ Receptor 2 Deficiency: a Case Report and Literature Review

“…Twelve cases with IFN-γR1 deficiency who underwent HSCT have been described: 10 from matched related donors and 2 from matched unrelated donors. High mortality and high graft rejection rate were noted among this cohort with only four successful transplantations [ 9 – 14 ]. Main cause of treatment failure has been ascribed to poor engraftment related to high IFN-γ serum concentrations typically found in complete IFN-γR–deficient patients [ 23 ].…”

“…In these patients, the clinical manifestations begin in the first years of life and are characterized by severe, disseminated, and recurrent mycobacterial infectious diseases that require prolonged multiple antibiotic therapy [2,3]. Exogenous IFN-γ administration is mostly ineffective when no IFN-γ response could be achieved and therefore hemopoietic stem cell transplantation (HSCT) is the only curative intervention, although a high rate of rejection has been reported in these patients [9][10][11][12][13][14]. IFNγ-R2 deficiency is rare; the gene maps to 21q22.1-22-2.…”