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

Tovo, Pier-Angelo; Garazzino, Silvia; Saglio, Francesco; Scolfaro, Carlo; Bustamante, Jacinta; Badolato, Raffaele

doi:10.1007/s10875-020-00855-x

Cited by 10 publications

(5 citation statements)

References 26 publications

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“…Identification of a molecular defect can help us to take therapeutic management decisions. Patients with complete IFN-γR1, IFN-γR2, and STAT1 deficiencies can be cured with HSCT ( 35 ). Majority of our patients were treated with 4 drug ATT as is the usual practice in our country, the duration of treatment ranging from 6 months to 2 years depending on the site of involvement and the clinical response to treatment.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India

et al. 2021

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Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), Salmonella, fungi, parasites like Leishmania and some viruses, in otherwise healthy individuals. Mutations in the IL12RB1 gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with Salmonella and non-typhi Salmonella (13%), Cytomegalovirus (CMV) (11%), Candida (7%), NTM (4%), and Histoplasma (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.

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Section: Discussionmentioning

confidence: 99%

Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India

et al. 2021

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“…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.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Mendelian susceptibility to mycobacterial diseases: state of the art

Noma

Mizoguchi

Tsumura

et al. 2022

Clinical Microbiology and Infection

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“…Adjuvant therapy with recombinant interferon-gamma (rIFN-γ) has shown to be effective in BCG-osis associated with some types of MSMD and chronic granulomatous disease (CGD) [ 9 , 10 ]. In patients diagnosed with autosomal recessive (AR) complete IFN-γ receptor 1 or 2 deficiency (or AR STAT1 deficiency) or SCID with available matched donors, allogenic hematopoietic stem cell transplantation (HSCT) can be a curative option [ 4 , 11 ]. However, in MSMD patients, due to the recurrent infections and high serum levels of IFN-γ, the HSCT may lead to unfavorable outcomes [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Effective anti-mycobacterial treatment for BCG disease in patients with Mendelian Susceptibility to Mycobacterial Disease (MSMD): a case series

Mahdaviani

Fallahi

Jamee

et al. 2022

Ann Clin Microbiol Antimicrob

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Background Post-vaccination BCG disease typically attests to underlying inborn errors of immunity (IEIs), with the highest rates of complications in patients with Mendelian susceptibility to mycobacterial disease (MSMD). However, therapeutic protocols for the management of BCG-osis (disseminated) and persistent BCG-itis (localized) are still controversial. Methods Twenty-four Iranian patients with MSMD (BCG-osis or BCG-itis), followed from 2009 to 2020 in Tehran, were included in the study. Their medical records were retrospectively reviewed for demographics, clinical features, laboratory findings, and molecular diagnosis. The therapeutic protocol sheets were prepared to contain the types and duration of anti-mycobacterial agents. Results BCG disease either as BCG-itis (33.3%) or BCG-osis (66.7%) was confirmed in all patients by positive gastric washing test (54.2%), microbial smear and culture (58.3%), or purified protein derivative (PPD) test (4.2%). The duration between BCG-osis onset and MSMD diagnosis was 21.6 months. All except three patients were initiated on second-line anti-mycobacterial agents with either a fluoroquinolone (levofloxacin: 15 mg/kg/day, ciprofloxacin: 20 mg/kg/day, ofloxacin: 15 mg/kg/day), aminoglycoside (amikacin: 10–15 mg/kg/day, streptomycin: 15 mg/kg/day), and/or macrolide (clarithromycin: 15 mg/kg/day) along with oral rifampin (10 mg/kg/day), isoniazid (15 mg/kg/day), and ethambutol (20 mg/kg/day). Three patients showed a clinical response to rifampin, despite in vitro resistance. Fourteen (58.3%) patients received also adjuvant subcutaneous IFN-γ therapy, 50 µ/m2 every other day. At the end of survey, most patients (n = 22, 91.7%) were alive and two patients died following BCG-osis and respiratory failure. Conclusions We recommend the early instigation of second-line anti-mycobacterial agents in MSMD patients with BCG disease.

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

Cited by 10 publications

References 26 publications

Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India

Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India

Mendelian susceptibility to mycobacterial diseases: state of the art

Effective anti-mycobacterial treatment for BCG disease in patients with Mendelian Susceptibility to Mycobacterial Disease (MSMD): a case series

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