Disseminated Bacille Calmette‐Guérin infection in a patient with severe combined immunodeficiency caused by JAK3 gene mutation

Abstract

Bacille Calmette‐Guérin (BCG), a live attenuated vaccine prepared using Mycobacterium bovis, can prevent tuberculosis in children and is routinely administered to infants in China and many other countries. A serious complication following vaccination is disseminated BCG infection. The risk is greatly increased in patients with severe combined immunodeficiency disease (SCID), a syndrome characterized by deficiency of both humoral and cellular immunity. We report a case of disseminated BCG infection in an infant with SCID caused by two novel janus kinase 3 (JAK3) gene mutations.

Hemophagocytic syndrome associated with Mycobacterium bovis in a patient with X-SCID: a case report

“…On the other hand, although HPS due to non-tuberculous Mycobacteria as well as M. tuberculosis in adult have been reported, the report on HPS associated with M. bovis in children has not been reported [ 2 , 6 ]. In this case, M. bovis was detected by mNGS and PCR-RDB, which was consistent with the strain of BCG vaccination in China [ 7 ]. Thus, the infection in the boy might be caused by BCG vaccination.…”

“…Previous studies showed that tuberculosis infection caused by BCG vaccination usually occurs in immunodeficient children [7,8], especially for boys with low lymphocyte counts [9]. Due to the low lymphocyte counts, genetic analysis was performed, and the result of whole-exome sequencing confirmed the mutation in the IL2RG gene underlying X-SCID in the patient.…”

Case Report: Mutations in JAK3 causing severe combined immunodeficiency complicated by disseminated Bacille Calmette–Guérin disease and Pneumocystis pneumonia

“…Unlike X-linked g c SCID that generally affects male patients, JAK3 deficiency is autosomal recessive inheritance and affects both male and female patients (2). The patients with SCID, including JAK3 deficiency, have a noticeably high risk for severe, disseminated, and even fatal infections after inoculation of live-attenuated vaccines (5,(8)(9)(10)(11), particularly Bacille Calmette-Gueŕin (BCG), being an active attenuated Mycobacterium bovis vaccine (5,8,10,11). The incidence of disseminated BCG disease is approximately two cases per 1 million BCG-vaccinated children with a mortality rate of 80%, while the incidence of disseminated BCG disease is as high as one in every two BCG-vaccinated SCID patients (5,11).…”

“…T-B+NK± SCIDs, accounting for 67%~74% of all SCIDs, are mostly triggered by pathogenic genetic variants affecting the common gamma chain (γ c ) of interleukin 2 receptor (IL-2R), the associated downstream signaling enzyme Janus kinase 3 ( JAK3 ), or IL-7R alpha chain gene ( 2 , 5 ). As an unusual subtype comprising about 5% of all SCIDs ( 4 , 6 ), JAK3 deficiency with various JAK3 mutations has been sporadically reported globally ( 6 – 8 ). Unlike X-linked γ c SCID that generally affects male patients, JAK3 deficiency is autosomal recessive inheritance and affects both male and female patients ( 2 ).…”

“…The incidence of disseminated BCG disease is approximately two cases per 1 million BCG-vaccinated children with a mortality rate of 80%, while the incidence of disseminated BCG disease is as high as one in every two BCG-vaccinated SCID patients ( 5 , 11 ). JAK3 deficiency complicated by BCG disease after BCG vaccination has been rarely reported worldwide ( 8 , 12 , 13 ). Herein, we describe a unique case of JAK3 deficiency with two compound heterozygous JAK3 mutations complicated by disseminated BCG disease and Pneumocystis jirovecii pneumonia (PJP).…”