Clinical and Genetic Characteristics of BCG Disease in Chinese Children: a Retrospective Study

Abstract

Summarize the characteristics of the largest cohort of BCG disease and compare differences in clinical characteristics and outcomes among different genotypes and between primary immunode ciency disease (PID) and non-PID patients. MethodsWe collected information on patients with BCG disease in our center from January 2015 to December 2020 and divided them into four groups: chronic granulomatous disease (CGD), Mendelian susceptibility to mycobacterial disease (MSMD), severe combined immunode ciency disease (SCID) and unspeci ed pathogenic group. ResultsA total of 134 patients were reviewed, and most of them had PID. A total of 112 (83.6%) patients had 19 different types of pathogenic gene mutations, most of whom (91.1%) were classi ed with CGD, MSMD and SCID. CYBB was the most common gene mutation (53/112). BCG disease behaves differently in individuals with different PIDs. Signi cant differences in sex (P < 0.001), age at diagnosis (P = 0.019), frequency of recurrent fever (P = 0.003) and infection severity (P = 0.038) were noted among the four groups. The CGD group had the highest rate of males and the oldest age at diagnosis. The MSMD group had the highest probability of disseminated infection (46.4%). The course of anti-tuberculosis treatment and the survival time between PID and non-PID patients were similar. ConclusionGreater than 80% of BCG patients have PID; accordingly, gene sequencing should be performed in patients with BCG disease for early diagnosis. BCG disease behaves differently in patients with different types of PID. Non-PID patients had similar outcomes to PID patients, which hints that they may have pathogenic gene mutations that need to be discovered. tend to suffer from BCG disease with an incidence of approximately 1:10,000-1:1,000,000 or even disseminated BCG disease, which is a rare and serious adverse reaction [4] . In 2015, Aishwarya Venkataraman et al. observed sixty children who presented with adverse reactions and found that twothirds (65%) presented with BCG lymphadenitis, one-third (30%) presented with injection site complications, and 54% had received anti-tuberculous therapy and/or a procedure [5] . With the increasing use of gene sequencing, some pathogenic genes have been discovered in some BCG diseases [6] . Rina Yue Ling Ong et al. reported that 10 patients likely had underlying PID -four with SCID, three with MSMD, one with anhidrotic ectodermal dysplasia with PID (EDA-ID), one with combined immunode ciency (CID), and one with a STAT-1 gain-of-function mutation [7] . A previous study enrolled 74 con rmed cases of BCGosis/BCGitis in our center in 2014. Thirty-two patients (43.2%) had de nitive PID, and CGD was the most common PID (n = 23, accounting for 71.9% of all PID patients) [6] .However, limited updated clinical data on large-sized samples of BCG disease have been reported, and differences among different genotypes and between PID and non-PID patients have not been described.This study aims to analyze the clinical and genetic characteristics of the largest cohort of BCG...

Inborn errors of immunity in mainland China: the past, present and future

“…Early screening of newborns not only improves diagnostic rates and outcomes for IEI but also helps avoid vaccinerelated adverse events for several IEI entities. [13][14][15] The maturation processes of T cells and B cells produce T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles, respectively, which can be used for newborn screening of congenital T cell or/ and B cell deficiencies.…”

“…For example, the lack of a national newborn screening (NBS) programme leads to delayed diagnosis, severe complications and adverse reactions to vaccines in some types of IEIs. [13][14][15] In addition, although there is a relatively large number of patients with IEI, the discovery of novel disease-causing genes in mainland China lags behind that of developed countries. 1 6 Herein, we reviewed the development and current state of IEI in mainland China, highlighting the achievements made, as well as the opportunities and challenges that lie ahead.…”