Spectrum of Inborn errors of immunity in a cohort of 90 patients presenting with complications to BCG vaccination in India

Abstract

World Health Organisation recommends the practice of BCG vaccination at birth in countries which have a high incidence of tuberculosis and/or high leprosy burden. The BCG vaccination is considered safe for a competent immune system. However, in children with weakened immune systems cause of which can be primary or secondary, the vaccine may lead to side effects which can be localized or disseminated. In this study, we report a spectrum of inborn errors of immunity (IEI) commonly referred to as primary immunodeficiency disorders (PIDs) diagnosed in a large cohort of patients presenting with complications to BCG vaccination from India. Retrospective data analysis of patients referred to ICMR‐ National Institute of Immunohematology (ICMR‐NIIH) for IEI workup between 2007 and 2019 was done. IEI was identified in n = 52/90 (57.7%) patients presenting with BCG complications. Of these, n = 13(14.4%) patients were diagnosed with severe combined immune deficiency, n = 15(16.7%) with chronic granulomatous disease, n = 19(21.1%) with Inborn errors of IFN‐γ immunity, n = 4(4.4%) with Combined immunodeficiency and n = 1(1.1%) with Leucocyte Adhesion Deficiency type1. Majority of cases with BCGosis (88%) had an underlying IEI. This study strongly highlights the need for evaluation of patients with BCG complications for underlying IEI. While disseminated BCGosis strongly predicts underlying IEI, even localized persistent adenitis may be a warning sign of underlying IEI. It is also strongly recommended to record a family history of previous sibling death prior to administration of this live vaccine and deferring live vaccine till the diagnosis of IEI is ruled out in cases with a positive family history.

Vaccination for Patients with Inborn Errors of Immunity: a Nationwide Survey in Japan

“…One example is the Bacille de Calmette et Guérin (BCG) vaccine, which is not routinely administered in many Western countries, but is part of a routine schedule in Japan, where tuberculosis is an endemic disease [2]. This indicates that Japanese IEI patients are at a high risk for BCG-related infections, but although the prevalence of BCG infections has been reported in various countries [3,4], the situation for Japanese IEI patients is unknown. Furthermore, concerns regarding appropriate immunization for IEI patients are increasing, since the number of newly diagnosed IEI patients is expanding due to advances in diagnostic methods such as next generation sequencing (NGS) [5].…”

Case Report: A Case of Leukocyte Adhesion Deficiency, Type III Presenting With Impaired Platelet Function, Lymphocytosis and Granulocytosis

“…As noted above, he had received the live vaccine BCG (Bacillus Calmette-Guérin). Leucocyte adhesion deficiencies are included in the list of inborn errors of immunity (IEI) that describes complications to the BCG vaccination in India (47). In a retrospective study, inborn errors of immunity were identified in 52 of 90 (58%) individuals who had a localized or disseminated BCG complication; these disorders included LAD1 (47).…”

“…Leucocyte adhesion deficiencies are included in the list of inborn errors of immunity (IEI) that describes complications to the BCG vaccination in India (47). In a retrospective study, inborn errors of immunity were identified in 52 of 90 (58%) individuals who had a localized or disseminated BCG complication; these disorders included LAD1 (47). Although he had no evidence of BCG or TB (tuberculosis) disease, these complications (which are generally severe in infants) should be considered, especially in high TB burden countries such as India.…”

Case Report: Reactive Lymphohistiocytic Proliferation in Infant With a Novel Nonsense Variant of IL2RG Who Received BCG Vaccine

“…The clinical and pathologic data in this infant confer a predisposition to the weakly virulent mycobacteria, such as that of the BCG vaccine ( 4 ). Thus, this monogenic inherited condition provides an additional insight into the known list of MSMD (Mendelian susceptibility to mycobacterial diseases) ( 1 – 3 ). This report also advocates for modifying the current practice of early use of BCG ( 8 – 10 ).…”

“…Since 2005, this vaccine has been administered at birth to all newborns in the United Arab Emirates. Logically, this universal practice is expected to result in a number of "BCG disease, " especially in young infants with inborn error of immunity (IEI) or Mendelian susceptibility to mycobacterial diseases (MSMD) (1)(2)(3). An example of the latter entity is IMD28 (immunodeficiency 28, mycobacteriosis, autosomal recessive; MIM#614889), which results from pathogenic variants of IFNGR2 (interferon-gamma receptor 2; MIM#147569), such as c.123C>G, p.Tyr41 * (4).…”