RESUMO
BCG disease has been reported in primary and secondary immunodeficiency and as Mendelian Susceptibility to Mycobacterial Diseases (MSMD). Investigation of this syndrome has led to the identifications of a series of genetic, inherited defects in the IL-12/IFN-γ axis. MSMD-causing mutations have been found in seven autosomal and two X-linked genes. In these patients, local or disseminated vaccine BCG infections are common. We report a clinical series including two infants with left axillary adenitis ipsilateral to the site of neonatal BCG immunization; one of them member of a family with two previously reported cases and a single sporadic case. All of them were diagnosed sequentially in Puerto Montt, Chile. The aim of this report is to notify the first Chilean disseminated BCG patients without previous immunodeficiency, in whom it was possible to identify an underlying immunodeficiency, although specific tests for IL-12/IFN-γ axis was no performed in our country. Clinical suspicion and international collaboration permitted to confirm IL12-Rβ1 deficiency in 2 of 3 familial cases and a sporadic case.
La enfermedad por el bacilo de Calmette-Guérin (BCG) ha sido reportada en relación a inmunodeficiencias primarias, secundarias y en el síndrome clínico denominado susceptibilidad mendeliana a enfermedades micobacterianas. La investigación de este síndrome ha llevado a la identificación de defectos en el eje interleuquina (IL)- 12/ interferón gamma (IL-12/IFN-γ), habiéndose identificado hasta hoy mutaciones en siete genes autosómicos y dos ligados al cromosoma X. En estos pacientes, las infecciones localizadas o generalizadas por BCG vacunal son comunes. Reportamos una serie clínica constituida por dos lactantes con adenomegalia axilar izquierda recurrente secundaria a vacunación BCG al nacer; uno de ellos integrante de una familia con dos casos reportados previamente y un caso aislado, diagnosticados consecutivamente en Puerto Montt, Chile, con el objetivo de notificar los primeros casos chilenos de diseminación BCG en niños sin inmunodeficiencia previa conocida, en los que se logró identificar la deficiencia inmune subyacente pese a no disponer en el país del estudio específico del eje (IL-12/IFN-γ). La sospecha diagnóstica y colaboración internacional permitieron identificar en dos de los tres casos familiares y en el caso aislado, la deficiencia del receptor β1 de IL 12 (IL12Rβ1).
Assuntos
Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Adulto Jovem , Vacina BCG/efeitos adversos , Predisposição Genética para Doença , Infecções por Mycobacterium não Tuberculosas/genética , /deficiência , /genética , Idade de Início , Mutação , Infecções por Mycobacterium não Tuberculosas/diagnóstico , LinhagemRESUMO
Association of HLA-DR2 genes/gene products has been shown with pulmonary tuberculosis (PTB) patients in India. In the present study, the influence of HLA-DR2 and non-DR2 genes/gene products on immunity to tuberculosis has been studied. Plasma samples of -DR2 positive patients (active and inactive TB) showed a higher antibody titre to Mycobacterium tuberculosis culture filtrate antigens than non-DR2 (-DR2 negative) patients. Immunoblot analysis revealed a trend towards an increased percentage of DR2 positive patients recognizing 38, 32/34 and 30/31 kDa antigens of M. tuberculosis than DR2 negative patients. A low spontaneous lymphoproliferative response (without antigen stimulation) was seen in HLA-DR2 positive active TB patients than HLA-DR2 negative patients. However, the antigen stimulated lymphocyte response was higher in the -DR2 positive patients (active and inactive TB) when compared to non-DR2 patients. Further, an inversional correlation between antibody titre and spontaneous as well as antigen induced lymphocyte response (measured by 3H thymidine uptake and expressed as counts per minute) was seen in HLA-DR2 positive active PTB patients than non-DR2 patients. The present study suggests that HLA-DR2 genes/gene products may be associated with a regulatory role in the mechanism of disease susceptibility to tuberculosis. The genes while augmenting the humoral immune response, they suppress the spontaneous and antigen induced lymphocyte response in -DR2 positive patients with active disease.