ABSTRACT
Host genetic susceptibility to adult pulmonary Mycobacterium avium complex disease remains unknown. To identify genetic loci for the disease, we prepared 3 sets of pooled DNA samples from 300 patients and 300 sex-matched control subjects and genotyped 19,651 microsatellite markers in a case-control manner. D6S0009i-located in the MICA (major histocompatibility complex class I chain-related A) gene, which encodes a ligand of the NKG2D receptor-had the lowest P value in pooled and individual DNA typing. The A6 allele of the microsatellite was significantly associated with female patients (P <. 001), whereas the classical HLA-B and HLA-DRB1 alleles did not show significant association. Functional analysis of allelic expression imbalance revealed that A6-derived messenger RNA was more highly expressed than non-A6-derived messenger RNA in human bronchial epithelial cells. MICA was expressed in bronchiolar epithelium, alveolar macrophages, and granulomatous lesions. These findings suggest that MICA might be one of the immune molecules affecting the pathogenesis of the disease.
Subject(s)
Genetic Predisposition to Disease , Histocompatibility Antigens Class I/genetics , Lung Diseases/microbiology , Mycobacterium avium-intracellulare Infection/genetics , Female , Gene Frequency , Genetic Carrier Screening , Genetic Markers , Genotype , HLA Antigens/genetics , Humans , Lung Diseases/pathology , Male , Microsatellite Repeats/genetics , Mycobacterium avium-intracellulare Infection/pathology , Polymorphism, Genetic , Sex CharacteristicsABSTRACT
In Japan and other countries where tuberculosis is not so common, people who were once infected with tuberculosis are thought to rarely suffer from the disease again due to exogenous reinfection. We experienced a mass outbreak of tuberculosis with 27 patients (including the source of infection) at a nursing home for the elderly. Epidemiological investigation suggested that the source of infection was an 82-year-old woman resident. For about 2 years before this outbreak, she had complained of a productive cough. At the time of the diagnosis of tuberculosis, chest radiography revealed a cavitary lesion and a smear of her sputum revealed organisms rated as Gaffky No. 8. Sputum culture was also positive (++++). Of the 27 patients, 19 (including the source) underwent restriction fragment length polymorphism (RFLP) analysis of isolates from the sputum. Eighteen patients showed an identical RFLP pattern, indicating that the infection had arisen from one source. Out of all patients, the source case of infection, 9 others with the same RFLP pattern, and other 3 who did not undergo RFLP analysis were admitted to our hospital. In 12 patients (3 men and 9 women excluding the source case) aged 80.6 years (range: 67-89 years), chest radiography disclosed tuberculous lesions, and smears, the polymerase chain reaction, and culture of sputum demonstrated Mycobacterium tuberculosis. As the prevalence of tuberculosis infection in Japanese aged 80 years at the time of the mass outbreak (1995) was presumed to be about 80%, the disease seemed to be caused by exogenous reinfection in most of these patients. All of the patients had senile dementia and other complications, and they were bedridden and undernourished. Anemia, hypoalbuminemia and lymphocytopenia were also observed in most of the cases. Malnutrition due to these complications appeared to be a possible risk factor of tuberculosis caused by exogenous reinfection.
