RESUMO
INTRODUCTION: Association between inherited deficiencies of the complement components and immune complex disease indicates the importance of the complement system in the handling of circulating immune complexes. High levels of circulating immune complexes are seen in pulmonary tuberculosis. This study is, therefore, aimed to look at the concentration of circulating immune complexes, the status of complement-mediated immune complex handling, and the extent of complement activation in untreated pulmonary tuberculosis compared to treated pulmonary tuberculosis patients and healthy controls. RESULTS: High immune complex levels, decreased complement-mediated solubilization, and increased activation of the complement system were observed in untreated tuberculosis patients. CONCLUSIONS: The results obtained from the present study suggest that complement mediated solubilization is less in patients with tuberculosis, and this defective solubilization is likely to take part in a vicious cycle involving immune complex deposition and complement activation and, thus, may lead to disease progression depending on the nature of the defect.
Assuntos
Complexo Antígeno-Anticorpo/biossíntese , Complemento C3/metabolismo , Complemento C4/metabolismo , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Complexo Antígeno-Anticorpo/sangue , Complexo Antígeno-Anticorpo/genética , Biomarcadores/sangue , Ativação do Complemento/genética , Complemento C3/genética , Complemento C3/imunologia , Complemento C4/genética , Complemento C4/imunologia , Citotoxicidade Imunológica , Feminino , Humanos , Doenças do Complexo Imune/congênito , Masculino , Pessoa de Meia-Idade , Monitorização Imunológica , Mycobacterium tuberculosis/patogenicidade , Prognóstico , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/fisiopatologia , VirulênciaRESUMO
Complement receptor 1 expressed on erythrocytes is involved in the transport of circulating immune complexes from the circulation to the mononuclear phagocyte system for safe disposal. The prevalence of complement receptor 1 genotypes and the association between circulating immune complexes and expression of complement receptor 1 on erythrocytes in pulmonary tuberculosis are not fully understood. Observations from this study showed increased occurrence of HH genotype in patients with pulmonary tuberculosis. Patients with tuberculosis had decreased erythrocyte complement receptor 1 and increased immune complex levels compared to healthy controls which also correlated with increasing severity of the disease. In addition, the expression of complement receptor 1 on erythrocytes correlated inversely with the levels of circulating immune complexes. This study suggests that the presence of HH genotype is high in pulmonary tuberculosis patients and the reduced complement receptor 1 in patients may be an acquired phenomenon related to disease pathogenesis.
Assuntos
Eritrócitos/metabolismo , Receptores de Complemento 3b/biossíntese , Receptores de Complemento 3b/genética , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/metabolismo , Adulto , Complexo Antígeno-Anticorpo/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo Genético , Tuberculose Pulmonar/sangueRESUMO
The complement system is an integral part of the host immune system and plays an immunoregulatory role at the interface of innate and acquired immune responses. Limited data are available on the influence of variations in complement genes in infectious diseases such as pulmonary tuberculosis (PTB). The aim of this study was to investigate the role of genetic variations in complement system components C2, C4, BF, and C3 in PTB (n = 125) compared with healthy controls (n = 125) in the Indian population. The study showed, for the first time, an increased occurrence of null alleles at the C4A, i.e., C4AQ0; an increased frequency of BF*FA and C3*F in patients with PTB compared with healthy individuals, and contributed a risk with odds ratios of 18.16 (95% confidence interval [CI] = 3.0-108.6, p = 0.0004), 2.9 (95% CI = 1.9-4.37, p(c) = 3.15E-06), and 2.26 (95% CI = 1.5-3.3, p(c) = 6.7E-05), respectively. A combinatorial analysis of complement gene variants as risk determinants and their phenotypic effects in various populations may provide unique insights into the genetic basis of susceptibility to PTB.