ABSTRACT
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.
Subject(s)
Complement C2/genetics , Complement C3/genetics , Complement C4/genetics , Complement Factor B/genetics , Major Histocompatibility Complex/genetics , Tuberculosis, Pulmonary/genetics , Tuberculosis, Pulmonary/immunology , Adult , Alleles , Complement C2/immunology , Complement C3/immunology , Complement C4/immunology , Complement Factor B/immunology , DNA Fingerprinting , Female , Gene Frequency/immunology , Genetic Predisposition to Disease/ethnology , Genetic Variation/immunology , Humans , India , Linkage Disequilibrium/genetics , Linkage Disequilibrium/immunology , Major Histocompatibility Complex/immunology , Male , Phenotype , Polymerase Chain Reaction , Risk Factors , Tuberculosis, Pulmonary/epidemiologyABSTRACT
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.
Subject(s)
Antigen-Antibody Complex/biosynthesis , Complement C3/metabolism , Complement C4/metabolism , Mycobacterium tuberculosis/immunology , Tuberculosis, Pulmonary/immunology , Adult , Antigen-Antibody Complex/blood , Antigen-Antibody Complex/genetics , Biomarkers/blood , Complement Activation/genetics , Complement C3/genetics , Complement C3/immunology , Complement C4/genetics , Complement C4/immunology , Cytotoxicity, Immunologic , Female , Humans , Immune Complex Diseases/congenital , Male , Middle Aged , Monitoring, Immunologic , Mycobacterium tuberculosis/pathogenicity , Prognosis , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/genetics , Tuberculosis, Pulmonary/physiopathology , VirulenceABSTRACT
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.
