Levels of complement C3 and C4 components in Amerindians living in an area with high prevalence of tuberculosis

Abstract

The levels of complement C3 and C4 components were determined in non-indigenous (creoles) and indigenous (Warao) populations, the latter with an extremely high tuberculosis (TB) rate. Serum samples from 209 adults were studied and classified in 4 groups taking into account tuberculin skin tests (TST): (1) the group of Warao patients (58 positive for the TST, WP TST+ and 9 negative for the TST, WP TST-), (2) the group of creole patients (34 positive for the TST, CP TST+ and 9 negative for the TST, CP TST-), (3) the group of healthy Warao controls (38 positive and 14 negative for TST, WC TST+ and WC TST-, respectively), (4) the creole controls (26 positive and 21 negative for the TST, CC TST+ and CC TST-, respectively). With respect to the results concerning the measurement of both complement C3 and C4 components with the exception of the WC TST-and the CC groups, the WP TST+ and WP TST-as well as WC TST+ groups showed a significant frequency of individuals with decreased levels of complement C3 component (20.6, 33.3, and 26.3%, respectively) and also C4 component (12.0, 11.1, and 13.3%, respectively) in comparison to both creole patients (CP TST+, 0% and CP TST+, 0%) for C3 and C4, respectively . The study of these parameters carried out in 15 Warao subjects with active infection, before and after anti-TB chemotherapy, statistically confirmed that the effective chemotherapy did not restore normal levels of the complement C3 and C4 components among Warao patients. Aditional tests for hepatitis B or hepatitis C infection, and the profile of the hepatic proteins were not associated to the deficiency in production of the complement components. In conclusion, the results show that within the Warao population, a high percentage of subjects exhibit decreased levels of both complement C3 and C4 components independent of latent or active infection and the status of TST.Key words: tuberculosis -body mass index -indigenous Warao -creole -complement C3 and C4 components There were an estimated 8.4 million new tuberculosis cases in 1999, up from 8 million in 1997; the rise is due largely to a 20% increase in incidence in African countries most affected by the epidemic of HIV/AIDS. If present trends continue, 10.2 million new cases are expected in 2005, and Africa will have more cases than any other region of the world (WHO 2003). Evidence shows that complement plays a protective role in the host response to infection by different intracellular pathogens such as Mycobacterium tuberculosis. It has been reported that the outcome of the infection is associated with an enhancement of elements of the innate immune system, which include small peptides, such as defensins, that have the capacity to interact with and destroy organisms (Lehrer et al. 1993); receptor systems on phagocytes, such as Toll-like receptor and CD14, which facilitate the phagocytic and signaling processes by recognition of lipo- polyssaccharide and sugars on the surface of organims (Michael 2000). The complement proteins are of interest because they seem to b...

Screening and identification of five serum proteins as novel potential biomarkers for cured pulmonary tuberculosis

“…The complement system has been seriously studied in TB studies 23 33 34 35 . As a part of the complement system, C3 is potentially related to TB pathogenesis 34 and anti-TB treatment 35 . Our study revealed a C3 level reduction in cured TB patients ( P = 0.035).…”

Genetic polymorphism and immune response to tuberculosis in indigenous populations: a brief review

“…Most of the studies were based on small sample sizes. The studies that assessed the largest population samples were conducted on the Yanomami in 1997, 18 the Xavante in 2010, 22 and the Warao in 2008 23 , 24 , 25 , 26 , 27 ( Table 1 ). Despite the small sample sizes, both adults and children were included in our analysis.…”

“…Only Giampietro et al 27 evaluated the proliferative capacity of peripheral blood mononuclear cells (PBMC) after treatment with antigen and investigated the resulting cytokine levels ( Table 1 ). Most studies analyzed the humoral immune response to TB 18 , 23 , 24 , 25 , 26 , 27 by measuring the concentration of immunoglobulins (IgG, IgG1, IgG2, IgG3, IgG4, IgM, IgA, saliva IgA and IgE) and complement fractions (C3 and C4). A large proportion of the studies used the TST as an indirect indicator of the cellular immune response, and two also tested the skin response to Candida as a control of the individual's ability to initiate a cellular response ( Table 1 ).…”

In vitro levels of cytokines in response to purified protein derivative (PPD) antigen in a population with high prevalence of pulmonary tuberculosis

“…In addition they do not have access to health care compared with the Creole people from the urban areas. Warao individuals also have recurrent or overwhelming parasite infections [11,30]. A significant association between intestinal helminthic infections and mycobacterial diseases, such as pulmonary TB and multibacillary leprosy, has been demonstrated by several authors [31,32].…”