ABSTRACT
Key measures to halt the spread of tuberculosis (TB) include early diagnosis, effective treatment, and monitoring disease management. We sought to evaluate the use of serum immunoglobulin levels against antigens present in cell envelope of Mycobacterium tuberculosis to monitor TB treatment response in children and adolescents with pulmonary (PTB) or extrapulmonary TB (EPTB). Blood samples were collected prior to and one, two, and six months following treatment initiation. Serum immunoglobulin levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein were measured by ELISA. Serum from 53 TB patients and 12 healthy participants were analyzed. After six months of successful treatment, there was a significant decrease (p < 0.0001) in IgM levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein and IgG levels against Mce1A protein when compared to baseline immunoglobulin levels. There was no significant variation in antibody levels during follow-up between participants with PTB and EPTB, confirmed and unconfirmed TB diagnosis, and HIV infection status. Antibody levels in control participants without TB did not decrease during follow-up. These results suggest that immunoglobulin responses to mycobacterial cell wall products may be a useful tool to monitor treatment response in children and adolescents with PTB or EPTB.
Subject(s)
Antitubercular Agents/therapeutic use , Drug Monitoring , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G/blood , Immunoglobulin M/blood , Mycobacterium tuberculosis/drug effects , Tuberculosis, Pulmonary/drug therapy , Adolescent , Age Factors , Bacterial Proteins/immunology , Biomarkers/blood , Cardiolipins/immunology , Case-Control Studies , Child , Child, Preschool , Female , Humans , Infant , Male , Mycobacterium tuberculosis/immunology , Mycolic Acids/immunology , Predictive Value of Tests , Prospective Studies , Sulfoglycosphingolipids/immunology , Time Factors , Treatment Outcome , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/microbiologySubject(s)
Antibodies, Bacterial/blood , Bacterial Proteins/immunology , Immunoglobulin G/blood , Latent Tuberculosis/diagnosis , Mycobacterium tuberculosis/immunology , Serologic Tests , Tuberculosis, Pulmonary/diagnosis , Adolescent , Age Factors , Biomarkers/blood , Brazil , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , Immunoglobulin M/blood , Infant , Infant, Newborn , Latent Tuberculosis/blood , Latent Tuberculosis/immunology , Latent Tuberculosis/microbiology , Male , Predictive Value of Tests , Prospective Studies , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/microbiologyABSTRACT
Chagas disease (CD) is caused by Trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (MBL), a soluble pattern-recognition molecule that activates the lectin pathway of complement. MBL levels and protein activity are affected by polymorphisms in the MBL2 gene. We sequenced the MBL2 promoter and exon 1 in 196 chronic CD patients and 202 controls. The MBL2*C allele, which causes MBL deficiency, was associated with protection against CD (P = 0.007, OR = 0.32). Compared with controls, genotypes with this allele were completely absent in patients with the cardiac form of the disease (P = 0.003). Furthermore, cardiac patients with genotypes causing MBL deficiency presented less heart damage (P = 0.003, OR = 0.23), compared with cardiac patients having the XA haplotype causing low MBL levels, but fully capable of activating complement (P = 0.005, OR = 7.07). Among the patients, those with alleles causing MBL deficiency presented lower levels of cytokines and chemokines possibly implicated in symptom development (IL9, p = 0.013; PDGFB, p = 0.036 and RANTES, p = 0.031). These findings suggest a protective effect of genetically determined MBL deficiency against the development and progression of chronic CD cardiomyopathy.