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Cachexia is one of the prominent features of advanced tuberculosis (TB) seen in association with increased expression of the monokine TNF-α. Several mycobacterial proteins, including PPD, stimulate TNF-α secretion from monocytes. Host factors that may play a role in cytokine expression from monocytes remain largely unknown. One such factor is the opsonizing antibodies. Monocytes have high-affinity receptors (FcγI and FcγIII) for IgG1 and IgG3 antibodies that mediate antigen uptake. We have reported selective up-regulation of IgG1 (which bind to Fcγ receptors) in advanced TB and have recently shown the ability of PPD-specific IgG1 antibodies to augment TNF-α expression in PPD-stimulated monocytes. These observations have now been extended to other cytokines with semipurified fractions from secreted antigens of Mycobacterium tuberculosis (containing 30 kD and 58 kD) that were devoid of lipids, glycolipids and carbohydrates. In the presence of heat-inactivated TB plasma containing known amounts of antigen-specific IgG1 antibodies, these fractions induced significantly increased TNF-α, IL-6 and IL-10 secretion. Absorption of IgG1 with Protein ‘A’ removed the augmenting activity for TNF-α and IL-6 secretion from the TB plasma samples. In the case of IL-10, removal of IgG1 resulted in increased rather than decreased IL-10 secretion. These results suggest a possible pathogenic role for antibodies in TB by enhancing proinflammatory and blocking down-regulatory cytokines such as IL-10 cytokines during the chronic phase of TB. [ABSTRACT FROM AUTHOR]

IgG subclass responses to Mycobacterium leprae 18000MW recombinant antigen (18K) were determined in sera from untreated leprosy patients using an ELISA-based assay with specific monoclonal antibodies. Antibodies to M. leprae 18K were restricted to IgG1 and IgG3 antibodies with higher seropositivity in lepromatous patients (25.5% for IgG1 and 12.8% for IgG3) compared to patients with tuberculoid disease (11.5% for IgG1 and 5% for IgG3). No significant antibody response was detectable in IgG2 and IgG4 in patients with either lepromatous or tuberculoid leprosy. The selective production of antibodies in IgG1 and IgG3 subclasses could not be related to polyclonal activation in these subclasses as all IgG subclasses showed similar elevated levels at the polyclonal level. The major difference noted between lepromatous and tuberculoid leprosy patients with the IgG subclass antibody response was a strong linear correlation between IgG1 and IgG3 responses to M. leprae 18K in lepromatous patients (r = 0.703, P < 0.001) but not in tuberculoid leprosy patients (r = 0.007, P > 0.10) which may be related to immunoglobulin class switching of IgG3 to IgG1 rather than selective shifts in T-helper subsets. Our results therefore, do not support the hypothesis that activation of Th2 cells occurs in lepromatous leprosy; this issue needs further examination. [ABSTRACT FROM AUTHOR]

Erythema nodosum leprosum (ENL) is a serious complication of lepromatous (L) disease in leprosy. We have previously shown that of the four IgG subclasses, IgGl and IgG3 Mycobacterium leprae-specific antibodies are significantly lower in leprosy patients during ENL reaction compared with untreated L patients. To see if this decrease results from a down-regulation of antibody synthesis during ENL, the frequency of antibody-secreting B cells (ABSC) in the blood compartment was determined by ELISPOT and related to serum immunoglobulin concentrations (μg/ABSC). Control groups consisted of 16 patients with stable L disease and 32 healthy endemic controls (EC). Paired samples were analysed during acute ENLS (n=13) and after the reaction had subsided to identify changes associated with ENL. Polyclonal (PC) IgGl was elevated in L patients compared with EC (325μg versus 180 μg). Interestingly, patients during acute ENL showed concentrations higher than L patients (419μg), which decreased after the reaction had subsided (260μg), indicating the transient nature of the antibody response. IgG2 antibodies showed the reverse trend and were lower during ENL and increased after the reaction had subsided. The mean concentrations for PC IgG3 and IgG4 antibodies were similar during ENL and after the reaction had subsided. Thus, decrease in M. leprae-specific IgGl and IgG3 antibodies is not related to down-regulation of B cell responses. Identification of factors which regulate PC IgGl antibody synthesis may provide additional insights into determinants of ENL reactions. [ABSTRACT FROM AUTHOR]