Does antibody to mycobacterial antigens, including lipoarabinomannan, limit dissemination in childhood tuberculosis?

Abstract

Serum immunoglobulin (Ig) G responses to a variety of mycobacterial antigens were measured in children from the UK, in children with tuberculosis from Hyderabad, India and Dhaka, Bangladesh, classified according to whether the disease was disseminated or localized, and in non-tuberculous controls. Anti-lipoarabinomannan (LAM) IgG responses in UK children showed a marked trough between 6 months and 3 years coincident with the reported peak incidence of disseminated tuberculosis. Geometric mean IgG responses to sonicates of slow-growing mycobacteria (rich in LAM) in 36 children with disseminated tuberculosis were markedly lower than in 99 children with localized tuberculous lesions (for Mycobacterium scrofulaceum P < 0.01, for M. tuberculosis P < 0.01, and for M. vaccae P < 0.01). Responses to purified LAM were also lower in the disseminated tuberculosis group (P < 0.05) but there was no difference between the groups in their response to mycobacterial 65 kDa protein. Multiple regression analysis showed that the reduced response to sonicated mycobacterial antigens and to LAM in children with disseminated disease was independent of age, nutritional status, skin test reactivity, duration of previous symptoms, and city of origin. There was no evidence for sequestration of antibody to immune complexes. These findings are compatible with the hypothesis that children with low levels of antibody to sonicated mycobacterial antigen and to LAM, or those who cannot mount an antibody response, are predisposed to dissemination. A role for antibody in preventing disseminated forms of tuberculosis in childhood has implications for the development of improved vaccines and for the optimum timing of vaccination with bacille Calmette-Guérin.

Increase of tuberculous infection in the organs of B cell-deficient mice

“…Third, association between antibody levels of certain specificity and clinical features [7,8] is also indicative of a possible role of antibodies in the development of tuberculosis in man. Antibodies could neutralize soluble mycobacterial components like LAM, which has been shown to suppress T cell responses in vitro [26].…”

“…A soluble extract from M. tuberculosis H37Rv (MTSE) was prepared as described earlier [8]. The recombinant 38-kD protein [13] was obtained through the WHO protein bank (Braunschweig, Germany); concanavalin A (Con A) from Sigma (Poole, UK).…”

Therapeutic Efficacy of High-Dose Intravenous Immunoglobulin inMycobacterium tuberculosisInfection in Mice

“…Several studies have shown a correlation between protection and the presence of serum antibodies to mycobacterial carbohydrates; there have been suggestions that low levels of anti-LAM IgG in serum increase the risk of dissemination in childhood TB (8) and that serum antibodies to LAM are involved in classical complement activation by mycobacteria (16). A monoclonal antibody specific for LAM has been shown to prolong survival in M. tuberculosisinfected mice; this antibody showed neither bactericidal nor inhibitory activity against infection or bacterial replication; however, it greatly altered the nature of the lung granulomas, suggesting it acted via enhancement of the cell-mediated re- sponse (32).…”

Towards a New Challenge in TB Control: Development of Antibody-Based Protection

“…Children with low serum IgG against sonicated mycobacterial antigens and LAM, or those who cannot mount antibody responses to these antigens, were predisposed to dissemination of the bacteria [18]. In another report, Kamble and colleagues reported that M. leprae reactive salivary IgA antibodies could be quite important in a mucosal protective immunity [19].…”