Selective correlation of interferon-gamma, tumour necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor with immunoglobulin G1 and immunoglobulin G3 subclass antibody in leprosy

Dysregulation of both B- and T-cell responses is observed in leprosy. Immun oglobulin G1 (IgG1) and IgG3 antibody subclasses are selectively elevated t owards the lepromatous or disseminated form of the disease accompanied by a depression of T-cell responses. T-cell and macrophage cytokines influence antibody class switching, differentiation and proliferation of B cells. To understand the dynamic nature of the immune response in leprosy, we examine d the relationship between circulating Mycobacterium Leprae-specific antibo dies and secreted cytokines [interferon-gamma (IFN-gamma), interleukin-2 (I L-2), IL-5, IL-10, IL-6, tumour necrosis factor-alpha (TNF-alpha) and granu locyte-macrophage colony-stimulating factor (GM-CSF)] in leprosy patients ( 19 lepromatous patients; 25 tuberculoid patients) and their exposed househo ld contacts (HC = 14) in response to M. leprae antigens. Paired comparison revealed a highly significant negative correlation between IFN-gamma and Ig G (P = 0 . 016), IgG1 (P < 0 . 001) and IgG3 (P = 0 . 007) antibodies. No s ignificant relationship was observed with other T-cell cytokines (IL-2, IL- 5 and IL-10). These results strongly suggest that IFN-gamma may play a role in down-regulating antigen-specific IgG1 and IgG3 antibodies. Among the ma crophage cytokines, TNF-a and GM-CSF which have not been shown to play a ro le in B-cell activation were positively associated with IgG1 (TNF-alpha, P = 0 . 0005; GM-CSF, P = 0 . 001) and IgG3 (TNF-alpha, P = 0 . 001; GM-CSF, P = 0 . 021) antibodies. Since macrophages have high-affinity Fc receptors for IgG1 and IgG3, it is possible that antigen uptake via these receptors m ay influence cytokine expression of TNF-alpha, a key modulator of disease p athogenesis in mycobacterial diseases. We are currently investigating the r ole of Fc receptors on activated macrophages, in expression of pro-inflamma tory cytokines in mycobacterial diseases.