02844nas a2200313   4500000000100000008004100001260001300042653002600055653002000081653001400101653005300115653001100168653003500179653002100214653002100235653001200256653001600268653001800284653003200302100001400334700001400348700001200362700001700374245020400391300001100595490000700606520190300613022001402516       1999                            d  c1999 Oct10aAntibodies, Bacterial10aCells, Cultured10aCytokines10aGranulocyte-Macrophage Colony-Stimulating Factor10aHumans10aImmunoglobulin Class Switching10aImmunoglobulin G10aInterferon-gamma10aleprosy10aMacrophages10aT-Lymphocytes10aTumor Necrosis Factor-alpha1 aHussain R1 aKifayet A1 aDojki M1 aDockrell H M00aSelective correlation of interferon-gamma, tumour necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor with immunoglobulin G1 and immunoglobulin G3 subclass antibody in leprosy.  a238-430 v983 a<p>Dysregulation of both B- and T-cell responses is observed in leprosy. Immunoglobulin G1 (IgG1) and IgG3 antibody subclasses are selectively elevated towards 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 examined the relationship between circulating Mycobacterium leprae-specific antibodies and secreted cytokines [interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-5, IL-10, IL-6, tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF)] in leprosy patients (19 lepromatous patients; 25 tuberculoid patients) and their exposed household contacts (HC=14) in response to M. leprae antigens. Paired comparison revealed a highly significant negative correlation between IFN-gamma and IgG (P=0.016), IgG1 (P<0.001) and IgG3 (P=0. 007) antibodies. No significant 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 macrophage cytokines, TNF-alpha and GM-CSF which have not been shown to play a role 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 may influence cytokine expression of TNF-alpha, a key modulator of disease pathogenesis in mycobacterial diseases. We are currently investigating the role of Fc receptors on activated macrophages, in expression of pro-inflammatory cytokines in mycobacterial diseases.</p>  a0019-2805