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Selective correlation of interferon‐γ, tumour necrosis factor‐α and granulocyte–macrophage colony‐stimulating factor with immunoglobulin G1 and immunoglobulin G3 subclass antibody in leprosy
Author(s) -
Rabia Hussain,
Arnawaz Kifayet,
Maqboola Dojki,
Hazel M. Dockrell
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00876.x
Subject(s) - immunology , antibody , cytokine , biology , tumor necrosis factor alpha , antigen , immunoglobulin g , interferon gamma , immune system , t cell , granulocyte macrophage colony stimulating factor , macrophage , biochemistry , in vitro
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‐γ (IFN‐γ), interleukin‐2 (IL‐2), IL‐5, IL‐10, IL‐6, tumour necrosis factor‐α (TNF‐α) 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‐γ 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‐γ may play a role in down‐regulating antigen‐specific IgG1 and IgG3 antibodies. Among the macrophage cytokines, TNF‐α and GM‐CSF which have not been shown to play a role in B‐cell activation were positively associated with IgG1 (TNF‐α, P =0·0005; GM‐CSF, P =0·001) and IgG3 (TNF‐α, 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‐α, 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.