Cellular and humoral immune responses to mycobacterial heat shock protein-65 and its human homologue in Takayasu's arteritis.
Expression of heat shock protein (HSP)-65 as well as infiltration of T-cells in arterial lesions and raised levels of circulating antibodies against mycobacterial HSP65 (mHSP65) led us to the concept that mHSP65 or its human homologue (hHSP60) might be involved in the etiopathogenesis of Takayasu's arteritis (TA). Therefore, we investigated mHSP65 and hHSP60 reactive peripheral blood T-cell subsets by BrdU incorporation assay and flow cytometry as well as investigating the different isotypes of anti-mHSP65 and hHSP60 antibodies by ELISA. Eighty-four percent (22/26) of the TA patients were observed to show T-cell proliferation to mHSP65 and hHSP60 whereas only 16% (3/18) healthy controls showed such proliferation (P <0.001). Both HSPs induced proliferation of exclusively CD4+ T-cells and not CD8+ T-cells. We also observed a significantly higher prevalence of only the IgG isotype reactive to mHSP65 and hHSP60 in TA as compared to HC (mHSP65: 92% TA versus 11% HC, P <0.0001 and hHSP60: 84% versus 22%, P <0.001). Our data show a significant correlation between mHSP65 and hHSP60 reactive T-cells (CD3+: r=0.901; CD4+: r=0.968) as well as anti-mHSP65 and anti-hHSP60 IgG antibodies (r=0.814) suggesting an infection induced autoimmunity in TA, possibly induced by molecular mimicry between mHSP65 and hHSP60 or other tissue specific antigens.
Kumar Chauhan
S
S
Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Kumar Tripathy
N
N
Sinha
N
N
Singh
M
M
Nityanand
S
S
D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000276:immunology*; D018833:Chaperonins / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013625:Takayasu Arteritis / Q000276:immunology*
D000906:Antibodies; D001426:Bacterial Proteins; D018834:Chaperonin 60; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins