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

Circulating antibodies to the 60-kD heat shock protein (hsp) family in patients with Helicobacter pylori infection

Whilst the mechanism by which Helicobacter pylori causes different gastroduodenal diseases is uncertain, strains producing the cytotoxin-associated protein (CagA) have greater pathogenicity. Hsps are immunogenic molecules induced by inflammatory mediators. The aim of this study was to assess pathogenicity of hsp antibodies in H. pylori-infected patients. ELISA techniques were used to assay sera of H. pylori-positive patients with gastritis, gastric atrophy, duodenal or gastric ulcer, and H. pylori-negative controls, for antibodies to CagA and to human, mycobacterial, and in 20 sera, H. pylori (hspB) 60-kD hsp. IgA antibodies to mycobacterial hsp60 in atrophy patients were elevated compared with patients with gastritis (P < 0.05) and with H. pylori-negative controls (P < 0.0005). IgA antibodies to human hsp60 in gastric atrophy patients were elevated compared with H. pylori-negative controls (P < 0.05). Patients with atrophy (P < 0.0005) and gastritis (P < 0.05) who were CagA-positive had raised titres of anti-mycobacterial hsp60 IgA antibodies compared with controls. IgA antibody levels to hspB were positively correlated with those to mycobacterial hsp60 (mhsp60) (P < 0.05) and human hsp60 (hhsp60) (P < 0.005). IgA antibodies to hsp60 are associated with gastroduodenal disease, particularly gastric atrophy, in H. pylori-infected patients. Increased humoral responses to hsp60 could either contribute to gastric atrophy or result from greater gastric mucosal damage induced by CagA-positive strains of H. pylori