DPhil, FRCP; for the Heart Outcomes Prevention Evaluation (HOPE) Study InvestigatorsBackground-Several recent studies have indicated an association between key inflammatory mediators and atherosclerotic diseases. We evaluated whether high levels of antibodies against heat shock proteins and cholesterol (ACHA) predicted cardiovascular (CV) events. Methods and Results-We used blood samples from the Heart Outcomes Prevention Evaluation (HOPE) study to conduct a nested case-control study of 386 cases with CV events and 386 age-and sex-matched HOPE study controls without events. We explored the relationship between anti-hsp antibodies, ACHA, and subsequent outcomes (incident myocardial infarction, stroke, or CV death) during a mean follow-up of 4.5 years using conditional logistic regression. High levels of anti-hsp65 antibodies (Ն90th percentile) predicted CV events (OR, 2.1; 95% CI, 1.2 to 3.9, Pϭ0.01). Anti-hsp60 antibodies did not predict any event type, whereas incident stroke developed significantly less frequently in patients with high ACHA levels. Anti-hsp antibodies and ACHA did not correlate with inflammatory (fibrinogen, C-reactive protein, interleukin-6, intracellular adhesion molecule-1) or infectious markers (C pneumoniae or cytomegalovirus antibodies). Anti-hsp65 antibodies (Ն90th percentile) and fibrinogen (highest tertile) had a strong joint effect: patients with high concentrations of both had more CV events (OR, 5.5; 95% CI, 1.8 to 17.5, Pϭ0.004) than patients with low levels of both. A similar joint effect (OR, 2.7; 95% CI, 1.3 to 5.7, Pϭ0.01) was found for high levels of anti-hsp65 and presence of cytomegalovirus antibodies. Conclusions-Serum antibodies to hsp65 were associated with subsequent CV events in this study of high-risk patients, independent of conventional cardiovascular risk factors and other inflammatory markers. (Circulation. 2002;106:2775-2780.)

These findings indicate that in autoimmune diseases the infection with the H. pylori bacterium is associated with increased concentration of antimycobacterial hsp65.

Heat shock proteins (hsps) play complex role in the function of the immune system, they can activate both humoral and cellular immune response, as well the complement system. Although autoimmunity to hsp70 was implicated in certain autoimmune diseases and other conditions, the exact role of anti-hsp70 antibodies is not known. It was demonstrated by our previous work and other's findings that antibodies against the 60 kDa hsps are strongly associated with coronary atherosclerosis and carotis disease. It is also known that there is increased hsp70 expression at different sites of atherosclerosis. Therefore our aim was to study whether level of anti-hsp70 antibodies correlate with the presence of severe coronary artery disease (CAD). We measured and compared anti-hsp70 IgG antibody levels in CAD patients (n = 99) and healthy subjects (n = 99) with ELISA. The frequency of these antibodies was high in both groups and there was no significant difference in the median level of anti-hsp70 antibodies between patients with severe CAD and controls (653 (400-1141) vs. 630 (326-1152) AU/mL, P = 0.337). Adjustment for age, sex, BMI and lipid parameters did not change this result. Furthermore we did not find a correlation between anti-hsp70 antibody levels and certain risk factors of CAD (age, lipid parameters, body mass index, C-reactive protein, gender, smoking, diabetes and anti-hsp60 antibodies). By contrast, in accordance with our previous findings, anti-hsp60 and anti-hsp65 antibody levels were significantly higher in CAD patients, compared to this control group (p < 0.0001 for both variables). We did not find any correlation between the levels of anti-hsp70 and anti-hsp60 or anti-hsp65 antibodies either in the patients or the controls. The exact role of hsp70 in atherosclerosis is controversial, but we suggest that humoral immunity against human hsp70 does not contribute to coronary atherosclerosis in contrast to antibodies against 60kDa hsps.

OCT enabled a noninvasive, high-resolution method of imaging, evaluating, and classifying LIPCOFs. These new classifications correlated well with the slit lamp grade and the DEQ scores, promising a new, more objective evaluation of dry eye.

FD-OCT could be a quick, non-invasive, quantitative method for the imaging of LIPCOF in contact lens patients. When grading LIPCOF, the mechanical forces of the lens and the tear meniscus changes caused by the lens should be taken into account as these factors influence results. Follow-up of the patients using the same methods is suggested with or without contact lenses.

These findings indicate that high levels of CA autoantibodies against hsp60 can be considered to be a novel family risk factor of CHD, independent of HDL- and LDL-cholesterol levels.

The aim of this study was to explore complement activation in the nasal lavage following a nasal ragweed-allergen challenge. The study was carried out with 15 adolescents who were allergic to ragweed and with six non-allergic healthy volunteers. Following the baseline measurement after the symptoms were registered, subjects were given increasing doses of ragweed allergen. Lavage fluid was collected and tested for a complement-activation product (C3bBbP). The allergic patients responded to allergen provocation with an increase in C3bBbP formation compared to the initial lavage (p = 0.001). The C3bBbP level remained low in the lavage fluids of the non-allergic controls. We found a strong correlation between the threshold dose that induced symptoms and the dose where the maximum complement activation was detected (r = 0.78, p = 0.001). Our findings indicate that in allergic patients nasal challenge with ragweed allergen induces a rise in complement activation in the nasal lavage fluid. These results highlight the role of the complement system in the allergic inflammation on the nasal mucosal surface.

No abstract