Although strong evidence exists linking fasting plasma levels of LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) to risk for development of coronary artery disease (CAD), the data in support of an independent role for fasting triglyceride (TG) concentrations are weak. Humans are in the postprandial state most of the day, however, and results from both basic and clinical studies suggest that postprandial TG levels may be atherogenic. Previous studies have not, however, attempted to determine if postprandial TG levels are associated with CAD independent of other traditional risk factors or plasma lipid levels, particularly fasting plasma concentrations of TG and HDL-C. Ninety-two men and 113 women (mean age, 51.6 and 53.6 years, respectively) were recruited from populations undergoing diagnostic exercise electrocardiographic or thallium stress tests at our medical centers. Twenty-six men and 24 women had positive tests. We chose exercise-induced myocardial ischemia (EIM) as the criterion for defining case and control subjects because we wanted participants who did not have a prior diagnosis of CAD. Blood samples were obtained for measurement of plasma TG, TG-rich lipoprotein TG, and retinyl palmitate (RP) levels 2, 3.5, 5, and 8 hours after the subjects had consumed a fatty test meal. Logistic regression models were developed to test for associations between each variable and case-control status. Among men but not women postprandial TG and RP responses were associated with EIMI independent of age, race, and smoking status. In the male group, the odds ratio (OR) for an increase in postprandial TG response of approximately 1 SD was 1.69 (P = .007); the OR for an increase in RP response of 1 SD was 2.47 (P = .011). However, when fasting TG was added to the model, the OR for postprandial TG area in the men was reduced to 1.44 (P = .17); the OR postprandial RP area in the men was reduced to 1.88 (P = .12). There was no effect of adding other risk factors, including LDL-C and HDL-C, to the model. Significant effect modification by body mass index (BMI) on the relationship between postprandial responses and case-control status was observed. In men with BMI < 30, the OR was 1.83 for postprandial TG (P = .041) and 2.77 for postprandial RP (P = .032) in models that included fasting TG, LDL-C, and hypertension.

We have shown previously that the Rhesus (Rh) polypeptides are the commonest targets for pathogenic anti-red blood cell (RBC) autoantibodies in patients with autoimmune hemolytic anemia (AIHA). The aim of the current work was to determine whether activated T cells from such patients also mount recall responses to epitopes on these proteins. Two panels of overlapping 15-mer peptides, corresponding to the sequences of the 30-kD Rh proteins associated with expression of the D and Cc/Ee blood group antigens, were synthesized and screened for the ability to stimulate the in vitro proliferation of mononuclear cells from the peripheral blood or spleen of nine AIHA cases. Culture conditions were chosen that favor recall proliferation by previously activated T cells, rather than primary responses. In seven of the patients, including all four cases with autoantibody to the Rh proteins, two or more peptides elicited proliferation, but cells from eight of nine patients with other anemias and seven of nine healthy donors failed to respond to the panels. Multiple peptides were also stimulatory in two positive control donors who had been alloimmunized with Rh D-positive RBCs. Six different profiles of peptides elicited responses in the AIHA patients, and this variation may reflect the different HLA types in the group. Stimulatory peptides were identified throughout domains shared between, or specific to, each of the related 30-kD Rh proteins, but T cells that responded to nonconserved regions did not cross-react with the alternative sequences. Anti-major histocompatibility complex class II antibodies blocked the responses and depletion experiments confirmed that the proliferating mononuclear cells were T cells. Notably, splenic T cells that proliferated against multiple Rh peptides also responded to intact RBCs. We propose that pathogenic autoantibody production in many cases of AIHA is driven by the activation of T-helper cells specific for previously cryptic epitopes on the Rh proteins.