Presence of autoantibodies to apolipoprotein A-1 in patients with acute coronary syndrome further links autoimmunity to cardiovascular disease

Anti-apolipoprotein A-1 (Apo A-1) autoantibodies were described in autoimmune disorders such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and might be involved in the genesis of arterial and venous thrombotic events. To investigate the presence of these autoantibodies in patients with acute coronary syndrome (ACS) without other features of autoimmunity, we set up an enzyme-linked immunosorbent assay (ELISA) for anti-Apo A-1 antibodies. We used it to investigate their prevalence in ACS as compared to SLE and APS and correlated them to plasma Apo A-1 and serum amyloid A protein (SAA) concentrations. The prevalence of anti-Apo A-1 autoantibodies in the healthy control group was 1% (1/92), but was significantly higher in other groups: 21% (11/53) in ACS group (P=0.001), 13% (12/92) in SLE and/or APS group (P=0.005). Multiple linear regression revealed a significant correlation between plasma Apo A-1 (r=-0.72, P=0.013), plasma SAA concentration (r=0.76, P=0.0066) and anti-Apo A-1 IgG titre in ACS patients. The presence of anti-Apo A-1 autoantibodies in patients with ACS highlights an additional link between autoimmunity, inflammation and atherosclerosis.     

Perceptual speed does not cause intelligence, and intelligence does not cause perceptual speed

There is ongoing debate whether the efficiency of local cognitive processes leads to global cognitive ability or whether global ability feeds the efficiency of basic processes. A prominent example is the well-replicated association between inspection time (IT), a measure of perceptual discrimination speed, and intelligence (IQ), where it is not known whether increased speed is a cause or consequence of high IQ. We investigated the direction of causation between IT and IQ in 2012 genetically related subjects from Australia and The Netherlands. Models in which the reliable variance of each observed variable was specified as a latent trait showed IT correlations of -0.44 and -0.33 with respective Performance and Verbal IQ; heritabilities were 57% (IT), 83% (PIQ) and 77% (VIQ). Directional causation models provided poor fits to the data, with covariation best explained by pleiotropic genes (influencing variation in both IT and IQ). This finding of a common genetic factor provides a better target for identifying genes involved in cognition than genes which are unique to specific traits.     

Generation of potent T(h)1 responses from patients with lymphoid malignancies after differentiation of B lymphocytes into dendritic-like cells

Dendritic cells (DC) are a group of potent antigen-presenting cells (APC) specialized for initiating T cell immune responses. They originate from the bone marrow and upon stimulation with bacterial products, cytokines or CD40 ligation they acquire the ability to migrate to the secondary lymphoid organs. In vitro DC can be generated from human CD34(+) bone marrow cells and CD14(+) peripheral blood monocytes after culture with different cytokine combinations. Since most leukemic cells and tumors in general are devoid of APC capacities, various strategies have been used to increase their recognition and confer the capacity of antigen presentation on them. Because of our interest in the design of vaccine immunotherapy protocols for the adjuvant treatment of patients with lymphoid malignancies (LM), we chose to explore the capacity of human acute lymphoblastic leukemia, chronic lymphocytic leukemia and plasma cell leukemia to differentiate into cells with APC and DC features. Our results among a sample of 10 patients demonstrate that such approach is feasible. Leukemic cells could be induced in the presence of IL-4 and CD40L to exhibit a DC morphology with a phenotype of mature DC-like cells. They could also induce a potent proliferative response in naive CD4(+) T cells. In addition, they expressed chemokine receptor CCR7 and CD62L, and could drive T cells towards a T(h)1 response with secretion of IFN-gamma. Our strategy leading to increased LM cell immunogenicity may have potential clinical applications and LM appear to be attracting candidates for adjuvant vaccination and adoptive immunotherapy.     

Effects of green tea polyphenols on murine transplant-reactive T cell immunity

Green tea polyphenols (GrTP), the active ingredient of green tea, may have immunosuppressive properties, but whether and how GrTP affect transplant-reactive T cells is unknown. To address this, we tested the effects of GrTP on in vitro and in vivo transplant-reactive T cell immunity. GrTP inhibited IFNgamma secretion by cultured monoclonal T cells and by alloreactive T cells in mixed lymphocyte reactions. Oral GrTP significantly prolonged minor antigen-disparate skin graft survival and decreased the frequency of donor-reactive interferon gamma-producing T cells in recipient secondary lymphoid organs compared to controls. In contrast to other hypothesized actions, oral GrTP did not alter dendritic cell trafficking to lymph nodes or affect metalloproteinase activity in the graft. This is the first report of an immunosuppressive effect of GrTP on transplant-reactive T cell immunity. The results suggest that oral intake of green tea could act as an adjunctive therapy for prevention of transplant rejection in humans.     

Healthy monozygous twins do not recognize identical T cell epitopes on the myelin basic protein autoantigen

The T cell response against myelin basic protein (MBP) has been extensively studied in humans because of its putative role in the pathophysiology of multiple sclerosis (MS). Higher concordance rates in monozygous twins as well as an increased risk in relatives suggest the role of genetic factors in MS susceptibility. Very little is known about the shaping of T cell repertoire towards self antigens in humans and their contribution to disease susceptibility in autoimmune disorders. Here we report the comparative T cell epitope recognition patterns towards the MBP auto-antigen in healthy identical twins. We have established MBP-specific T cell lines from eight sets of twins and characterized their fine epitope specificity. Intra-pair comparison showed the co-existence of shared as well as distinct epitopes in six of eight pairs and a complete absence of concordant epitope recognition within two other pairs. These findings indicate that important differences in T cell repertoires against a self antigen may be observed between genetically identical healthy individuals, rendering difficult the interpretation of the differences which may be observed between identical twins discordant for an autoimmune disease.     

Visualization of erythrocyte membrane antigen by means of fluorescent microspheres coupled to monoclonal mouse auto-antibody: Distribution of this antigen among species

Mouse peritoneal cells (PC) in culture produce auto-antibodies lyzing bromelain-treated mouse erythrocytes (MRBCbr). These auto-antibodies have been obtained in an homogeneous form in substantial amounts after cell fusion of PC with myeloma X63.Ag8. They have been identified as the anti-Hb-auto-antibodies described by us in 1980. Once coupled to fluorescent microspheres (Ms), they were used to detect the corresponding antigen. It was found that the specific antigen was not only present on the surface of all MRBCbr but also, in a much smaller proportion, on some normal MRBC. Its distribution is not restricted to the mouse: pigeon RBC is stained heavily; human red cells give, more or less, positive reaction, according to their blood group. Some species, as horse RBC, are consistently negative. The opportunity offered by the fluorescent microspheres technique to trace the antigen recognized by the Hb-auto-antibody in the mouse tissues and on cells from other species should lead to a better understanding of the cross-antigenicity of many RBC and of the peculiar auto-immune process involving MRBCbr in the mouse.     

ThinPrep evaluation of fluid samples aspirated from cystic ovarian masses

The cytological evaluation of ovarian cystic fluid using ThinPrep has not been reported. To determine the diagnostic accuracy of ThinPrep cytology in distinguishing between benign and nonbenign ovarian cystic lesions, we examined 65 fluid samples aspirated during intraoperative consultation with subsequent histologic correlation. One ThinPrep slide was prepared from each sample aspirated from surgically removed ovarian cystic masses and reviewed blindly by a panel of three cytopathologists. The parameters used in cytological evaluation were cellularity, cell types, cellular arrangement, and background. Four samples were acellular and excluded from the study. The consensus cytologic diagnoses were compiled for 61 cases which were assigned to one of the following diagnostic categories: negative for malignant cells (40 cases), atypical cytology (13 cases), and suspicious or positive for malignancy (8 cases). Histologic correlation of the cytological benign/negative cases showed that 26/40 (65%) were histologically benign and 14/40 were false-negative (35%, 5 carcinomas and 9 borderline tumors) with 10 of these cases being mucinous tumors. Most false-negative cytologic samples (11/14 or 79%) did not have an epithelial component. Of the 21 cytological nonbenign diagnoses (atypical/suspicious/positive), 15 (71%) were confirmed on histology (10 carcinomas and 5 borderline tumors). However, a nonbenign cytologic diagnosis was rendered in 6 histologically benign cases, including 2 serous cystadenomas, 1 mucinous cystadenoma, 1 serous cystadenofibroma, 1 endometriosis, and 1 corpus luteal cyst. The diagnostic sensitivity by ThinPrep evaluation of ovarian cystic masses is 81% (26/32) for benign and 52% (15/29) for nonbenign lesions. Our results concluded that ThinPrep examination of ovarian cystic fluid is not accurate in distinguishing benign from malignant cysts, given the significant number of false-negative diagnoses. Major contributing factors include sparse cellularity of the fluid samples and mucinous differentiation of the tumors.