Prevalence of factor V Leiden mutation in various populations.

Resistance to activated protein C (APC) is the most common inherited risk factor for venous thrombosis. Most cases of APC resistance are caused by the point mutation nt 1691 G-A in factor V gene, referred to as factor V Leiden mutation. As initially shown in a Dutch population, this mutation has a carrier rate of 2.9%, the most frequent genetic disposition for thrombophilia and deep venous thrombosis. By large-scale epidemiological studies we have determined the prevalence of factor V Leiden mutation in populations from Poland (200), Argentina (215), Venezuela (126), Costa Rica (196), and India (150). The prevalences have been estimated for Poland (Warsaw) 5.0%, Argentina (Buenos Aires) 5.1%, Venezuela (Valencia) 1.6%, Costa Rica (San José) 2.0%, and India (Punjab) 1.3%. Based on worldwide distribution, it can be hypothesized that the factor V Leiden mutation has originated and accumulated in central European Caucasians and spread over the world by migration.

Large-scale screening for factor V Leiden mutation in a north-eastern German population.

Preliminary epidemiological data showed a high but varying prevalence of factor V Leiden mutation in various European populations. To analyze population differences statistically and generate reliable evaluation criteria for morbidity estimates, large numbers of unselected probands from different populations have to be tested. A convenient, efficient, reliable and cost efficient method for large-scale screening of factor V Leiden mutation has been developed using capillary blood samples soaked onto filter paper cards for the detection of mutations by heteroduplex analysis. Screening 1,628 alleles of a north-eastern German population by this procedure revealed an allele frequency of 3.56% (carrier rate 7.12%) which is significantly higher than those published for Italy and the Netherlands. Differences in allele frequencies compared to other European populations could statistically not be proved based on the small size of the published samples.

Macrophages are dispensable for superantigen-mediated stimulation and anergy induction of peripheral T cells in vivo.

Bacterial superantigens provoke T lymphocyte activation by cross-linking the variable part of the T cell receptor (TCR) beta-chain with MHC class II molecules on antigen-presenting cells. Although the molecular mechanisms of this interaction are well characterized, the in vivo accessory cell requirements for this stimulation of T lymphocytes by bacterial superantigens remain unknown. In the present study we have addressed the role of splenic macrophages in the activation of V beta 8+ peripheral T cells by staphylococcal enterotoxin B (SEB) in BALB/c mice. SEB-triggered clonal expansion and subsequent induction of unresponsiveness of both CD4+ and CD8+ T cells were investigated in naive animals, or in mice injected intravenously with dichloromethylene diphosphonate-containing liposomes. Such a treatment resulted in the complete and long-lasting elimination of the splenic macrophage population. Remarkably, however, this complete depletion of peripheral macrophages had only a rather minor effect on the superantigen-induced T cell response in the spleen, and macrophage-depleted animals exhibited overall the same magnitude and kinetics of SEB-mediated T cell activation and anergy-induction as their nondepleted counterparts. Our data thus exclude an essential role of peripheral macrophages or macrophage-secreted cytokines in the systemic T cell activation caused by bacterial superantigens in vivo.