Correlates of D-dimer in older persons.

BACKGROUND AND AIMS: D-dimer is a marker of active fibrinolysis. Understanding how age-related factors affect D-dimer levels may help the interpretation of high D-dimer levels in older individuals. METHODS: 776 Baltimore Longitudinal Study on Aging (BLSA) participants (mean age 68.4+/-13.9 yrs) were divided into three groups according to baseline D-dimer levels >200 ng/mL; 100-200 ng/mL and <100 ng/mL. RESULTS: D-dimer level increased with age (p<0.0001). Using polychotomous logistic regression models, we found that age, cholesterol, triglycerides, creatinine, erythrocyte sedimentation rate, hemoglobin and body mass index were independently associated with D-dimer level. CONCLUSIONS: Rising levels of D-dimer with age can be explained in part by the high prevalence of pro-inflammatory conditions and increasing burden of lipid abnormalities, anemia and obesity. These factors compromise the specificity of D-dimer levels as a diagnostic aid to thrombosis in older individuals.

Cytokine-induced killer cells targeted by the novel bispecific antibody CD19xCD5 (HD37xT5.16) efficiently lyse B-lymphoma cells.

Due to their dual binding capacity, bispecific antibodies (bsAb) can be used to cross-link cytotoxic effector cells with malignant targets and may thereby improve adoptive immunotherapy. In this study, the development and preclinical testing of the quadroma-derived bsAb HD37xT5.16 of the specificity CD19xCD5 is reported. Effector cells used were a population of ex vivo expanded and activated T cells called cytokine-induced killer (CIK) cells expressing CD5. When combined with CIK cells, the cytolytic potency of HD37xT5.16 against CD19 positive B cell lymphoma lines was comparable to that observed with a previously described CD19xCD3 bsAb. Further on, we could demonstrate that bsAb CD19xCD5, in contrast to its CD3-binding counterpart, does not induce proliferation of resting T cells and causes only little activation-induced cell death. Therefore, this novel bsAb binding effector T cells via CD5 may be particularly useful in combination with adoptive transfer of ex vivo activated T cells, e.g., in the setting of adoptive immunotherapy after allogeneic stem cell transplantation. The in vitro studies outlined here support the experimental use of bsAb HD37xT5.16 in preclinical in vivo models for evaluation of its safety and efficacy profile.

Cytokine-induced killer cells against autologous CLL: direct cytotoxic effects and induction of immune accessory molecules by interferon-gamma.

Cytokine-induced killer cells (CIK cells), coexpressing CD3 and CD56, can be expanded from peripheral blood mononuclear cells by the timed addition of interferon-gamma (IFN-gamma), IL-2 and OKT3. The effects of CIK cells on primary, autologous CLL cells are described. We used MACS to separate CD3(+) cells for expansion of CIK cell effectors and CD19(+) targets from peripheral blood of 16 CLL patients. Apoptosis was assessed by measuring annexinV staining in CLL cells. After incubation of autologous CIK with CLL, specific apoptosis in CLL cells was 15%. Coincubation with irradiated CIK cells for 48 hr before adding vital CIK cells resulted in an increased ICAM-1 expression on CLL cells and an increase in apoptosis of CLL targets (30%). These effects were mediated by IFN-gamma secretion of CIK cells. In addition to their direct cytotoxic effect, CIK cells secrete IFN-gamma that modulates the expression of adhesion molecules on CLL cells, and this enhances apoptosis induction by cytotoxic effector cells.