No evidence for linkage between the hereditary angiooedema clinical phenotype and the BDKR1, BDKR2, ACE or MBL2 gene.

Hereditary angiooedema (HAE) is a life-threatening disease with poor clinical phenotype correlation with its causal mutation in the C1 inhibitor (SERPING1) gene. It is characterized by substantial symptom variability even in affected members of the same family. Therefore, it is likely that genetic factors outside the SERPING1 gene have an influence on disease manifestation. In this study, functional polymorphisms in genes with a possible disease-modifying effect, B1 and B2 bradykinin receptors (BDKR1, BDKR2), angiotensin-converting enzyme (ACE) and mannose-binding lectin (MBL2), were analysed in 36 unrelated HAE patients. The same analysis was carried out in 69 HAE patients regardless of their familial relationship. No significant influence of the studied polymorphisms in the BDKR1, BDKR2, ACE and MBL2 genes on overall disease severity, localization and severity of particular attacks, frequency of oedema episodes or age of disease onset was detected in either group of patients. Other genetic and/or environmental factors should be considered to be responsible for HAE clinical variability in Caucasians.

Continuous venovenous hemofiltration: effects on monocyte and lymphocyte immunophenotype in critically ill patients.

The aim of this study was to test the hypothesis that continuous venovenous hemofiltration (CVVH) increases HLA-DR expression on monocytes and T lymphocytes in critically ill patients. 24 septic (SP) and 10 non-septic (NSP) medical ICU patients with acute renal failure were studied prospectively. The ultrafiltration rate was 20-30 ml.kg(-1).h(-1). The total and differential white cell counts were measured and CD3+ lymphocyte count, HLA-DR expression on CD14+ monocytes and CD3+ lymphocytes were analysed by two-colour flow cytometry before, 4 and 24 h after CVVH initiation, respectively. CVVH did not influence leukocyte, granulocyte, total lymphocyte and CD3+ lymphocyte counts in both groups of patients. The percentage of HLA-DR+/CD14+ monocytes in SP revealed no changes, whereas it decreased after 4 h of CWH in NSP (p < 0.05). The percentage of HLA-DR+/CD3+ lymphocytes in SP decreased after 24 h (p < 0.05), whereas it remained unchanged in NSP. We conclude that CWH initiation is not associated with the increase of HLA-DR expression on CD14+ monocytes and T lymphocytes in critically ill patients with acute renal failure.

[Organ-specific antibodies in children with idiopathic inflammatory bowel disease and their use in clinical practice]. / Orgánove specifické protilátky u detí s idiopatickými strevními zánety a jejich uzití v klinické praxi.

BACKGROUND: Ethiopathogenesis of the idiopathic inflammatory bowel disease has not been yet fully explained. Several abnormalities of the humoral immunity supporting the concept of autoimmune character of the disease have been identified. The aim of our study was to characterise occurrence of the organ specific antibodies against the intestinal goblet cells and against acinar cells of the exocrine pancreatic tissue and to evaluate their significance for the diagnostics of the idiopathic inflammatory bowel disease. METHODS AND RESULTS: 69 children were included in the study. The group consisted of 20 patients with idiopathic proctocolitis (11 boys and 9 girls, 6 to 18 years old, average age 15.5) and 14 patients with Crohn's disease (9 boys and 5 girls, 5 to 18 years old, average age 14.7). Control group included 35 children (20 boys and 15 girls, average age 14.7). In patients of the idiopathic proctocolitis group, antibodies against the intestinal goblet cells were assayed by indirect immunofluorescence method in 55%. In patients with Crohn's disease, antibodies against acinar cells of the exocrine pancreatic tissue were found in 64.2%. Differences in manifestation of antibodies against acinar cells of the exocrine pancreatic tissue in Crohn's disease were statistically significant (p = 0.001). Statistically significant (p = 0.01) was also the difference of levels of antibodies against the intestinal goblet cells in patients with idiopathic proctocolitis when compared to patients with Crohn's disease. Statistically significant difference (p = 0.01) was found in levels of antibodies against acinar cells of the exocrine pancreatic tissue in Crohns disease and antibodies against the intestinal goblet cells in patients with idiopathic proctocolitis. CONCLUSION: Testing on presence of specific antibodies against acinar cells of the exocrine pancreatic tissue and against intestinal goblet cells is a valuable tool for the diagnostics of the idiopathic inflammatory bowel disease in childhood and adolescence.

Histamine increases the level of IFNγ produced by HIV-1 specific CTLs and this production depends on total IgE level.

BACKGROUND: The HIV (human immunodeficiency virus) population remains a global concern whose treatment is effective, though not yet optimal. Immune based therapies have thus far been disappointing and still need to be explored further. Based on published data suggesting that the functions of cytotoxic CD8+ T lymphocytes (CTL) can be improved by histamine, we investigated the effect of histamine in vitro on HIV-1 specific CD8+ T lymphocytes in HIV+ subjects. RESULTS: 60 HIV+ subjects were included in the study. We evaluated CTL function by IFNγ (interferon gamma) production (using the enzyme-linked immunospot assay (Elispot), BD Bioscience). Changes in the production of IFNγ after incubation with histamine were compared with the levels of total IgE (immunoglobulin E, measured using a Dade Behring analyzer), because histamine is endogenously released through IgE. Activation of HIV-specific CTL by histamine occurs via H2R (histamine receptors). Thus we attempted to block this activation using cimetidine (antagonist H2R). CONCLUSIONS: We found an increase in IFNγ production after the activation of HIV-1 specific CD8+ T lymphocytes by histamine (this elevation was blocked by cimetidine), furthermore, we demonstrated a negative correlation between the production of IFNγ and levels of total IgE.