TNF-alpha and TNF-beta gene polymorphisms in Polish patients with sarcoidosis. Connection with the susceptibility and prognosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown aetiology, in which genetic factors, especially the genes of the highly polymorphic MHC region, seem to play an important role in the disease predisposition and course. The aim of this study was to evaluate the role of TNF genes polymorphism in sarcoidosis and to estimate possible association between these polymorphisms and susceptibility and prognosis of sarcoidosis. The analysis of -308G > A TNF-alpha gene (TNFA*1 and TNFA*2 alleles) and 252A > G TNF-beta gene polymorphisms (TNFB*1 and TNFB*2 alleles) were performed. METHODS: The study comprised of 130 sarcoidosis patients (75 subjects in the radiological stage I, and 55 in the stages II/III). Löfgren syndrome (LS) was manifested in 38 patients. After at least 3-years observation, 69 patients had remission, 24 subjects manifested persistent disease and 25 patients had progression. The control group consisted of 84 healthy subjects. The genotypes were determined using PCR-RFLP assay. RESULTS: The variant allele TNFA*2 was observed significantly more frequent in patients with Löfgren syndrome when compared to control group (OR = 2.301, C.I. = [1.23-4.32], chi2 = 6.91, p > 0.01), as well as to non-LS patients (OR = 2.167, C.I. = [1.17-4.01], chi2 = 6.22, p < 0.05). Moreover, the variant allele TNFA*2 was also observed significantly more frequent in patients with disease resolution than in patients with persistent disease and progression (OR = 3.53, C.I. = [1.66-7.50], chi2 = 11.65, p < 0.001). The variant allele TNF*2 was also overrepresented in patients with disease resolution after exclusion the patients with Löfgren syndrome (OR = 2.4, C.I. = [1-5.772], chi2 = 3.98, p < 0.05). There was no significant difference in TNF-A allele distribution between the control group and whole sarcoidosis group. The variant allele TNFB*1 was observed significantly more frequent in patients with disease resolution than in patients with persistent disease and progression. This difference was caused only by overrepresentation of TNFB*1 variant allele in Löfgren group. The significant differences in the distribution of TNFB*1 allele between the sarcoidosis an the control group was also noted (OR = 1,607, C.I. = [1,033-2,5], chi2 = 4.46, p < 0.05), but it was limited only to patients displaying Löfgren syndrome. CONCLUSION: Two alleles TNFB*1 and TNFA*2 of TNF gene are overrepresented in polish patients with Löfgren syndrome. The TNFA*2 allele is related with mild course of sarcoidosis in patients without LS.

[Diagnostic difficulties with pleural mesothelioma]. / Trudnosci w rozpoznawaniu miedzybloniaków zlosliwych oplucnej.

An increase in the incidence of mesothelioma is presently seen. The current views on pathogenesis and diagnosis of this malignancy are presented. Early and final diagnosis are hampered by heterogenecity of clinical, macroscopic and microscopic features of this tumor.

[The effect of fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) on results of spirometric measurements]. / Wplyw bronchofiberoskopii i plukania oskrzelowo-pecherzykowego (BAL) na wyniki badania spirometrycznego.

The effect of fiberoptic bronchoscopy and bronchoalveolar lavage on the functioning of the respiratory system was studied in 72 patients (42 males and 30 females). The bronchoscopy was performed in the sitting position. Supplemental oxygen was not given to all the evaluated patients. The group included 24 patients with lung cancer, 9 with sarcoidosis, 12 with tuberculosis, 1 with farmer's lung and 10 with other lung diseases (pneumonia, COPD). A control group consisted of 16 patients who were undergoing routine diagnostic endoscopy but who were seen to be without lung disease. Group BF (39 individuals) received only a bronchoscopic examination, group BF+BAL (33 persons) received a bronchoscopy followed by BAL using 140 ml. of normal saline solution as a lavage fluid. After the bronchoscopic examination there were significant differences in all spirometric measurements, except MEF25. The bronchoscopy and bronchoalveolar lavage caused a transient fall in FEV1, VC, MEF50, MEF75 (7.7-9.4%) which was similar in both groups. These measurements returned to normal after 24 hours. The testing of pulmonary functioning before the bronchoscopy was seen to be clinically important for safety of the patient undergoing this procedure.

[Phenotype of lymphocytes in bronchoalveolar lavage and peripheral blood with different clinical presentations of sarcoidosis]. / Fenotyp limfocytów z plukania oskrzelowo-pecherzykowego i krwi obwodowej w róznych postaciach klinicznych sarkoidozy.

The aim of this study was to investigate the relationship between the bronchoalveolar cell counts, the phenotypic characteristics of bronchoalveolar lavage and peripheral lymphocytes and the clinical manifestation of sarcoidosis. 24 patients with sarcoidosis of the lung were examined. Patients were divided into groups based on the presence and the type of clinical symptoms (patients with symptoms of Löfgren syndrome, with constitutional and respiratory symptoms and symptomless patients). The lymphocyte subtypes were analysed using the panel of monoclonal antibodies Simultest IMK Plus with the flow cytometry (Orto Cytoron Absolute). The highest ratio CD4/CD8 in BALF was found in patients with symptoms of Löfgren Syndrome (mean 11.4), the lowest in symptomless patients (mean 4.5). The bronchoalveolar cell count and the percentages of phenotypes of peripheral blood lymphocytes did not differ significantly between the groups of patients. The bronchoalveolar lavage performed in patients with sarcoidosis indicates various intensity of alveolitis dependent on the clinical manifestation.

Analysis of antioxidant enzyme activity and magnesium level in chronic obstructive pulmonary disease (COPD).

There is an increasing interest in the relationship of hypomagnesemia and oxidative stress in pulmonary diseases. It seems to be clinically relevant to assess prooxidant/antioxidant balance and its correlation with magnesium level in COPD. In this study, there were investigated the antioxidant enzymes activity and magnesium plasma level in a group of patients with chronic obstructive pulmonary disease and in the control group. The study group consisted of 41 patients admitted to hospital for ambulatory medical treatment in pulmonary department of the Medical University of Lublin. The control group was made up of 20 patients who were admitted for control examinations. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activity were assessed in red blood cells using kinetics methods. Significantly decreased activity of CAT in COPD, insignificantly decreased activity of GPX and insignificantly increased activity of SOD were detected. Patients with COPD also showed the lowered plasma magnesium level. The conclusion is that COPD is accompanied by a lowered magnesium level and an alteration in antioxidant status due to possible oxidative stress in this disease.

[Expression of IL-2 receptor in peripheral blood lymphocytes and bronchoalveolar lavage fluid (BAL) in patients with sarcoidosis]. / Ekspresja receptora dla IL-2 na limfocytach krwi obwodowej i plynu z plukania oskrzelowo-pecherzykowego (BAL) u chorych na sarkoidoze.

Interleukin 2 (IL-2) and its receptor (IL-2R) plays the important role in the lymphocytic alveolitis in sarcoidosis. The aim of this study was the comparative analysis of expression of IL-2 receptor subunits: alpha chain (IL-2R alpha) and beta chain (IL-2R beta) in peripheral blood and broncho-alveolar lavage fluid (BAL) in patients with sarcoidosis. We examined 18 patients (aged 23 to 47 years, 8 women and 10 men) with sarcoidosis and 5 healthy persons (the control group consisted of 2 women and 3 men, aged 25 to 39 years). The expression of IL-2R was evaluated by immunophenotyping in ORTHO Cytoron Absolute flow cytometer. Comparing the patients group to the control group, we found in BAL fluid of sarcoidosis patients statistically higher number of lymphocytes with IL-2R alpha and IL-2R beta expression (p < 0.002), when the percentage of these lymphocytes was similar in both groups. In peripheral blood of sarcoidosis patients comparing to control group, we noted higher percentage of lymphocytes with expression of IL-2R alpha and IL-2R beta (more evident difference concerned IL-2R beta) but without statistical significance. We also compared BAL fluid to peripheral blood in patients group. We found in BAL fluid lower percentage of lymphocytes with expression IL-2R beta (p < 0.02) and no significant changes in percentage and number of lymphocytes IL-2R alpha+. Our data concerning IL-2 and IL-2R suggest the activation of T lymphocytes in the lung in sarcoidosis. They present only little reflection of immunological reactions, which take place in sarcoidosis infant. The above study should be completed in future by evaluation of the other activation markers including IL-2R gamma.