[The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma and immunological processes in patients with type 2 diabetes and insulin resistance]. / Polimorfizm Pro12Ala genu receptora aktywowanego przez proliferatory peroksysomów gamma a procesy immunologiczne w cukrzycy typu 2 wiklanej insulinoopornoscia. Doniesienie wstepne.

INTRODUCTION: The peroxisome proliferator-activated receptor gamma (PPARgamma), a transcriptor factor, regulates immunological and metabolic processes, which are important for carbohydrate and lipid metabolism. Various polymorphic forms of PPARgamma may promote diabetes mellitus and diabetic complications. AIM OF THE WORK: The assessment of TNFalpha gene expression in peripheral blood monocytes, serum TNFalpha concentration and anti-GAD and ICA antibodies in relation to the polymorphism Pro12Ala in patients with 2 diabetes. PATIENTS AND METHODS: 58 patients with type 2 diabetes (average age 59.0 +/- 11 years) and 18 healthy people were examined. The Pro12Ala polymorphism of PPARy gene were assessed using mini-sequence technic SnaPshot [ABIPRISM-310]. The TNFalpha gene expression were estimated using real-time PCR [Applied Bio-systems]. The TNFalpha concentration [Quantikin Immunoassay, R&D Systems] and ICA and GAD antibodies [immunofluorescence method, DRG] were evaluated in venous blood. RESULTS: A heterozygotous genotype Pro12Ala was estimated in 32 patients and a homozygotous genotype Pro12Pro in 21. Only 6 patients were positive for GAD antibodies and only 6 patients for ICA antibodies. The TNFalpha concentration in serum and the TNFalpha gene expression in monocytes did not refer to the Pro12ala polymorphism of PPARy and neither to antibodies. CONCLUSION: 1) The TNFalpha concentration in serum and the TNFalpha gene expression in monocytes do not refer to the Pro12ala polymorphism of PPARgamma in patients with type 2 diabetes. 2) The Pro12Ala genotype do not influence autoimmunologic processes of diabetes.

[Serological markers of chronic Chlamydia pneumoniae and cytomegalovirus (CMV) infection in patients with peripheral occlusive artery disease--an initial report]. / Serologiczne wykladniki przewleklego zakazenia Chlamydia pneumoniae i Cytomegalowirusem (CMV) u chorych na miazdzyce zarostowa--doniesienie wstepne.

Involvement of infection agents in pathogenesis of atherosclerosis was described in several studies, particularly in patients with acute coronary syndrome or ischemic stroke. However, in very few studies an association of serological markers of chronic infection with peripheral occlusive artery disease was analysed. The prevalence and concentration of immunoglobulin G and A to Chlamydia pneumoniae and immunoglobulin G to CMV were measured in sera of 31 participants suffering from peripheral occlusive artery disease. Significant difference in the prevalance of immunoglobulin G to C. pneumoniae and CMV between study and control groups was documented. There was no such association in reference to immunoglobulin A to C. pneumoniae index. Serum concentration of all measured antibodies were significantly higher in the study group than in control.

Vasculitis in systemic lupus erythematosus (SLE)--assessment of peripheral blood mononuclear cell activation and the degree of endothelial dysfunction: initial report.

BACKGROUND: Inflammatory-immune changes in the vascular endothelium are one of the main factors initiating vessel wall damage. Enhanced expression of endothelial adhesion molecules and their receptors on the surface of circulating leukocytes seems to play an important role in the pathogenesis of vasculitis. Increasing evidence indicates endothelial cell activation/damage in SLE. In patients with SLE complicated by vasculitis, enhanced expression of integrin activation markers on the surface of peripheral blood mononuclear cells (PBMCs) has been reported. It seems relevant to assess the mechanisms of inflammatory response involving PBMCs and endothelial cells at particular stages of SLE microangiopathy. AIM: The main aim was to assess the surface expressions of the integrin adhesion molecules VLA-4 (CD49d) and LFA-1 (CD11a) on PBMCs as well as the number of circulating endothelial cells (CECs) in patients with SLE and complications related to inflammatory microangiopathy and to determine whether these parameters vary depending on disease activity. PATIENTS: Twenty-nine women with SLE (mean age: 38.72+/-10.23 years) were divided into subgroup I: those with severe disease activity according to the modified disease activity index SLEDAI, characterized by the presence of inflammatory microangiopathy-related complications such as systemic central nervous system affection and/or vasculitis and/or nephritis (15 women, mean age: 38.33+/-11.02 years), and subgroup II: patients with mild or moderate disease activity according to SLEDAI and without vascular complications (14 women, mean age: 39.14+/-9.72 years). METHODS: Expressions of VLA-4 and LFA-1 on the surface of peripheral blood lymphocytes and monocytes were assessed by flow cytometry using monoclonal antibodies. CECs (a marker of endothelial damage) were isolated from peripheral blood with anti-CD146(S-Endo 1)-coated immunomagnetic Dynabeads. Tests for the lupus anticoagulant, antinuclear antibody, anti-dsDNA, and anticardiolipin antibody were performed in every study subject by ELISA. Erythrocyte sedimentation rate and serum levels of fibrinogen, C-reactive protein, the complement components C3 and C4, urea, creatinine, and uric acid were determined by standard methods. Peripheral blood counts and a general urinalysis were also performed. RESULTS: The mean CEC count was significantly higher in SLE patients than in the control group (15.29+/-12.10 vs. 3.08+/-1.46 cells/ml, p<0.001). CEC counts was notably elevated in patient subgroup II compared with the control group (9.14+/-5.16 vs. 3.08+/-1.46 cells/ml, p<0.05) and in subgroup I compared with subgroup II (21.03+/-13.96 vs. 9.14+/-5.19 cell/ml, p<0.05). In patients with severe SLE flares, CEC count visibly correlated with disease activity assessed by SLEDAI score (R=0.92, p<0.001). The expressions of VLA-4 and LFA-1 on peripheral blood lymphocytes in both patient subgroups were significantly higher than in the control group (subgroup I vs. controls: 1.70+/-1.56 vs. 0.39+/-0.26%, p<0.05, and 1.97+/-2.60 vs. 0.67+/-0.83%, p<0.05; subgroup II vs. controls: 1.71+/-1.04 vs. 0.39+/-0.26%, p<0.001, and 3.32+/-2.48 vs. 0.67+/-0.83%, p<0.05, for VLA-4 and LFA-1, respectively). There was no significant difference between the two subgroups of patients (1.70+/-1.56 vs. 1.71+/-1.04%, p>0.05, and 1.97+/-2.60 vs. 3.32+/-2.48%, p>0.05, respectively). Similarly, the surface expression of LFA-1 on circulating monocytes in patients in both subgroups was notably enhanced over that of the control group (91.44+/-16.00 vs. 84.95+/-19.86%, p<0.05, and 90.11+/-10.34 vs. 84.95+/-19.86%, p<0.05, in subgroups I and II respectively) and was comparable in both subgroups of patients (91.44+/-16.00 vs. 90.11+/-10.33%, p>0.05). The surface expression of VLA-4 on peripheral blood monocytes was considerably higher in patients with severe disease activity than in the control group and in patients with less active disease (77.10+/-13.56 vs. 64.90+/-19.13%, p<0.05, and 77.10+/-13.56 vs. 63.40+/-20.95%, p<0.05, respectively). However, there was no significant difference between patients with mild or moderate disease activity and the control group (63.40+/-20.95 vs. 64.90+/-19.13%, p>0.05). CONCLUSIONS: 1) The number of CECs increases in the course of SLE and correlates with disease activity, indicating progressive endothelial damage.2) The expressions of VLA-4 and LFA-1 on the surface of peripheral blood lymphocytes as well as that of LFA-1 on circulating monocytes are enhanced in SLE patients regardless of disease activity. 3) The expression of VLA-4 on the surface of circulating monocytes is enhanced only in patients with severe disease activity, characterized by the presence of complications connected with inflammatory microangiopathy, which may indicate that the upregulation of VLA-4 expression in monocytes plays a leading role in the pathogenesis of vasculitis in SLE.