Haptoglobin genotype 2-2 associated with atherosclerosis in patients with ischemic stroke.

AIM: Ischemic stroke (IS) is multifactorial disease and therefore different genes and proteins play a role in its development. Haptoglobin (Hp) removes free hemoglobin and protects from iron-induced oxidative damage, inflammatory response, atherosclerosis and cerebrovascular diseases. The aim of this study was to investigate Hp genetic variants in patients with carotid atherosclerotic lesions and IS. MATERIAL AND METHODS: A total of 121 subjects with IS participated in the study, 81 male and 40 female. RESULTS: Among 121 patients with IS, 79 had diffuse atherosclerotic plaques and stenosis. Hp genotype was statistically significantly associated with CDFI neck carotid artery stenosis findings (p = 0.006). Patients with Hp1-2 genotype had statistically significantly larger odds for atherosclerotic changes compared to those with Hp1-1 genotype, as well as those with Hp2-2 genotype. CONCLUSION: This study has shown an association of the Hp2-2 genotype and atherosclerosis in patients with IS, indicating Hp2-2 genotype as a genetic biomarker for precision medicine and personalized healthcare.

Serotonin transporter gene polymorphisms: Relation with platelet serotonin level in patients with primary Sjogren's syndrome.

Significantly lower platelet serotonin level (PSL) in patients with primary Sjogren's syndrome (pSS) than in healthy controls has been reported in our prior studies. In the present report, we demonstrated effect of functional polymorphisms in the serotonin transporter gene (5-HTT) on PSL. We describe a group of 61 pSS patients and 100 healthy individuals subjects, who received PSL measurement in our prior study. All subjects were genotyped for the promoter 5-HTTLPR (L/S), rs25531 (A/G) and intronic 5-HTTVNTRin2 (l/s) polymorphisms. Overall, the presence of 5-HTTVNTRin2 ss genotype was associated with significantly lower PSL in pSS patients, not in healthy controls. Reduced PSL in pSS patients is in line with hypothesis of association between chronic immunoinflammation and 5-HT system dysregulation, identifying additional mechanisms such as altered 5-HT transport as potential genetic factor contributing to PSL depletion.

[Etiopathogenesis of progressive systemic sclerosis]. / Etiopatogeneza progresivne sistemne skleroze.

Progressive systemic sclerosis (PSS) is a systemic disease of connective tissue involving the skin and internal organs characterized by fibrotic and degenerative changes. The disease is usually progressive, incurable and always leads to death. Several hypotheses about the etiopathogenesis of PSS exist which try to explain the cause of morphological changes of the connective tissue. The first theory advocates evolution of the primary lesion within the blood vessels, the second considers the primary event to be an abnormality of collagen metabolism manifested by fibrosis. The third postulates on an autoimmune basis for the disease, and the fourth is based on the disfunction of autonomic nervous system. All the theories are partly linked and represent the morphological, biochemical and immunological aspects of the pathogenesis of this disease.

[Tuberculosis in systemic connective tissue diseases]. / Tuberkuloza u tijeku sistemskih bolesti vezivnog tkiva.

Six female patients who developed tuberculosis during the treatment of connective tissue diseases are presented. Underlying disease--systemic lupus erythematosus, rheumatoid arthritis, and polymyositis--with its numerous immunopathologic processes essentially decreases resistance of the organism to infections. Tuberculosis usually accompanies chronic, exhausting diseases and tends to involve patients with the decreased immunity. The use of glucocorticoids and immunosuppressive agents has been shown to have a significant influence on the suppression of the immune system. Thus, tuberculosis is a dangerous, very often fatal complication in the course and treatment of connective tissue diseases.

[Intermittent intravenous cyclophosphamide application in patients with systemic lupus erythematosus]. / Intermitentna intravenska primjena ciklofosfamida u bolesnika sa sustavnim eritemskim lupusom.

The aim of this paper is retrospective analysis of data from patients in whom the indication for cyclophosphamide (CF) pulse therapy was established in our department. Indications for CF pulse treatment were lupus nephritis (LN) alone or associated with central nervous system lupus. CF was administred in the dose of 500-1000 mg/m2 intravenously once monthly for the 6 months and once every 3 months thereafter. Patients were treated with adequate dose of glucocorticoids and other symptomatic therapy. The effect of applied therapy has been analysed by monitoring proteinuria, serum creatinine concentration, creatinine clearance, ESR, ANF titer and total complement hemolytic activity. Initial therapeutic procedure has been completed in 25/30 patients. The reasons for discontinuation in 5/30 patients were as follows: end-stage renal failure in spite of therapy (1), psychosis and lost of compliance (1), recurrent pancytopenia and subsequent sepsis (1), death non related to SLE (1) and failure to show at follow-up (1). Significant improvement of all control parameters was observed in the majority of patients in whom the therapy was completely conducted. 16/25 patients continued therapy for the next 18 months and in only 1/16 patients therapy was discontinued because of end-stage renal failure. In other 15/16 patients further improvement of control parameters was observed, although not so expressed as in the first 6 months. The most frequent complications were infections (16 infections were microbiologically proved and there were probably more infections). Alopecia (2), haematuria (1) and amenorrhoea (1) were also observed. Relatively low incidence of complications may be explained by careful patient monitoring. Considering that therapeutic success is defined not only by the improvement of renal function, but by stopping of further progression of renal failure, it can be concluded that intermittent CF pulse therapy showed good effect on LN in patients with clear indication.

Natural killer cell number and activity in remission phase of systemic connective tissue diseases.

The proportions and numbers of peripheral blood mononuclear cell markers and peripheral blood NK cell activity were analyzed and correlated in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SS) patients in the remission phase of the diseases. In comparison to the control data, the number of CD56+ cells was significantly increased in RA patients only; the same held true for double-positive cells, i.e., the alterations did not distinguish various subpopulations of NK cells. NK cell activity was significantly decreased in all the three groups of patients, with the complete lack of correlation between the NK cell number and their activity. It is possible that a significantly diminished NK cell activity in these diseases provokes a compensatory production of nonfunctional NK cells.

Peripheral blood CD5+ B cell subset in the remission phase of systemic connective tissue diseases.

OBJECTIVE: To get a better insight into the level of circulating CD5+ B cells as related to the systemic connective tissue disease activity. METHODS: Peripheral blood CD5+CD19+ cells of patients in the remission phase of systemic lupus erythematosus (SLE) (n = 28), Sjögren's syndrome (SS) (n = 20), rheumatoid arthritis (RA) (n = 26), and 19 control healthy subjects were analyzed by 2-color flow cytometry. RESULTS: In comparison to control group, the patients with SLE had a significant increase in the relative CD19+CD5+ blood cell count (p < 0.0005); this count was also different from the finding in both RA (p < 0.005) and patients with SS (p < 0.05). In contrast, the proportion of B cells expressing CD5 (within an individual B cell population) was significantly increased in all the 3 diseases compared to healthy subjects (SLE, p < 0.0001; SS, p < 0.05; and RA, p < 0.01). In the multivariate discriminant analysis, a discriminant function defined by the CD19+CD5+ subset strongly discriminated SLE, SS and RA from the control, but also SLE from both SS and RA. CONCLUSION: Our findings demonstrated that, in relation to healthy control subjects, the blood CD5+ B subset tended to be elevated in the patients in the remission phase of systemic connective tissue diseases, particularly in SLE.

Binding of anti-double stranded (ds) DNA-positive sera to denatured (d) DNA and synthetic poly[dA-dT] x poly[dA-dT] double stranded copolymer in an ELISA format.

Using an ELISA assay anti-nuclear antibody-positive sera from 300 patients with various immune-related diseases and 64 anti-nuclear antibody-negative sera were analysed for binding to S1-nuclease-treated double stranded (ds) DNA. In addition, the pattern of reactivity of 50 selected anti-dsDNA-positive sera was established using denatured (d) DNA and poly[dA-dT] X poly[dA-dT] double-stranded alternating copolymer (dAT) as additional DNA antigens. None of the 64 anti-nuclear antibody-negative sera and 76 of the 300 anti-nuclear antibody-positive sera (25%) were anti-dsDNA-positive. Of the anti-nuclear antibody-positive and anti-dsDNA-positive sera, 48 (63%) were from systemic lupus erythematosus patients, and 7 (9%) from rheumatoid arthritis patients, whereas 21 patients (27.6%) suffered from various immune and non-immune related diseases. Anti-dsDNA-positive reactivity was highly correlated with dDNA and dAT reactivity (r = 0.906, p < 0.0001 and r = 0.93, p < 0.0001, respectively). Although the majority of the 50 selected (37 systemic lupus erythematosus and 13 non-systemic lupus erythematosus) anti-dsDNA-positive sera concomitantly bound to both additional antigens, 7 of these (14%) did not bind to dAT, and 2 (4%) did not bind to dDNA. Anti-dsDNA-positive sera (n = 37) showed a similar pattern, in which 8.1% and 2.7% of sera did not bind to dAT and to dDNA, respectively. In contrast, anti-dsDNA-negative sera from various immune-related diseases bound either ssDNA (12.5%) or dDNA and dAT (12.5%). These data suggest that dsDNA and dAT-based assays detect similar but not identical specificities in the sera of patients suffering from systemic lupus erythematosus and in a proportion of non-systemic lupus erythematosus patients.

T cell subset composition in remission phase of systemic connective tissue diseases.

The proportions and numbers of peripheral blood mononuclear cells bearing T-cell markers (CD3/HLA-DR, CD4/CD29, CD4/CD45, CD8/CD56) were analyzed using two-color flow cytometric analysis in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SS) in the remission phase of the diseases. The number of T cells (CD3+) in the blood was significantly decreased in SLE patients only; in these patients, but also in RA patients, an increased number of activated T cells (CD3+ HLA-DR+) was found. The number and proportion of helper T cells (CD4+) were decreased in SLE and SS, and normal in RA patients. In contrast, helper-inducer (CD4+ CD29+) and suppression-inducer (CD4+ CD45+) cells were both significantly increased in RA patients, decreased in SLE (only CD4+ CD45+ significantly) and unchanged in SS patients. Interestingly, however, the proportions of helper-inducer cells relative to total helper (CD4+) cell pool were significantly increased in all three groups of patients, whereas the proportion of suppression-inducer (CD4+ CD45+) cells was significantly decreased, but in SLE patients only. It is thus possible that this parameter is most pertinent to the disease status in the model studied. The population of CD8+ cells appeared more abundant in SLE patients, and the pool of CD8+ CD56+ cell was significantly enlarged in RA patients. It appears that the remission phase of disease in RA, SLE and SS patients still contains a substantial activation of the immune system, but the respective mechanisms are quite different in RA patients on one side, and SLE and SS patients on the other side.(ABSTRACT TRUNCATED AT 250 WORDS)