Major histocompatibility complex class II (DRB1*, DQA1*, and DQB1*) and DRB1*04 subtypes' associations of Hashimoto's thyroiditis in a Greek population.

Hashimoto's thyroiditis (HT) is an autoimmune disease resulting from complex interactions between genetic and environmental factors. The disease is associated with certain human leukocyte antigen (HLA) class II alleles in various populations. We aimed to determine in this study, for the first time in a Greek population, the association of HLA-DRB1*, -DQA1*, and -DQB1* alleles with HT. HLA-DRB1*, -DQA1*, and -DQB1* alleles' and -DRB1*04 subtypes' distribution was evaluated in 125 patients with HT and in 500 healthy control individuals by using a DNA-based sequence-specific primer method. Chi(_)squared tests and Bonferroni correction method were applied in the statistical analysis of the data. Significantly higher frequency of DRB1*04 (24.8% vs 7.7%, P < 0.0001) was observed in HT patients, while HLA-DRB1*07 was significantly decreased (2.8% vs 7.9%, P < 0.05). HLA-DRB1*04 subtyping showed a significant increase of DRB1*0405 (21% vs 7.8%, P < 0.0001) in HT patients. Also significant high frequencies of DQB1*0201 (14.8% vs 8.2%, P < 0.001), DQB1*0302 (18.8% vs 7.0%, P < 0.0001), and DQA1*0301 (25.6% vs 7.8%, P < 0.0001) were recorded in the patient group. Conducting the first research of this kind in a Greek population, our study tries to provide an evaluation of the prevalence of HT relating to HLA-DRB1*0405, and we report a relative risk of 2.7 for HT in a Greek population.

Relevance of procalcitonin levels in comparison to other markers of inflammation in hemodialysis patients.

PURPOSE: The objective of this study was to evaluate the diagnostic value of serum procalcitonin (PCT) in hemodialysis (HD) patients and its correlation to other traditional inflammatory markers. METHODS: We measured plasma PCT levels in 120 patients on maintenance HD. PCT levels were compared with C-reactive protein (CRP), interleukin-6 (IL-6), prealbumin, and albumin. We also examined the above parameters subgroups, especially in diabetics and the elderly. Relations between parameters were studied by Spearman's correlation. RESULTS: PCT concentrations were higher than the upper normal limit of 0.5 ng/ mL in 38% of the patients. All patients with increased CRP had PCT concentrations higher than the upper normal limit. Plasma CRP concentrations were positively correlated to IL-6 (r = 0.304). Prealbumin was negatively correlated with CRP (r = 0.259) and with IL-6 (r = 0.388). CONCLUSIONS: The combination of elevated IL-6 and CRP levels was associated with an altered nutritional status. The concomitant elevations in PCT, CRP, and IL-6 could be more sensitive in the evaluation of inflammation.

Cellular immunity and levels of parathyroid hormone in uremic patients receiving hemodialysis.

OBJECTIVE: The clinical relevance of altered lymphocyte function and the possible relation with uremic toxins, such as parathyroid hormone (PTH) is not well understood. We studied the changes in cellular immunity in patients in hemodialysis (HD) therapy and examined the relationship between T-lymphocyte function and plasma levels of PTH. PATIENTS AND METHODS: Thirty-four patients (14 male) were enrolled in this study (mean age: 63.20 +/- 10.01 years, M +/- SD, 12 h/week HD). Our study population was divided into two groups: 18 patients with increased levels of PTH and 16 patients with normal levels of PTH. Lymphocyte subsets (CD2+, CD3+, CD3+/4+, CD3+/8+, CD19+, CD3-/16+56+, CD4/CD8 ratio) were quantitated in both groups using monoclonal antibodies (Immunotech, Coulter) and flow cytometric analysis. Following analysis of variance (ANOVA) testing was performed to test differences between groups (SPSS version 10). RESULTS: A significant increase of CD2 was noticed in patients with increased levels of PTH (84.8 +/- 5.5 vs. 79.8 +/- 4, p<0.05). The CD3 population was also increased in patients with elevated PTH (72 +/- 8.6 vs. 68 +/- 9.2, p=NS). This group of patients had also significantly increased levels of CD3/8 (44.8 +/- 9.8 vs. 37.1 +/- 5.8, p<0.05). The CD4/CD8 ratio levels were higher in patients with elevated PTH compared with those who had normal PTH (2.2 +/- 1.5 vs. 1.5 +/- 0.8, p=NS). CONCLUSIONS: The elevated level of PTH seems to affect the lymphocyte function and is associated with changes in cellular immunity in the hemodialysis population. Our study is in progress in order to enlarge our study population and collect more data, which will lead us to more solid conclusions.

Lymphocytes subsets in the course of continuous ambulatory peritoneal dialysis (CAPD).

BACKGROUND: We studied lymphocyte subset counts in comparison with normal subjects in order to clarify the abnormalities of cellular immune responses in uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: The study included 37 CAPD patients and 45 normal individuals, as the control group. For the study, CAPD patients were divided into four groups depending on duration of replacement therapy. Group I consisted of patients treated for 0-6 months (n=6), group II for 6-12 months (n=6), group III for 13-24 months (n=16), and group IV for more than 25 months (n=9). Flow cytometry was used for estimation of lymphocyte subsets (determination of CD2, CD3, CD3+/CD4+, CD3+/CD8+, CD3-/16+56+, CD19, CD4/CD8). RESULTS: Our patients started CAPD with decreased lymphocyte subset counts, slightly above the normal range (excluding CD3 -/16+56+, CD2). After 6 months of CAPD therapy, an increase in CD4/CD8 ratio was observed and all examined lymphocyte subset counts decreased (excluding CD2). In patients on CAPD for more than 25 months, CD3+/CD4+, CD19 counts were below the normal range, CD3 -/16+56+ exceeded the upper limit of normal range and at the same time mean total lymphocyte count (TLC) was maintained in the normal range. CONCLUSIONS: We recommend lymphocyte subset determinations for detection of immune abnormalities in the course of CAPD treatment.

Salivary IgA and serum IgA and IgG antibodies to Candida albicans in HIV-infected subjects.

This study sought to determine IgA, IgG antibodies to Candida albicans in whole saliva and serum from HIV-infected patients and to compare them to a group of healthy controls. The study population consisted of 34 HIV-infected individuals free of any other systemic diseases and thirty healthy controls. IgA concentrations in saliva and IgA and IgG concentrations in serum were measured by a micro enzyme-linked immunosorbent assay. No significant differences were observed in salivary and serum IgA antibodies to C. albicans between the two study groups. Serum IgG antibodies were found to be significantly lower in the HIV-infected (P < 0.05). No significant changes were observed in the specific activity of anti-Candida IgA and IgG antibodies in saliva and serum, in both the study groups. The undifferentiated levels of secretory-IgA antibodies to C. albicans in the patients' and the controls' saliva could be an indicator of the high immune response to opportunistic infections of the HIV-infected subjects, a fact that is verified by the lack of oral candidiasis in the patients' group. The low levels of IgG antibodies in the serum of the HIV-infected patients confirm the high immune response of them.

Interleukin-1 beta and tumor necrosis factor-alpha in normal/infertile men.

Cytokines play an important role in intercellular communications. Human sperm contains a wide spectrum of cytokines. such as interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha). Their effects on semen quality are subject to debate. The aim of this study was to determine concentrations of IL-1beta and TNF-alpha in normal fertile men and in different groups of male infertility in an attempt to clarify the physiology and suggest possible clinical uses. Sixty-six subfertile male patients with varicocele (n = 22). infection of accessory genital glands (n = 14), varicocele plus infection (n = 4), chronic epididymitis (n = 8). post-renal transplantation status (n = 5), idiopathic oligoasthenoteratospermia (n = 9), cryptorchidism (n = 1), and homozygous beta-thalassemia (n = 3) as well as 5 male controls were studied through history, physical examination, spermiograms, plasma basal hormonal levels, and IL-1beta and TNF-alpha levels in seminal fluid. There was no significant statistical difference regarding IL-1beta and TNF-alpha among fertile men and subfertile patients of any cause. 1L-1beta and TNF-alpha were in tight positive correlation (p<.001). Determination of IL-1beta and TNF-alpha does not provide useful information in male routine infertility workup. Nevertheless, a better understanding of these mediators in semen of normal men and infertile patients may contribute to a new approach to the management of male infertility.

Can HLA typing predict the outcome of grass pollen immunotherapy?

OBJECTIVE: The aim of this study was to investigate the relationship between HLA molecules and the positive or negative response of atopic patients to specific immunotherapy (SIT). METHODS: We studied 42 atopic multisensitive patients undergoing grass pollen immunotherapy, 42 parents of patients (30 mothers and 12 fathers) and 173 control individuals. HLA class I and class II antigens were typed by a microlymphocytotoxicity test. The typing of DRB1* alleles for atopic patients and their parents was based on the reverse hybridization principle, while for the control group, DNA-RFLP and PCR-SSP methods were used. RESULTS: The frequency of B14 and DRB1*1101-4 antigens/alleles, as well as the A2B5DR11 haplotype, showed a statistically significant difference in those patients who responded to immunotherapy. On the other hand, HLA-A28, B8 and DRB1*0301 antigens/alleles, as well as the frequency of the A1B8 and A1B8DR3 haplotypes, were found to be significantly higher in patients who responded poorly to SIT. DISCUSSION: Our findings support the hypothesis that treatment responsiveness may show an association to HLA molecules, which could thus play a role in the immunological selection and monitoring of atopic patient candidacy for SIT.

Salivary alterations in insulin-dependent diabetes mellitus.

OBJECTIVES: To examine the flow rate and composition of unstimulated whole saliva and of serum in children with newly diagnosed insulin-dependent diabetes mellitus (IDDM) and to compare these with values for a group of healthy controls. DESIGN: Cross-sectional. SETTING: Diabetic Department of a University Hospital in Thessaloniki, Greece. SUBJECTS AND METHODS: The test group was made up of 10 recently diagnosed child patients with IDDM, aged 4-15 years and free of other systemic disease. Ten healthy children aged 5-17 years served as controls. Children were clinically examined before unstimulated saliva was collected over a 5 minute period and blood samples taken. Saliva and serum measurements included glucose, total proteins, albumin and immunoglobulins (IgA, IgG). RESULTS: No significant difference was seen in salivary flow rate between the two groups. Significantly greater concentrations of glucose were seen in saliva and serum in children with IDDM. Neither total protein nor albumin differed significantly between the two groups. Salivary IgA concentration was higher in the test group as was serum IgG. CONCLUSIONS: Findings in this sample suggest that changes in salivary composition may, together with estimated glucose levels, play a helpful diagnostic role in the early stages of IDDM in some children.

Cytokines in the human ovary: presence in follicular fluid and correlation with leukotriene B4.

PURPOSE: This study was undertaken to correlate the follicular levels of interleukin (IL)-1 alpha, IL-2, tumor necrosis factor-alpha (TNF-alpha), and leukotriene (LT) B4 with oocyte maturity, fertilization, and achievement of pregnancy. METHODS: The material was obtained from 22 women undergoing IVF, 8 of whom became pregnant and 14 of whom did not. RESULTS: All of the studied cytokines and LT B4 were found in follicular fluids, but there were no significant differences according to oocyte maturity, fertilization, embryo quality, and achievement of pregnancy. On the other hand, a significant positive correlation was found between IL-1 alpha and TNF-alpha, IL-1 alpha, and LT B4 as well as between TNF-alpha and LT B4 in follicular fluids with subsequently fertilized oocytes. CONCLUSIONS: It seems that IL-1 alpha, TNF-alpha and LT B4 may take part in the process of follicle wall degradation, and their follicular correlations may suggest more optimal follicular and oocyte development and maturation.

Haplotypes of human leukocyte antigens among patients with nasopharyngeal cancer in Greece.

The concept that the major histocompatibility complex (MHC) plays an important role in the pathogenesis of nasopharyngeal cancer (NPC) in several ethnic groups has gained increased attention during the last 15 years. Earlier studies have suggested that an increased risk of NPC is associated with specific phenotypes of human leukocyte antigens (HLA). The present study was performed to examine the association of HLA specificities and haplotypes with NPC in a Greek population. In a genotypical study of 53 patients, a significant association between the haplotype HLA-B5DR11 and NPC was found, mainly in patients > 45 years. Also, the above haplotype was significantly associated with longer disease-free interval. HLA-B5 and HLA-B5DR11 were more often seen among patients with squamous cell histology than among those with the undifferentiated type. These results suggest that MHC loci are probably implicated in the pathogenesis and outcome of NPC in Greek patients.