Association of Variants in PPARγ2, IGF2BP2, and KCNQ1 with a Susceptibility to Gestational Diabetes Mellitus in a Korean Population

Purpose

Patients with gestational diabetes mellitus (GDM) have been reported to exhibit the same genetic susceptibility as that observed in those with type 2 diabetes mellitus (T2DM). Recent polymorphism studies have shown that several genes are related to T2DM and GDM. The aim of this study was to examine whether certain candidate genes, previously shown to be associated with T2DM, also offer a specific genetic predisposition to GDM.

Materials and Methods

The current study was conducted in 136 Korean pregnant women, who gave birth at Gil Hospital, from October 2008 to May 2011. These study subjects included 95 subjects with GDM and 41 non-diabetic controls. We selected the specific genes of PPARγ², IGF2BP2, and KCNQ1 for study and amplified them using the polymerase chain reaction. This was followed by genotyping for single nucleotide polymorphisms. We then compared the genotype frequencies between patients with GDM and non-diabetic controls using the χ² test. We obtained and analyzed clinical information using Student''s t-test, and statistical analyses were conducted using logistic regression with SPSS Statistics software, version 19.0.

Results

Significant differences were observed in maternal age, body mass index, weight gain and weight at time of delivery between the groups compared. Among pregnant women, polymorphisms in PPARγ² and IGF2BP2 were shown to be highly correlated with GDM occurrence, whereas no correlation was found for KCNQ1 polymorphisms.

Conclusion

Our results indicated that genetic polymorphisms could also be of value in predicting the occurrence and diagnosis of GDM.     

Is there a relation between vitamin D,interleukin-17, and bone mineral density in patients with inflammatory bowel disease?

IntroductionIn inflammatory bowel diseases (IBD), osteopenia and osteoporosis constitute a significant medical problem. Cytokines, especially IL-17, play an important role in the pathogenesis of IBD and osteoporosis. Vitamin D is a regulator of bone metabolism, and helps maintain immune system homeostasis.Material and methodsThe research sample consisted of 208 persons: 83 patients (age 35 ±11.99 years) with Crohn’s disease (CD); 86 patients (age 39.58 ±14.74 years) with ulcerative colitis (UC); and 39 persons (age 30.74 ±8.63 years) in the control group (CG). Clinical data on bone mineral density of the lumbar spine (L2-L4), bone mineral density of the femoral neck (FN), and body mass index (BMI) were collected. 25OHD and IL-17 serum concentrations were also measured.ResultsBody mass index (kg/m²) results: in CD, 21.51 ±3.68; in UC, 23.31 ±4.38; and in CG, 24.57 ±3.45 (p < 0.01). Densitometry results for L2–L4 T-score SD: in CD –0.83 ±1.45; in UC –0.47 ±1.15; in CG 0.09 ±0.70. Densitometry results for FN T-score SD: in CD –0.62 ±1.26; in UC –0.29±1.17; in CG 0.41 ±1.03 25OHD (ng/ml) serum concentrations: in CD, 21.33±12.50; in UC, 22.04±9.56; in CG, 21.56±9.11 (ns). IL-17 (pg/ml) serum concentrations: in CD, 8.55±10.99; in UC, 11.67±12.97; in CG, 5.16±9.11 (ns).ConclusionsInflammatory bowel diseases patients and persons from the CG did not differ in vitamin D or IL-17 levels. Patients with a mild course of the disease had a higher vitamin D concentration and bone mineral density. In UC, higher vitamin D concentrations were associated with lower IL-17 concentrations. The IBD patients with a severe course of the disease had a lower body mass than those in the CG and the patients with a mild course of the disease.     

Early administration of tocilizumab in hospitalized COVID-19 patients with elevated inflammatory markers; COVIDSTORM—a prospective,randomized, single-centre,open-label study

ObjectivesSevere COVID-19 is associated with an imbalanced immune response. We hypothesized that patients with enhanced inflammation, as demonstrated by increased levels of certain inflammatory biomarkers, would benefit from interleukin-6 blockage.MethodsPatients hospitalized with COVID-19, hypoxemia, and at least two of four markedly elevated markers of inflammation (interleukin-6, C-reactive protein, ferritin, and/or D-dimer) were randomized for tocilizumab (TCZ) plus standard of care (SoC) or SoC alone. The primary endpoint was clinical status at day 28 assessed using a seven-category ordinal scale, and the secondary endpoints included intensive care unit admission, respiratory support, and duration of hospital admission.ResultsClinical status at day 28 was significantly better in patients who received TCZ in addition to SoC compared with those who received SoC alone (p = 0.037). By then, 93% of patients who received TCZ (n = 53 of 57) and 86% of control patients (n = 25 of 29) had been discharged from the hospital. In addition, 47% of TCZ patients (n = 27 of 57) and 24% of control patients (n = 7 of 29) had resumed normal daily activities. The median length of hospitalization was 9 days (interquartile range, 7–12) in the TCZ group and 12 days (interquartile range, 9–15) in the control group (p = 0.014).DiscussionIn patients hospitalized with COVID-19, hypoxemia, and elevated inflammation markers, administration of TCZ in addition to SoC was associated with significantly better clinical recovery by day 28 and a shorter hospitalization compared with SoC alone.     

New mutations, hotspots, and founder effects in Brazilian patients with steroid 5α-reductase deficiency type 2

Mutations of the steroid 5-reductase type 2 (SRD5A2) gene in 46,XY subjects cause masculinization defects of varying degrees, due to reduced or impaired enzymatic activity. In this study, sequence abnormalities of the SRD5A2 gene were assessed by polymerase chain reaction with specific primers and automated sequencing analysis in DNA samples from 20 patients with suspected steroid 5-reductase type 2 deficiency from 18 Brazilian families. Eleven subjects presented SRD5A2 homozygous single-base mutations (two first cousins and four unrelated patients with G183S, two with R246W, one with del642T, one with G196S, and one with 217_218insC plus the A49T variant in heterozygosis), whereas four were compound heterozygotes (one with Q126R/IVS3+1G>A, one with Q126R/del418T, and two brothers with Q126R/G158R). Three patients were heterozygous for A207D, G196S, and R266W substitutions. The V89L polymorphism was found in heterozygosis in one of them (with A207D) and in one case with an otherwise normal gene sequence. The A49T variant was also detected in heterozygosis in the second case without other sequencing abnormalities. Four patients harbor yet non-described SRD5A2 gene mutations: a single nucleotide deletion (del642T), a G158R amino acid substitution, a splice junction mutation (IVS3+1G>A), and the insertion of a cytosine (217_218insC) occurring at a CCCC motif. This is the first report of a single-nucleotide insertion in the coding sequence of the SRD5A2 gene. In addition to these new mutations, this investigation reveals the prevalence of G183S substitution among a subset of African–Brazilian patients and presents evidences of the recurrence of already known mutations.     

Abnormal glycosylation of α2-macroglobulin,a non-acute-phase protein,in patients with autoimmune diseases

Previous studies from this and other laboratories have shown that abnormal glycosylation of several acute-phase proteins can be detected in various pathological conditions including autoimmune diseases. In the present study, we have investigated if abnormal glycosylation is limited to acute-phase proteins. We used the concanavalin A (Con A) blots in conjunction with the peptide mapping techniques to analyze serum samples and cerebrospinal fluids (CSF) obtained from patients with autoimmune diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), mixed connective tissue disease (MCTD), scleroderma (SCL), Sjögren's syndrome (SS), and polymyositis (PM); diseases of probable autoimmune origin: hepatopathies (HP); diseases of suspected autoimmune origin: schizophrenia and Alzheimer's disease (AZ); and conditions not related to autoimmunity: pregnancy (PG) and elevation of the carcinoembryonic antigen (CEA), in comparison to normal donors (NHS). We have micropurified two human proteins; ₂-macroglobulin, a non-acute-phase protein, and-chain of haptoglobin, a known acute-phase protein, from serum samples of individual patients with SLE, RA, MCTD, SCL and SS, and from PG and NHS for analysis. The identity of the purified proteins was confirmed by immunoblots using either monospecific polyclonal or monoclonal antibodies, and by directN-terminal amino acid sequencing. Peptide maps for each of these proteins were generated usingStaphylococcus aureus protease V₈, a Glu-C endopeptidase. When the peptide fragments of ₂-macroglobulin were resolved by SDS-PAGE and visualized using silver staining, no differences were noted between patient samples and controls. However, when they were examined by lectin blots using Con A, the Con A-reactive fragments increased specifically and significantly in samples derived from patients of SLE, SCL, MCTD, and RA. Similarly when the peptide fragments of the-chain of haptoglobin were visualized by silver staining, no differences were noted; however, the Con A reactivity of specific fragments increased in SLE, RA, SCL, and SS patients. Analysis of these results indicated that there has been a selective increase in Con A-reactive fragments in both acute-phase and non-acute-phase proteins in autoimmune conditions. Thus, the study of changes in glycosylation patterns in selected serum proteins may be a valuable diagnostic approach to define the pathophysiology of inflammatory and autoimmune disorders.     

Clinical characteristics and treatment outcomes of pulmonary invasive fungal infection among adult patients with hematological malignancy in a medical centre in Taiwan, 2008–2013

Background/purposeThis study was aimed to investigate clinical characteristics and treatment outcomes of pulmonary invasive fungal infection (IFI) among patients with hematological malignancy.MethodsAll patients with hematological malignancy who were treated at a medical centre from 2008 to 2013 were evaluated. Pulmonary IFI was classified according to the European Organization for Research and Treatment of Cancer 2008 consensus.ResultsDuring the study period, 236 (11.3%) of 2083 patients with hematological malignancy were diagnosed as pulmonary IFI, including 41 (17.4%) proven, 75 (31.8%) probable, and 120 (50.8%) possible cases. Among the 116 patients of proven and probable cases of pulmonary IFI, aspergillosis alone (n = 90, 77.6%) was predominant, followed by cryptococcosis alone (n = 9, 7.8%), and mucormycosis (n = 4, 3.4%). The overall incidence of patients with pulmonary IFI was 5.9 per 100 patient-years. The highest incidence (per 100 patient-year) was found in patients with acute myeloid leukaemia (13.7) followed by acute lymphoblastic leukaemia (11.3), and myelodysplastic syndrome/severe aplastic anaemia (6.7). Fourteen (5.9%) of the 236 patients with pulmonary IFI died within 12 weeks after diagnosis of pulmonary IFI. Univariate analysis revealed that elderly age (>65 years) (P = 0.034), lack of response to anti-fungal treatment (P < 0.001), and admission to the intensive care unit (ICU) (P < 0.001) were predictors of poor prognosis. However, only admission to the ICU was an independent predictor of poor prognosis for 12-week mortality (P = 0.022) based on multivariate analysis.ConclusionPatients with acute leukaemia and myelodysplastic syndrome/severe aplastic anaemia were at high risk of pulmonary IFI.     

Procalcitonin and macrophage inflammatory protein-1 beta (MIP-1β) in serum and peritoneal fluid of patients with decompensated cirrhosis and spontaneous bacterial peritonitis

PurposeSpontaneous bacterial peritonitis (SBP) is the most frequent infection in patients with cirrhosis causing significant mortality which requires rapid recognition for effective antibiotic therapy, whereas ascitic fluid cultures are frequently negative. The aim of this study was to evaluate the SBP diagnostic efficacy of procalcitonin (PCT) and macrophage inflammatory protein-1 beta (MIP-1β) measured in serum and peritoneal fluid.Material/methodsThirty-two participants with liver cirrhosis and ascites were included into the study (11 females and 21 males, mean age 49.5 ± 11.9 years). The peritoneal fluid and venous blood were collected for routine laboratory examinations and measurements of PCT and MIP-1β. Patients were divided into two groups according to the ascitic absolute polymorphonuclear leukocytes count (≥250 mm⁻³ and <250 mm^–3).ResultsAscites was sterile in 22 participants and SBP was diagnosed in 10 patients. Serum and ascitic levels of PCT and MIP-1β did not correlate with clinical and routine laboratory parameters. MIP-1β in the ascitic fluid was significantly higher in patients with SBP (213 ± 279 pg/ml vs. 66.3 ± 49.8 pg/ml; p = 0.01). The sensitivity and specificity for diagnosis of SBP with ascitic MIP-1β were 80% and 72.7%, respectively (cut-off value 69.4 pg/ml) with AUROC 0.77 (95%CI 0.58–0.96). Serum levels of MIP-1β showed lower diagnostic yield. Serum and ascitic PCT levels were not different in patients with and without SBP.ConclusionsMIP-1β concentration in ascitic fluid may distinguish patients with and without SBP with satisfactory sensitivity and specificity. Chemokines should be further explored for diagnostic use.     

Safety and efficacy of low-dose PI3K inhibitor taselisib in adult patients with CLOVES and Klippel–Trenaunay syndrome (KTS): the TOTEM trial,a phase 1/2 multicenter,open-label,single-arm study

PurposePIK3CA pathogenic variants in the PIK3CA-related overgrowth spectrum (PROS) activate phosphoinositide 3-kinase signaling, providing a rationale for targeted therapy, but no drug has proven efficacy and safety in this population. Our aim was to establish the six-month tolerability and efficacy of low-dose taselisib, a selective class I PI3K inhibitor, in PROS patients.MethodsPatients over 16 years with PROS and PIK3CA pathogenic variants were included in a phase IB/IIA multicenter, open-label single-arm trial (six patients at 1 mg/day of taselisib, then 24 at 2 mg/day). The primary outcome was the occurrence of dose limiting toxicity (DLT). Efficacy outcomes were the relative changes after treatment of (1) tissue volume at affected and unaffected sites, both clinically and on imaging; (2) cutaneous vascular outcomes when relevant; (3) biologic parameters; (4) quality of life; and (5) patient-reported outcomes.ResultsAmong 19 enrolled patients, 2 experienced a DLT (enteritis and pachymeningitis) leading to early trial termination (17 treated, 10 completed the study). No serious adverse reaction occurred in the 1 mg cohort (n = 6). No significant reduction in affected tissue volume was observed (mean −4.2%; p = 0.81; SD 14.01). Thirteen (76.4%) participants reported clinical improvement (pain reduction, chronic bleeding resolution, functional improvement).ConclusionDespite functional improvement, the safety profile of low-dose taselisib precludes its long-term use.     

Interaction of MT1-MMP and laminin-5γ2 chain correlates with metastasis and invasiveness in human esophageal squamous cell carcinoma

To gain insights into metastatic mechanisms in esophageal squamous cell carcinoma (ESCC), we established sublines (MLuB1 and MLuC1) with different capacity of spontaneous lung metastasis by subcutaneous injection of a human ESCC cell line (EC 9706) into nude mices. The incidence of the mice with lung metastasis produced by MLuC1 (87%) was significantly higher than that of MLuB1 (22%). The gene expression profiles of the two sublines were compared with cDNA arrays containing 5,000 known genes, and 47 genes were differentially expressed ≥2.0 fold. Laminin-5γ2 chain (Ln-5γ2) was one of the up-regulated genes in MLuC1 cells. Proteolytically processed forms of γ2 are known to promote migration of a multitude of epithelial cells in vitro. Western-blotting analysis revealed that degraded fragments of Ln-5γ2 and active form of membrane-type matrix metalloproteinase-1 (MT1-MMP) in MLuC1 was significantly higher than those in MLuB1. Expression of MT1-MMP was observed in 60 of 75 Ln-5γ2-positive carcinoma tissues (80%). Co-expression of the two proteins was significantly associated with depth of invasion (P = 0.012). Moreover, proteolytic fragments of Ln-5γ2 and active forms of MT1-MMP were frequently found in tumor tissues, whereas in the corresponding normal esophageal tissues there were only intact forms of γ2 and MT1-MMP. siRNA-mediated silencing of MT1-MMP significantly reduced production of γ2′ and γ2x in MLuC1 cells and inhibited cell migration. The results suggest that MT1-MMP is an enzyme responsible for Ln-5γ2 cleavage in ESCC, and interaction between them may play a critical role in promoting invasion and metastasis of human ESCC. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Endogenous antibody responses to mucin 1 in a large multiethnic cohort of patients with breast cancer and healthy controls: Role of immunoglobulin and Fcγ receptor genes

High levels of naturally occurring IgG antibodies to mucin 1 (MUC1), a membrane-bound glycoprotein that is overexpressed in patients with breast cancer, are associated with good prognosis. This suggests that endogenous anti-MUC1 antibodies have a protective effect and, through antibody-mediated host immunosurveillance mechanisms, might contribute to a cancer-free state. To test this possibility, we characterized a large number of multiethnic patients with breast cancer and matched controls for IgG antibodies to MUC1. We also aimed to determine whether the magnitude of anti-MUC1 antibody responsiveness was associated with particular immunoglobulin GM (γ marker), KM (κ marker), and Fcγ receptors (FcγR) genotypes. After adjusting for the confounding variables in a multivariate analysis, we found no significant difference in the levels of anti-MUC1 IgG antibodies between patients and cancer-free controls. However, in patients and controls, particular GM, KM, and FcγR genotypes—individually or epistatically—were significantly associated with the levels of anti-MUC1 IgG antibodies in a racially restricted manner. These findings, if confirmed in an independent investigation, could help identify individuals most likely to benefit from a MUC1-based therapeutic or prophylactic vaccine for MUC1-overexpressing malignancies.     

Stem cell-related proteins C-KIT, C-MYC and BMI-1 in juvenile nasopharyngeal angiofibroma--do they have a role?

Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascular tumour, occuring almost exclusively in adolescent males. Histogenesis of JNA remains unclear, two optional theories proposing either fibrous or vascular tissue as the tissue of origin. Stem cell-related proteins have been discussed to possibly participate in the growth of these tumours. In our study, we reviewed retrospective clinicopathological data of 26 JNA patients. By immunohistochemistry, we investigated the cellular distribution and expression levels of stem cell-related proteins C-KIT, C-MYC and BMI-1 and their correlation with cell and vessel density of the tumour. Contrary to earlier reports, we detected C-KIT expression in addition to stromal cells also in endothelial cells. The C-KIT expression was more dominant in slit vessels than large vessels. A significant correlation was found between endothelial immunoexpression of C-KIT and cellular density of the tumour. C-MYC and BMI-1 expression was detected in stromal cells only. Due to our finding of C-KIT expression in both stromal and endothelial cells and the strong correlation between the endothelial C-KIT expression and cellular density, we suggest that, besides the stromal tissue, the vascular component might take part in the neoplastic growth of JNA.     

ncreased interleukin 33 in patients with neuro-Behcet＇s isease,correlation with MCP- 1 and IP- 10 chemokines

Neurological involvement in Behcet＇s disease （BD）, namely, neuro-Behcet＇s disease （NBD）, causes devastating central ner- vous system （CNS） complications and is present in 5% to 30% of patients with BD.1 Immunological and molecular pathways are involved in NBD and include the release ofinterleukin （IL）- 1, -6 and -8, and TNF-α and IFN-γ into cerebrospinal fluid （CSF）,2 which reflects a nonspecific inflammatory pattern that is comnatihle with anta-inflammatnry disease pathways.     

Polymorphisms of glutathione S-transferase M1, T1 and P1 in patients with reflux esophagitis and Barrett’s esophagus

Reflux esophagitis (RE) and Barrett’s esophagus (BE) belong to the most common esophageal complications of gastroesophageal reflux disease. Glutathione S-transferase (GST) enzymes play an important role in cellular protection against oxidative stress and toxic foreign chemicals. Therefore, we investigated the hypothesis that polymorphisms in genes for these detoxifying enzymes could influence susceptibility to RE and BE. GSTM1, GSTT1 and GSTP1 loci were analyzed by PCR-based methods in 64 patients with RE (and an additional group of 22 subjects with BE as the fourth grade of esophagitis) and 173 unrelated controls. There were no significant differences in the distributions of GSTM1 and GSTT1 genotypes between the controls and patients with RE or BE. Similarly, frequencies of GSTP1 alleles were non-significantly different between the control and RE groups. However, GSTP1 B allele carriers were more frequent among the patients with BE compared to those in the reflux esophagitis group (P = 0.04, OR = 2.10, 95% CI 0.99–4.44) and most significantly when compared to the controls (P = 0.0067, P _corr < 0.05, OR = 2.56, 95%CI 1.30–5.05). Although the GSTM1 and GSTT1 genes did not show any relationship with reflux disease, the GSTP1 gene might be one of the risk factors associated with susceptibility to RE, especially to BE.     

Bronchial hyper-responsiveness, subepithelial fibrosis, and transforming growth factor-β1 expression in patients with long-standing and recently diagnosed asthma

Introduction:  Chronic inflammation in asthmatic airways leads to bronchial hyper-responsiveness (BHR) and the development of structural changes. Important features of remodeling include the formation of subepithelial fibrosis due to increased collagen deposition in the reticular basement membrane. Transforming growth factor (TGF)-β might be a central mediator of tissue fibrosis and remodeling. Materials and Methods:  Immunohistochemistry was used to measure collagen III deposition and TGF-β₁ expression in biopsies from patients with long-standing asthma treated with inhaled corticosteroids, patients with recently diagnosed asthma, and control subjects. Computer-assisted image analysis was used to evaluate total basement membrane (TBM) thickness. Results:  Asthmatics, particularly those with long-standing asthma, had thicker TBMs than healthy subjects. Collagen III deposition was comparable in the studied groups. BHR was not correlated with features of mucosal inflammation and was lower in steroid-treated patients with long-standing asthma than in subjects with newly diagnosed asthma untreated with steroids. Epithelial TGF-β₁ expression negatively correlated with collagen III deposition and TBM thickness. Conclusions:  The study showed that TBM thickness, but not collagen III deposition, could be a differentiating marker of asthmatics of different disease duration and treatment. The lack of correlation between BHR and features of mucosal inflammation suggests the complexity of BHR development. Corticosteroids can reduce BHR in asthmatics, but it seems to be less effective in reducing subepithelial fibrosis. The role of epithelial TGF-β₁ needs to be further investigated since the possibility that it plays a protective and anti-inflammatory role in asthmatic airways cannot be excluded.     

HIV-1 progression links with viral genetic variability and subtype,and patient’s HLA type: analysis of a Nairobi-Kenyan cohort

In a Nairobi-Kenyan cohort of 50 HIV-1 positive patients, we analysed the prevalence of HIV-1 subtypes and human leucocyte antigen (HLA) alleles. From this cohort, 33 patients were selected for the analysis of HIV-1 infection progression markers (i.e. CD4 cell counts and viral loads) and their association with HIV-1 genetic variability and subtype, and patient’s HLA type. HIV-1 gag genetic variability, analysed using bioinformatics tools, showed an inverse relationship with CD4 cell count whereas with viral load that relationship was direct. Certain HLA types and viral subtypes were also found to associate with patients’ viral load. Associations between disease parameters and the genetic makeup of the host and virus may be crucial in determining the outcome of HIV-1 infection.     

The effects of systemic treatment with aminobisphosphonates and statins on circulating Vγ9Vδ2-T cells in patients with advanced cancer

Aminobisphosphonates (NBP) are used for treatment of metastatic bone disease. Frequently, patients undergoing NBP-treatment experience side-effects, known as acute phase response (APR), resulting from cytokine production by Vγ9Vδ2-T cells. As opposed to NBP, statins reduce intracellular phosphoantigen levels and prevent NBP-induced Vγ9Vδ2-T cell activation in vitro. We conducted a pilot study in patients with (bone-)metastasized malignancies receiving NBP-treatment and evaluated the phenotype and function of circulating Vγ9Vδ2-T cells in vivo and the effects of statins on Vγ9Vδ2-T cell responses and the associated APR. We observed reduced expression of perforin, granzyme B and HLA-DR on Vγ9Vδ2-T cells in patients treated with NBP and statins. However, statins could not prevent NBP-induced changes in circulating Vγ9Vδ2-T cell numbers or production of IFNγ and TNFα. Consistent with this, simvastatin could not prevent the occurrence of APR upon NBP-infusion. These observations call for the exploration of alternative strategies to prevent collateral APR upon NBP treatment.     

Serum soluble adhesion molecules (sICAM-1, sVCAM-1, sE-selectin) and neopterin in patients with Sjögren's syndrome

Sj?gren's syndrome is a systemic autoimmune disease characterized by focal lymphocytic infiltration of the salivary and lacrimal glands. Expression and up-regulation of adhesion molecules and activation of cellular immune system is essential for the migration of inflammatory cells into tissues. Soluble forms of adhesion molecules sICAM-1, sVCAM-1, sE-selectin and neopterin were analyzed in serum of 17 patients with primary Sj?gren's syndrome and 11 patients with secondary Sj?gren's syndrome together with 26 age-matched healthy blood donors. There were significantly higher serum concentrations (mean +/- 1SD) of sICAM-1 (362.0 +/- 67.9 ng/ml, p < 0.001), sE-selectin (78.7 +/- 28.1 ng/ml, p < 0.001) and neopterin (17.9 +/- 6.4 nmol/l, p < 0.001) in primary Sj?gren's syndrome patients in comparison to control group (sICAM-1: 128.3 +/- 46.9 ng/ml, sE-selectin: 46.3 +/- 39.5 ng/ml, and neopterin: 7.6 +/- 2.3 nmol/l). Sera from patients with secondary Sj?gren's disease contained significantly higher levels of sICAM-1 (356.0 +/- 62.4 ng/ml, p < 0.001), sE-selectin (65.5 +/- 27.0 ng/ml, p < 0.05), and neopterin (18.8 +/- 9.8 nmol/l, p < 0.001) in comparison with control group. There were no significant differences between patients with primary and secondary Sj?gren's syndrome in any parameters tested. No statistically significant differences in serum levels of sVCAM-1 were found either in patients with primary or secondary SS compared to control group.