Attention to Eye Contact in the West and East: Autonomic Responses and Evaluative Ratings

Eye contact has a fundamental role in human social interaction. The special appearance of the human eye (i.e., white sclera contrasted with a coloured iris) implies the importance of detecting another person''s face through eye contact. Empirical studies have demonstrated that faces making eye contact are detected quickly and processed preferentially (i.e., the eye contact effect). Such sensitivity to eye contact seems to be innate and universal among humans; however, several studies suggest that cultural norms affect eye contact behaviours. For example, Japanese individuals exhibit less eye contact than do individuals from Western European or North American cultures. However, how culture modulates eye contact behaviour is unclear. The present study investigated cultural differences in autonomic correlates of attentional orienting (i.e., heart rate) and looking time. Additionally, we examined evaluative ratings of eye contact with another real person, displaying an emotionally neutral expression, between participants from Western European (Finnish) and East Asian (Japanese) cultures. Our results showed that eye contact elicited stronger heart rate deceleration responses (i.e., attentional orienting), shorter looking times, and higher ratings of subjective feelings of arousal as compared to averted gaze in both cultures. Instead, cultural differences in the eye contact effect were observed in various evaluative responses regarding the stimulus faces (e.g., facial emotion, approachability etc.). The rating results suggest that individuals from an East Asian culture perceive another''s face as being angrier, unapproachable, and unpleasant when making eye contact as compared to individuals from a Western European culture. The rating results also revealed that gaze direction (direct vs. averted) could influence perceptions about another person''s facial affect and disposition. These results suggest that cultural differences in eye contact behaviour emerge from differential display rules and cultural norms, as opposed to culture affecting eye contact behaviour directly at the physiological level.     

Seropositivity to Helicobacter pylori heat shock protein 60 is strongly associated with intensity of chronic inflammation, particularly in antrum mucosa: an extension of an 18-year follow-up study of chronic gastritis in Saaremaa, Estonia

Helicobacter pylori is a cause of chronic gastritis and leads to development of atrophy in some cases. There is evidence that the heat shock protein 60 (HSP60) of H. pylori is involved in induction of chronic inflammation. Seroprevalence of IgG antibodies to H. pylori HSP60 in an adult cohort from Saaremaa, Estonia (68 persons, median age 57 years), with a high prevalence of antibodies to cell surface proteins of H. pylori (92%) and a well characterized dynamics of chronic gastritis in an 18-year follow-up study, was tested using purified H. pylori HSP60 at a concentration of 1 microg ml(-1) with ELISA. The state of the gastric mucosa and the presence of H. pylori in histological sections in the samples of 1979 and 1997 were assessed in accordance with the Sydney system. Seropositivity for H. pylori HSP60 was 65%. Immunological response to H. pylori HSP60 is associated with the morphological presence of H. pylori in the antrum and corpus (P=0.01) and is strongly correlated with the grade of chronic inflammation, particularly in the antrum mucosa (r=0.34; P=0.003; OR=5.97 (95% CI 1.21-29.3)), but is not associated with development of atrophy during 18 years of follow-up, or with the activity of gastritis. This finding supports the evidence that immunological response to H. pylori HSP60 may play a role in triggering of the inflammatory process in the gastric mucosa.     

Increased Blood Levels of Growth Factors,Proinflammatory Cytokines,and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes

The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th₁) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th₁₇ pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th₁₇ cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.     

Autoantibodies from patients with celiac disease inhibit transglutaminase 2 binding to heparin/heparan sulfate and interfere with intestinal epithelial cell adhesion

Autoantibodies from patients with celiac disease (CD) can influence transglutaminase 2 (TG2) activity and its cellular functions, but the exact mechanisms have remained unknown. Our objective was to study whether autoantibodies could modulate TG2 binding to heparin/heparan sulfate (HS) and intestinal epithelial cell attachment to fibronectin-TG2 matrix. Anti-TG2 antibodies were purified by TG2 affinity chromatography from sera of patients with active CD. Serum and antibody effects on TG2 binding to heparin/HS, on transamidase activity of TG2, as well as on Caco-2 cell attachment to fibronectin-TG2 matrix were assessed using microplate assays. Both sera and purified anti-TG2 antibodies from CD patients with high anti-TG2 IgA levels reduced TG2 binding to heparin/HS as compared with those with low anti-TG2 IgA or controls. There was a negative correlation between anti-TG2 IgA levels and TG2 binding to heparin/HS. Treatment of fibronectin-TG2 coated wells with CD patients' sera or purified anti-TG2 antibodies reduced attachment of Caco-2 cells onto the plate as compared with the control samples. The effect of CD patients' antibodies on Caco-2 cell attachment to fibronectin-TG2 matrix occurred independently of the inhibition of cell adhesion by Arg-Gly-Asp sequence containing peptides. Anti-TG2 autoantibodies had no effect on transamidase activity of TG2 in vitro. We suggest that modulation of adhesion function of TG2 by autoantibodies from patients with CD could be related to the inhibition of TG2 binding to HS residues of cell surface proteoglycans and could have possible implications for CD pathogenesis.     

Association of Helicobacter pylori and gastric autoimmunity: A population-based study

Abstract Based on clinical studies, a negative association between Helicobacter pylori and autoimmune corpus gastritis is described. In the present investigation of an unselected population of 1461 adults we can state, however, that there exists a relationship between H. pylori infection and the development of gastric corpus autoimmunity. As confirmation for the gastric autoantibody development through molecular mimicry, a high homology (72% in 25 amino acid overlap) between the beta subunit of H. pylori urease and that of H + K + ATPase, the gastric parietal cell autoantigen, was revealed.     

LADA and T1D in Estonian population - two different genetic risk profiles

Aims/hypothesis

The aim of our study was to analyze combined impact of 17 polymorphisms at 8 gene regions previously shown to be associated with autoimmunity in diabetes. We hypothesized that the genetic predisposition is multiplicative and joint risk of different diabetic phenotypes forms by distinct combination of susceptibility loci.

Methods

An ethnically homogenous population of Estonian origin, including 65 LADA patients, 154 patients with T1D, 260 patients with T2D and 229 non-diabetic controls, was genotyped for polymorphisms/haplotypes in HLA-DQB1, insulin gene (rs689, rs3842729), PHTF1–PTPN22 region (rs2476601, rs6679677), CTLA4 region (rs231806, rs16840252, rs5742909, rs231775, rs3087243, rs2033171), ICOS region (rs10932037, rs4675379), CD25 (rs706778), CD226(rs763361), NAA25 (rs17696736).

Results

As expected, the risk of T1D was consistently attributed by HLA-DQB1 haplotypes, but also by haplotypes of INS and PHTF1–PTPN22 region, and rs17696736 in NAA25. By contrast, LADA was associated only with T1D-protective HLA haplotypes and with two more frequent haplotypes of the CTLA4. It is of interest, that seldom CT haplotype of PHTF1–PTPN22 region carried the risk for autoantibody-negative T2D. The final best-fitted model for T1D genetic risk contained six gene regions (HLA-DQB1, INS, PHTF1, CTLA4 + 49, CD226 and NAA25) and for LADA only two (HLA-DQB1 and CTLA4 + 49). The AUCs of these models are 0.869 and 0.693, respectively.

Conclusions

Classical T1D-risk haplotypes of HLA and some non-HLA loci describe quite well the genetic risk for T1D but not for LADA. The need of further studies should be stressed to discover the real risk factors for slower forms of autoimmune diabetes in adults.     

Kinetic and functional characterisation of the heparin‐binding peptides from human transglutaminase 2

Transglutaminase 2 (TG2) is an autoantigen in celiac disease (CD) and it has multiple biologic functions including involvement in cell adhesion through interactions with integrins, fibronectin (FN), and heparan sulfate proteoglycans. We aimed to delineate the heparin‐binding regions of human TG2 by studying binding kinetics of the predicted heparin‐binding peptides using surface plasmon resonance method. In addition, we characterized immunogenicity of the TG2 peptides and their effect on cell adhesion. The high‐affinity binding of human TG2 to the immobilized heparin was observed, and two TG2 peptides, P1 (amino acids 202–215) and P2 (261–274), were found to bind heparin. The amino acid sequences corresponding to the heparin‐binding peptides were located close to each other on the surface of the TG2 molecule as part of the α‐helical structures. The heparin‐binding peptides displayed increased immunoreactivity against serum IgA of CD patients compared with other TG2 peptides. The cell adhesion reducing effect of the peptide P2 was revealed in Caco‐2 intestinal epithelial cell attachment to the FN and FN‐TG2 coated surfaces. We propose that TG2 amino acid sequences 202–215 and 261–274 could be involved in binding of TG2 to cell surface heparan sulfates. High immunoreactivity of the corresponding heparin‐binding peptides of TG2 with CD patient's IgA supports the previously described role of anti‐TG2 autoantibodies interfering with this interaction. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.     

IgG from patients with liver diseases inhibit mitochondrial respiration in permeabilized oxidative muscle cells: Impaired function of intracellular energetic units?

The effect of IgG purified from the sera of healthy persons and patients with primary biliary cirrhosis (PBC) and chronic hepatitis (CH) on ADP dependent respiration (oxidative phosphorylation) in skinned muscle fibers from rat oxidative muscles (heart and M. soleus) and glycolytic skeletal muscle (M. gastrocnemius) was studied. The results show that IgG from three different sources inhibited the rate of respiration by 13, 44 and 42%, respectively, these effects being equally expressed in both types of oxidative muscles, whereas no inhibition was observed in glycolytic muscle. The following washout of unbound IgG did not abolish the inhibition of respiration suggesting that the specific interaction of IgG with antigens had taken place. Laser confocal analysis revealed binding of IgG predominantly to the sarcomeric structures such as Z-disk and M-lines in the cardiomyocytes. The staining of IgG within Z-disks and intermitochondrial space coincided throughout the muscle cells so that transversally serial spaces, each containing mitochondria and adjacent sarcomere, became clearly visible. When the IgG from a CH patient was incubated with the skinned myocardial fibers of the desmin knockout mice, its binding to Z-disks and the sarcomeric area was found to be similar to that in normal cardiac muscle. However, the transversal staining pattern was disintegrated, because of the slippage of the myofibrils in relation to each other and accumulation of mitochondria between them. These observations support the recent hypothesis that in oxidative muscles the mitochondria and adjacent sarcomeres form complexes, termed as the intracellular energetic units, ICEUs. Moreover, they indicate that human autoantibodies can be useful tools for localizing the proteins responsible for formation of ICEUs and modulation of their function. Thus, it appears that the proteins associated with the Z-disks and M-lines may participate in formation of ICEUs and that binding of IgG to these proteins decreases the access of exogenous adenine nucleotides to mitochondria, which manifests as decreased rate of ADP-dependent respiration.     

Comparison of the prevalence of glutamic acid decarboxylase (GAD65) and gliadin antibodies (AGA) in a randomly selected adult estonian population.

We aimed to test the hypothesis that gluten might be associated with the development of islet cell autoimmunity. A random sample of 200 persons (87 males, mean age 42.4 years) from Estonia including one patient with type I diabetes mellitus was studied. IgG-type glutamic acid decarboxylase (GAD65) antibodies were determined using radioligand-binding assay and IgG/IgA-type gliadin antibodies (AGA) by enzyme-linked immunosorbent assay. Generic HLA-DRB1* alleles were analyzed using a polymerase chain reaction. Although our results revealed the highest GAD65Ab index and a high IgA-type AGA in a person with diabetes, no correlation between GAD65Ab and AGA values was revealed among the other 199 persons (p > 0.05). There were also no differences between test values among persons with and without different HLA-DRB1* alleles (p > 0.05). In the GAD65Ab assay, one person (0.5 %; 95 % CI: 0 - 1.5) out of 199 exceeded the 99(th) centile of the GAD65Ab index. In summary, the present study does not confirm the possibility that there is a relationship between the immune reactivity against GAD65 and gliadin, at least in persons without type I DM.     

Helicobacter pylori infection in children in Estonia: decreasing seroprevalence during the 11-year period of profound socioeconomic changes

BACKGROUND: The prevalence of Helicobacter pylori infection is inversely associated with socioeconomic conditions in childhood. In Estonia, a high prevalence of H. pylori infection has been observed among children born in 1987 and earlier. Since 1991, after the dissolution of the USSR, profound social and economic changes have taken place in the country. The aim of the study was to evaluate changes in the seroprevalence of H. pylori infection among children in the period 1991-2002. MATERIALS AND METHODS: The hospital-based study population consisted of two groups of children enrolled in 1991 (n = 425) and 2002 (n = 296) according to the same inclusion criteria. The immunoglobulin G antibodies to the cell surface proteins of H. pylori were determined by enzyme-linked immunosorbent assay, and the sera with the borderline results were analyzed by immunoblot analysis. Multiple regression analysis was used to determine the associations between H. pylori seropositivity and different variables such as demographic characteristics, diagnoses and year of enrollment. RESULTS: The only two variables linked independently to H. pylori serostatus were age and year of enrollment: the adjusted odds of being H. pylori seropositive were 1.92 [95% confidence interval (CI) 1.33-2.76] times higher for the children enrolled in 1991 compared with the children enrolled in 2002. The age-standardized seroprevalence rate was 42.2% (95% CI 37.4-47.0%) for the group of 1991 and 28.1% (95% CI 23.1-33.6%) for the group of 2002. CONCLUSION: The prevalence of H. pylori infection among children has significantly decreased during the 11-year period of profound socioeconomic changes in Estonia.