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Biomedical subjects

O Simell

Publications and source records attributed to O Simell.

At least 37 records · Page 2Linked to original sources
PubMed2003

Parental nutrition knowledge and nutrient intake in an atherosclerosis prevention project: the impact of child-targeted nutrition counselling.

Most of the counselling in health care targeted at child nutrition is delivered via the parents, but little is known about the effects of such counselling on the nutrition knowledge and dietary habits of the parents. In the Special Turku Coronary Risk Factor Intervention Project for Children (STRIP), we studied how 6.5 years of child-targeted nutrition counselling affected the knowledge, attitudes and dietary habits of the parent mainly responsible for food purchase and preparation. We used a questionnaire and a 24-h recall interview in a time-restricted cohort of 98 families belonging to the intervention group and 89 families belonging to the control group in the STRIP project. After controlling for background variables, the intervention parents had better knowledge than the control parents of causal relationships between food choices and coronary heart disease and of the nutritional composition of foods. Knowledge of nutrition concepts did not differ between the two groups. The quality of fat was better in the diet of the intervention parents, they consumed less salt and they also had more knowledge concerning these subjects compared to the control parents (higher behavioural capability scores). The behavioural capability scores of the total group correlated poorly with their nutrient intakes. Thus, child-targeted nutrition intervention delivered to the parents increased parental nutrition knowledge and improved the quality of the parents' diet. However, as nutrition knowledge of the parents correlated poorly with their nutrient intakes, other factors than knowledge appear to influence parental dietary decisions.

Adult↗
PubMed2003

HLA DR-DQ-encoded genetic determinants of childhood-onset type 1 diabetes in Finland: an analysis of 622 nuclear families.

The diabetes predisposing effect of HLA genes is defined by a complex interaction of various haplotypes. We analyzed the disease association of HLA DRB1-DQA1-DQB1 genotypes in a large nuclear family cohort (n = 622) collected in Finland. Using the affected family based artificial control approach we aimed at characterizing all detectable disease-specific HLA haplotype and genotype effects. The DRB1*0401-DQB1*0302 haplotype was the most prevalent disease susceptibility haplotype in the Finnish population followed by (DR3)-DQA1*05-DQB1*02 and DRB1*0404-DQB1*0302. DRB1*0405-DQB1*0302 conferred the highest disease risk, although this haplotype was very rare. The DRB1*04-DQB1*0304 was also associated with increased disease risk, an effect detected for the first time in the Finnish population. The following haplotypes showed significant protection from the disease and are listed in decreasing order of the strength of their effect: (DR7)-DQA1*0201-DQB1*0303, (DR14)-DQB1*0503, (DR15)-DQB1*0602, DRB1*0403-DQB1*0302, (DR13)-DQB1*0603, (DR11/12/13)-DQA1*05-DQB1*0301, (DR1)-DQB1*0501. In addition to the DRB1*0401/0404-DQB1*0302/(DR3)-DQA1*05-DQB1*02 genotype and DRB1*04-DQB1*0302 homozygous genotypes, heterozygous combinations DRB1*0401-DQB1*0302/(DR13)-DQB1*0604, approximately /(DR8)-DQB1*04, approximately /(DR9)-DQA1*03-DQB1*0303, approximately /(DR1)-DQB1*0501 and approximately /(DR7)-DQA1*0201-DQB1*02 were also disease-associated. As a new finding in this population, the (DR3)-DQA1*05-DQB1*02 homozygous and (DR3)-DQA1*05-DQB1*02/(DR9)-DQA1*03-DQB1*0303 heterozygous genotypes conferred disease susceptibility. Similarly, the DRB1*0401-DQB1*0302/(DR13)-DQB1*0603 genotype was disease predisposing, implying that DQB*0603-mediated protection from diabetes is not always dominant. Comparison of our findings with published data from other populations indicates a significant disease-specific heterogeneity of the (DR8)-DQB1*04, (DR7)-DQA1*0201-DQB1*02 and (DR3)-DQA1*05-DQB1*02 haplotypes.

Adult↗
PubMed2003

The normal population distribution of PRNP codon 129 polymorphism.

OBJECTIVES: The common prion protein gene (PRNP) codon 129 polymorphism modifies the susceptibility to and the phenotype of prion diseases. However, no truly representative normal population-based data, or data stratified according to age or gender are available on the distribution of this polymorphism. MATERIAL AND METHODS: Allelic variation of codon 129 in three Finnish populations representing different age groups, and among Finnish, British and Irish blood donors were examined. RESULTS: The PRNP codon 129 genotype distribution in the total Finnish sample was 49% for methionine-methionine (MM), 42% for methionine-valine (MV) and 9% for valine-valine (VV), for the UK blood donors 42% for MM, 47% for MV and 11% for VV, and for the Irish blood donors 34% for MM, 56% for MV, and 10% for VV. CONCLUSIONS: The genotype frequencies were almost identical in all three Finnish populations of different ages, with no gender differences, and did not differ from corresponding figures for the Finnish blood donors. However, the PRNP codon 129 genotype distribution in Finland differed significantly from that of the British and the Irish blood donors and the previously published blood donor data on other Western Europeans and Americans.

Adolescent↗
PubMed2003

Humoral beta-cell autoimmunity is rare in patients with the congenital rubella syndrome.

The congenital rubella syndrome (CRS) is associated with increased risk for diabetes and thyroid disease. However, the mechanisms by which the rubella virus may cause these diseases are poorly characterized. Previous studies were carried out before modern immunological methods were available. The present study aimed at evaluating whether autoimmune mechanisms are involved in the pathogenesis by analysing antibodies to biochemically characterized autoantigens. The incidence of clinical diabetes, thyroid disease, coeliac disease and related antibodies (islet cell antibodies, ICA; insulin autoantibodies, IAA; antibodies to the tyrosine phosphatase related IA-2 molecule, IA-2 A and glutamic acid decarboxylase, GADA; thyroid peroxidase, TPO; tissue transglutaminase, TTGA; and gliadin, AGA) and HLA risk genotypes were analysed in 37 subjects affected by or exposed to rubella during fetal life (mean age 22.5 years). One patient had diabetes and four patients had clinical hypothyroidism at the time of the examination. ICA, IAA, GADA or IA-2 A were not detected in any of the patients, while five patients tested positive for TPO antibodies. Coeliac disease or TTGA were not observed. Eight patients carried the HLA-DR3-associated HLA-DQB1*02-DQA1*05 haplotype. These results provide no evidence of an increased frequency of markers for humoral beta-cell autoimmunity in patients with CRS suggesting that diabetes in CRS may be caused by other than autoimmune mechanisms.

Adult↗
PubMed2003

A linkage analysis of the CTLA4 gene region in Finnish patients with type 1 diabetes.

The cytotoxic T-lymphocyte antigen 4 (CTLA4) region on 2q33 has been shown to be linked to, and associated with, type 1 diabetes (T1D) and suggested to be one of the loci contributing to diabetes aetiology. The polymorphisms responsible for the effect are yet not defined, and the findings reported for the known markers have been discrepant in various populations. We analysed 15 markers around the CTLA4 gene in 138 Finnish affected sib-pair families. A maximum multipoint LOD score (MMLS) of 0.83 at the CTLA4-(AT)n microsatellite was obtained for the whole data set. When stratified, the MMLS increased to 2.61 in the IBS2 (identical by state 2) dataset. In a transmission/disequilibrium test (TDT), some sex-specific effects were observed in transmissions of alleles of CTLA4-(AT)n and D2S105 in siblings. The transmission of the CTLA4 +49 A/G single nucleotide polymorphism (SNP) did not deviate from the expected frequency in this study. In conclusion, our study confirms the linkage of the CTLA4 region to T1D in the Finnish population. In addition, the observations suggest that the polymorphism actually involved in the disease is not the CTLA4 +49 A/G SNP but a polymorphism in linkage disequilibrium with CTLA4 markers and probably closer to CTLA4-(AT)n than to the CTLA4 +49 A/G SNP.

Antigens, CD↗
PubMed2003

Frequent exposure to invasive medical care in early childhood and operative dental treatment associated with dental apprehension of children at 9 years of age.

AIM: This was to study prospectively a cohort of children as to whether behaviour at a 3-year examination, exposure to medical care and operative dental treatment are associated with each other, and with the level of dental apprehension at 9 years of age. METHODS: Data were collected at three subsequent dental examinations of 126 children (67 boys, 59 girls). Cooperation, general health condition and operative dental treatment during the preceding 3 years were obtained at dental examinations with 3-year intervals, i.e. at 3, 6 and 9 years of age. Children's dental apprehension was assessed at the age of 9 years. The data were analysed using an ordinal logistic regression model. RESULTS: Dental apprehension at 9 years of age was associated with frequent exposure to invasive medical care (p<0.001) and past experience of operative dental care (p<0.002), but not with cooperation at 3 years of age (p=0.124). CONCLUSION: Frequent invasive medical care in early childhood and operative dental treatment, tooth extractions in particular, are associated with dental apprehension at 9 years of age.

Case-Control Studies↗
PubMed2002

Signs of beta-cell autoimmunity and HLA-defined diabetes susceptibility in the Finnish population: the sib cohort from the Type 1 Diabetes Prediction and Prevention Study.

AIMS/HYPOTHESIS: To assess the role of HLA-defined genetic diabetes susceptibility in the appearance of signs of beta-cell autoimmunity in a series of children derived from the general population. METHODS: Tests for five HLA DQB1 alleles and four diabetes-associated autoantibodies were carried out on 1,584 older sibs of infants with an increased HLA-defined genetic risk of Type 1 diabetes. The DQB1 genotypes were classified into those conferring high (* 02/0302), moderate (* 0302/x; where x indicates * 0302 or a non-defined allele), low (* 0301/0302, * 02/0301, * 02/x, * 0302/0602, * 0302/0603; where x indicates * 02 or a non-defined allele) or decreased risk (other genotypes). RESULTS: Both islet cell antibodies (ICA) and GAD65 antibodies (GADA) were more frequent among the sibs with the high-risk genotype than among those with a low or decreased risk. Insulin autoantibodies and IA-2 antibodies (IA-2A) were more prevalent in the high-risk than low-risk sibs. Sibs with moderate-risk genotypes tested positive for ICA, GADA and IA-2A more often than sibs with genotypes conferring decreased risk. Autoantibody titres were also dependent on the genetic risk with high risk sibs having the highest values. Sibs carrying high-risk or moderate-risk genotypes tested positive for multiple antibodies (> or =2) more often than did the sibs with low or decreased genetic risk. CONCLUSIONS/INTERPRETATION: The data show that HLA-defined susceptibility to Type 1 diabetes has an effect on both the quality and quantity of humoral beta-cell autoimmunity in unaffected children derived from the general population.

Antibodies↗
PubMed2002

First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes.

AIMS/HYPOTHESIS: A reduced first-phase insulin response to intravenous glucose is perceived as a sign of far-advanced deterioration of beta-cell function during the development of Type I (insulin-dependent) diabetes mellitus, but data on insulin responses at the onset of diabetes-related autoimmunity are lacking. We studied the first-phase insulin responses of small children soon after observed seroconversion to autoantibody positivity. METHODS: In the Type I Diabetes Prediction and Prevention Study newborn infants are screened for HLA-DQB1-associated genetic risk for Type I diabetes and those with increased risk are followed-up for the emergence of islet-cell antibodies. If antibodies are detected, autoantibodies to three other antigens (insulin, GAD65 and IA-2) are also measured. To measure first-phase insulin responses, intravenous glucose tolerance tests were carried out in 52 (1 to 5-year-old) children who had recently seroconverted to islet-cell antibody positivity. RESULTS: The first-phase insulin response was subnormal (<38 mU/l, the 5(th) percentile of insulin responses of 20 islet-cell antibody negative healthy children at this age) in 22 of the 52 children (42%). Stepwise multiregression analysis showed that islet-cell antibody greater than 20 JDFU (p=0.0005), insulin autoantibodies (p=0.0009) and an increasing number of positive autoantibodies (p=0.0011) were independent predictors of low first-phase insulin response. CONCLUSION/INTERPRETATION: A decreased first-phase insulin response could be an early phenomenon in the course of prediabetes in young children, implying a rapid autoimmune destruction or loss of function of beta cells as well as possible metabolic compensation mechanisms, since 11 out of the 22 high risk children remain nondiabetic for a considerable period of time despite low insulin responses.

Autoantibodies↗
PubMed2002

Peripheral nervous system in gyrate atrophy of the choroid and retina with hyperornithinemia.

OBJECTIVE: To evaluate peripheral nervous system involvement in gyrate atrophy of the choroid and retina with hyperornithinemia (GA). BACKGROUND: GA is an inborn error of amino acid metabolism caused by mutations in the enzyme ornithine aminotransferase. Patients with GA have hyperornithinemia, progressive centripetal loss of vision, minor CNS abnormalities, and type II muscle fiber atrophy with accumulation of tubular aggregates. The authors previously showed that muscle and brain creatine stores are depleted in the patients with GA. METHODS: The authors searched evidence of peripheral nervous involvement in 40 patients with GA (mean age 31.6 +/- 16.3 years; range 5 to 74 years) by using neurography, quantitative sensory threshold testing, and evoked potential testing. RESULTS: Neurography revealed abnormalities in 21 (53%) of the patients. The abnormalities associated with the severity of the ophthalmologic changes and the age of the patients. With quantitative sensory threshold testing, abnormal large-fiber function was found in seven (18%) and abnormal small-fiber function was found in four (10%) patients. Somatosensory evoked potential and brainstem auditory evoked potential responses were abolished in five patients. CONCLUSIONS: These findings of peripheral nervous system involvement in GA suggest that GA is a systemic disease affecting not only CNS but also the peripheral nervous system.

Adolescent↗
PubMed2002

The impact of low-saturated fat, low cholesterol diet on bone properties measured using calcaneal ultrasound in prepubertal children.

To analyze the effects of low-saturated fat, low-cholesterol diet on bone in healthy children, calcaneal ultrasound measurements were obtained in 139 subjects (71 girls, 68 boys; mean age 8 years, SD 0.5), who were recruited from the STRIP (Special Turku Coronary Risk Factor Intervention Project) trial. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and quantitative ultrasound index (QUI) values were determined at the dominant heel using a Hologic Sahara scanner. Values were compared with anthropometry and mean, energy-adjusted dietary intakes (absolute intake/1000 kcal) of fat, carbohydrates, protein, cholesterol, calcium, fiber, and the polyunsaturated to saturated fatty acid ratio derived from 4-day food diaries kept once a year between the ages of 2-7 years. The intakes were also analyzed separately at each time point. The BUA, SOS, and QUI values of the intervention children (n = 90) and the control children (n = 49) were similar. No gender differences were found. BUA correlated with age (r = 0.26, P<0.01), height (r = 0.19, P<0.05), and weight (r = 0.22, P<0.05). QUI correlated with mean intake of fat (r = 0.19, P<0.05) and carbohydrate (r = -0.22, P<0.05), SOS with mean intake of cholesterol (r = 0.18, P<0.05), and BUA with mean intake of carbohydrate (r = -0.22, P<0.05). The intakes of fat and cholesterol were lower (P<0.001) and intakes of protein and carbohydrates higher (P<0.01) in the intervention children, but the intakes of calcium were similar. The differences in the dietary intakes persisted throughout the study period. We conclude that dietary counseling aimed at reducing risk of atherosclerosis in later life does not decrease dietary intake of calcium or diminish the calcaneal ultrasound values in the intervention of children in this study. However, since this study is cross-sectional and only one measurement of bone is used, further studies are needed to draw further conclusions about the influence of dietary counseling on bone health.

Bone Density↗
PubMed2002

Effect of coincident enterovirus infection and cows' milk exposure on immunisation to insulin in early infancy.

AIMS/HYPOTHESIS: Insulin autoantibodies appear often as the first autoantibody in children who develop islet-cell autoimmunity. Our recent studies indicate that primary immunisation to insulin is induced in early infancy by exposure to dietary bovine insulin present in cows' milk formulas. As gut-associated lymphoid tissue is also the primary replication site of enteroviruses, we tested whether enterovirus infections could modify the development of immune response to dietary insulin in early infancy. METHODS: We studied the development of IgG-antibodies to dietary bovine insulin by enzyme immunoassay in relation to enteroviral infections determined by T-cell proliferation response to the Coxsackie B4 virus and by serological tests for enterovirus antigens in 57 infants who carried the HLA DQB1(*)02/0302 diabetes risk genotype and participated in a Finnish population-based birth-cohort study (Diabetes Prediction and Prevention Project, DIPP, study). RESULTS: In the infants exposed to cows' milk formulas before the age of 3 months, those who had a T-cell proliferation response to enterovirus antigen at 3 months of age ( n = 12) had higher concentrations of IgG-antibodies to bovine insulin at the age of 6 and 9 months than those who did not have T-cell proliferation response to enterovirus antigen ( n = 25) (median OD were 0.742 vs 0.427, p = 0.04, and 0.477 vs 0.293, p = 0.02, respectively). CONCLUSION/INTERPRETATION: Our results suggest that two epidemiological risk factors of Type I (insulin-dependent) diabetes mellitus, enterovirus infections and exposure to cows' milk formulas, could modify the immunisation to insulin in early infancy.

Animals↗
PubMed2002

Health-related quality of life in type 1 diabetes without or with symptoms of long-term complications.

OBJECTIVE: To measure subjective health-related quality of life (HRQoL) of patients with type 1 diabetes and describe the influence of symptoms of diabetes-related long-term complications on HRQoL. METHODS: The 15-D health-related quality of life measure (15D) was used to measure HRQoL of a representative sample of Finnish insulin-treated patients expected to have type 1 diabetes. Background data were gathered with a separate questionnaire. A tobit (censored regression) model was constructed to estimate the effects of symptoms of complications on HRQoL and to separate these effects from those of other health problems and aging. RESULTS: The 15D scores declined markedly with increasing age, and the prevalence of symptoms of long-term complications increased. The tobit regression model showed that these symptoms have a significant negative influence on HRQoL. The model explained over 50% of the variation in the 15D scores. CONCLUSIONS: High prevalence of symptoms of long-term complications combined with their significant negative influence on HRQoL causes substantial losses in terms of quality of life and utility from both individual and societal perspectives. Thus, the importance of secondary prevention, i.e., prevention of complications by better metabolic control, and also the so-far theoretic possibility to prevent type 1 diabetes itself is emphasized.

Adolescent↗
PubMed2002

Expression of cyclooxygenase-2 in intestinal goblet cells of pre-diabetic NOD mice.

Cyclooxygenase, the rate-limiting enzyme in prostaglandin synthesis, is expressed in constitutive (COX-1) and inducible (COX-2) isoforms. The COX-2 has been proposed to be involved in development of autoimmune type 1 diabetes (T1D). We examined COX-2 expression in the gut-associated lymphoid tissue (GALT), and found COX-2 was strongly expressed in goblet cells of non-obese diabetic (NOD) mice at the apical villi at the age of 2.5 weeks, clearly before the onset of insulitis, while the expression in the control BALB/c mice was weak or absent at all ages (P < 0.001). Lipopolysaccharide (LPS) given intraperitoneally slightly increased COX-2 expression in the goblet cells and epithelium of both NOD and BALB/c mice. High-resolution confocal microscopy showed that the surroundings of the goblet cells contained no COX-2, implying that the enzyme is synthesized by the goblet cells. The COX-2 is secreted from goblet cells into the intestinal lumen along with mucins. The COX-2 concentration in the goblet cell of BALB/c and especially of NOD mice was markedly higher than that in the intraepithelial lymphocytes or lamina propria macrophages. High mucin COX-2 from goblet cells may increase luminal prostaglandin synthesis, alter epithelial permeability, modulate intestinal immune responses and modify functional properties of the lymphocytes in the GALT, which all may be important for the initiation of the autoimmune phenomenon in the NOD mice.

Animals↗
PubMed2002

Rotavirus infections and development of diabetes-associated autoantibodies during the first 2 years of life.

Rotavirus, the most common cause of childhood gastroenteritis, has been implicated as one of the viral triggers of diabetes-associated autoimmunity. To study the possible association between rotavirus infections and the development of diabetes-associated autoantibodies, we measured the prevalence of rotavirus antibodies in serum samples collected at 3-6-month intervals up to the age of 2 years from 177 children selected from consecutive newborns because they carried HLA-DQB1 alleles associated with increased risk for type 1 diabetes. Twenty-nine of the children developed at least two of four diabetes-associated autoantibodies (ICA, IAA, GADA or IA-2A) during the first 2 years of life (the cases), whereas 148 children remained autoantibody-negative matched with the cases for date of birth, gender, living region and HLA-DQB1 alleles. The temporal association between the development of the first-appearing diabetes-associated autoantibody and rotavirus infections was studied by analysing whether the cases had a diagnostic increase in rotavirus antibody titre more often during the 6-month period that preceded seroconversion to autoantibody positivity than the controls. By the age of 12 months one of the 13 case children (7%), who had a serum sample drawn at that age and who had developed at least one type of diabetes-associated autoantibodies, had experienced a rotavirus infection, while 12 of the 61 (20%) autoantibody-negative control children had had a rotavirus infection. By 18 months, four of the 22 autoantibody-positive cases (18%) and 18 of the 89 controls (20%) had rotavirus antibodies, and by the age of 24 months the respective numbers were five of the 27 cases (19%) and 32 of the 113 (28%) controls. A rotavirus infection occurred during the 6 months preceding the sample which was positive for an autoantibody in four of the 25 periods (16%) for which both necessary samples were available, while the controls had a rotavirus infection during 55 of the 370-such periods (15%). Accordingly, our data suggest that rotavirus infections are unlikely triggers of beta-cell autoimmunity in young children with genetic susceptibility to type 1 diabetes.

Animals↗
PubMed2002

Effects of gender, apolipoprotein E phenotype and cholesterol-lowering by plant stanol esters in children: the STRIP study. Special Turku Coronary Risk Factor Intervention Project.

AIM: To evaluate the effects of gender, apolipoprotein E phenotype and cholesterol absorption and synthesis (estimated as serum plant sterol and cholesterol precursor sterol concentrations) on the cholesterol-lowering effect of plant stanol esters in children. METHODS: Eighty-one healthy, normocholesterolaemic 6-y-old children (45 boys) were recruited from the Special Turku Coronary Risk Factor Intervention Project (STRIP), a randomized prospective trial aiming at atherosclerosis prevention in childhood. This placebo-controlled, double-blind, cross-over study comprised two 3-mo study periods and a 6-wk wash-out period. During the study periods, 20 g of the children's daily dietary fat intake was replaced with plant stanol ester margarine or control margarine. RESULTS: In boys, plant stanol esters reduced serum total and low-density lipoprotein cholesterol concentrations by 6% (0.09 to 0.42 mmol/L) and 9% (0.09 to 0.36 mmol/L), respectively (p < 0.01 for both). In girls, the decreases in concentrations were 4% (0.03 to 0.38 mmol/L) and 6% (0.02 to 0.32 mmol/l) (p < 0.05 for both). The response rate did not differ between the genders. Serum total and low-density lipoprotein cholesterol concentrations decreased by 6% and 8% (p < 0.01 for both), respectively, in both children with the apolipoprotein E 3/4 or 4/4 (apoE4+) phenotype and the apolipoprotein E 2/3 or 3/3 (apoE4-) phenotype. Cholesterol absorption decreased both in the apoE4+ children and in the apoE4- children, but cholesterol synthesis consistently increased in the apoE4+ children only. CONCLUSION: Plant stanol esters reduce serum cholesterol concentration in healthy children irrespective of their gender or apoE4 phenotype.

Apolipoproteins E↗
PubMed2002

Natural history of beta-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes recruited from the general population.

The aim of this study was to evaluate the frequency and predictive value of diabetes-associated autoantibodies, such as islet cell antibodies (ICA) and autoantibodies to insulin (IAA), GAD65 (GADA), and the IA-2 molecule (IA-2A) in genetically susceptible children from the general population during the first 2 yr of life. Of 12,170 newborn infants, 1,005 with increased genetic risk of type 1 diabetes (high risk, human leukocyte antigen DQB1*02/*0302; moderate risk, DQB1*0302/x, where x = other than *02, *0301, or *0602) were monitored for ICA, IAA, GADA, and IA-2A at 3- to 6-month intervals from birth up to a minimum age of 2 yr. In addition, all 15 genetically susceptible children from the general population who had participated in regular immunological follow-up and developed clinical type 1 diabetes by the end of April 2000 were analyzed for the development of autoantibodies. Among 1,005 children, 63 (6.3%) tested positive for at least one autoantibody, 31 for ICA (3.1%), 48 for IAA (4.8%), 23 for GADA (2.3%), and 13 for IA-2A (1.3%) at least once by the age of 2 yr. Both ICA and IAA identified 95% [95% confidence interval (CI), 77.2-99.9%] of those who tested persistently positive for multiple (> or = 2) antibodies at the age of 2 yr, GADA identified 86% (CI, 65.1-97.1%), and IA-2A identified 55% (CI, 32.2-75.6%). Close to half of the antibody-positive children (29 of 63) reverted back to antibody negativity. Autoantibodies disappeared more often among those who tested positive for IAA than among those who tested positive for other autoantibodies (P < or = 0.021). Among the 15 children who developed type 1 diabetes, the disease sensitivity of ICA was 80% (CI, 51.9-95.7%), that of IAA was 93% (CI, 68.0-99.8%), that of GADA was 60% (CI, 32.3-83.7%), and that of IA-2A was 40% (CI, 16.3-67.7%). These results suggest that IAA are characterized by high sensitivity, early appearance, and high frequency of transient antibody positivity, whereas ICA detected with a thoroughly standardized assay appear to be more specific for the screening of beta-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes in the Finnish population, which has the highest incidence of type 1 diabetes in the world.

Aging↗
PubMed2001

Responses of coxsackievirus B4-specific T-cell lines to 2C protein-characterization of epitopes with special reference to the GAD65 homology region.

Coxsackie B viruses (CBV) have been indicated as environmental triggers initiating autoimmune destruction of insulin-producing pancreatic beta-cells, and molecular mimicry might be the mechanism. A prime candidate for inducing cross-reactive immune responses is a homology sequence, PEVKEK, found both in CBV4 2C protein and in GAD65. To characterize the CBV4-specific T-cell epitopes, overlapping peptides covering the 2C protein were synthesized and CBV4-specific T-cell lines were established from healthy and diabetic subjects. The T-cell epitopes were dependent on the HLA-DR genotype of the T-cell donor, but no difference between diabetic and healthy subjects could be detected. Peptide p4, which included the PEVKEK sequence, contained an HLA-DR1-restricted T-cell epitope. Three randomly selected CBV4-specific T-cell lines, which responded to peptide p4, failed to recognize GAD65 protein or GAD65 peptides containing the PEVKEK sequence. We conclude that the CBV4 2C protein is strongly immunogenic for T-cells and PEVKEK is included in a T-cell epitope. However, presentation of this epitope in the context of neutral HLA-DR1 allele does not support its role in pathogenesis of type 1 diabetes.

Adult↗