Styliani Giza

The Role of PTPN22 C1858T Gene Polymorphism in Diabetes Mellitus Type 1: First Evaluation in Greek Children and Adolescents

Type 1 diabetes mellitus (T1DM) is an autoimmune multifactorial disease. Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes lymphoid-specific tyrosine phosphatase (Lyp), an inhibitor of T cell activation. PTPN22 C1858T polymorphism was associated with T1DM in populations of Caucasian origin. The aim of this study was the investigation for the first time of the association of PTPN22 C1858T polymorphism with T1DM in Greek population. We studied 130 children and adolescents with T1DM and 135 healthy individuals of Greek origin. The polymorphism was genotyped using polymerase chain reaction with restriction fragment length polymorphism. C1858T and T1858T genotypes as well as 1858T allele were found more frequently in patients (10.8% and 5.8%, resp.) than in healthy individuals (5.9% and 3.0%, resp.) but at non statistically significant level. There was no statistically significant association found with gender, age at diagnosis, severity of onset, history of Hashimoto thyroiditis or family history of T1DM. Increased frequency of 1858T allele in patients than in controls, implying a probable association, agrees with results of similar studies on other populations. The inability to find a statistically significant difference is probably due to the decreased frequency of minor allele in Greek population, indicating the need for a larger sample.

Suboptimal glycaemic control enhances the risk of impaired prothrombotic state in youths with type 1 diabetes mellitus

Objective: To estimate markers of prothrombotic state and endothelial dysfunction in youths with type 1 diabetes mellitus (T1DM) and investigate possible associations with anthropometric/demographic data, glycaemic control and lipid profile. Methods: In a cross-sectional design, we recruited 155 youths with T1DM and determined levels of plasminogen activator inhibitor-1-antigen (PAI-1-Ag), von Willebrand factor-antigen (vWF-Ag), fibrinogen (FB), lipids and glycosylated haemoglobin (HbA1c). Results: Of all the participants, 76 (49%) had increased levels of at least one of prothrombotic factors. Suboptimal glycaemic control was associated with a worse lipid profile and an eightfold increased risk of elevated vWF-Ag levels. Higher vWF-Ag concentrations were also correlated with impaired lipid profile and increased HbA1c values, whereas PAI-1-Ag was positively correlated only with triglyceride levels. After adjustment for potential confounders, only HbA1c contributed independently to the variation in vWF-Ag levels. Conclusion: Impaired prothrombotic state and consequently endothelial dysfunction are present in youths with T1DM, representing a cumulative risk factor for future cardiovascular disease (CVD). Achievement and maintenance of euglycaemia and normolipidaemia are crucial to decelerate progress of this process.

Prevalence of selective immunoglobulin A deficiency in Greek children and adolescents with type 1 diabetes

BackgroundThe association of selective immunoglobulin A (IgA) deficiency with type 1 diabetes (T1D) remains unclear. This study was to evaluate serum IgA concentrations in Greek children and adolescents with T1D.MethodsIn two hundred individuals with T1D, serum IgA concentrations were quantitatively determined using nephelometry.ResultsImmunoglobulin A deficiency was detected in 6 (3.0%) of 200 patients who were subjected to immunological evaluation. Recurrent infections were not recorded, but human papilloma virus infection was clinically suspected and confirmed by laboratory examination in a 5-year-old girl. In regard to coincidence of selective IgA deficiency with autoimmune diseases, celiac disease was detected in a girl and juvenile idiopathic arthritis in a boy. Serum IgA concentrations differed significantly when patients were grouped according to age at the beginning of the study (P<0.001), age at diagnosis of T1D (P=0.015) and coincidence of celiac disease (CD) (P=0.038). However, when the age of the patients was adjusted, difference in serum IgA concentrations was not statistically significant despite CD was present or not. Moreover, serum IgA concentrations were positively correlated with serum IgG (P<0.001) and IgE (P=0.001) concentrations and negatively correlated with serum antigliadin antibody IgG (P=0.035) concentrations. There was no association or correlation of serum IgA concentrations with glycemic control.ConclusionThe prevalence of selective IgA deficiency in Greek children and adolescents with T1D is high (3.0%). The correlation of serum IgA concentrations with serum IgG, IgE and anti-gliadin antibody IgG concentrations needs further investigation.

Seasonality of month of birth in children and adolescents with autoimmune thyroiditis: a continuing conundrum

Abstract Background The aim of this study was to analyze the seasonal birth month pattern in young patients with autoimmune thyroiditis and compare it with youth controls. Methods Medical records of a total of 298 children and adolescents of Greek origin, with a diagnosis of Hashimoto thyroiditis (HT) before the age of 21 years that were born from 1987 to 2010 were retrospectively reviewed. In addition, 298 consecutive subjects that were born from 1988 to 2012 and evaluated in a tertiary unit for any reason, served as controls, provided that they had no personal or family history of thyroid or any other autoimmune disease. Results Significant differences were found between children and adolescents with HT and healthy controls in the yearly pattern of month of birth distribution (p=0.029). During month-by-month analysis, it was shown that the highest and lowest predispositions to HT were among those born in spring (March) (odds ratio [OR] 2.34, p=0.005), and autumn (November) (OR 0.49, p=0.035), respectively. A binary logistic regression model also revealed that season of birth and sex were the only factors that remained related to HT disease, even after adjustment for confounding factors such as year of birth and age (p<0.001, Nagelkerke r-square 0.151). Conclusions This study suggests that the effect of certain seasonal factors during fetal development, reflected by the seasonal differences in birth pattern, in children and adolescents with autoimmune thyroiditis could contribute to long-term programming of an autoimmune response against the thyroid gland. Further studies are needed to demonstrate a clear cause and effect relationship between month of birth and HT.

l-selenomethionine supplementation in children and adolescents with autoimmune thyroiditis: A randomized double-blind placebo-controlled clinical trial

Although a beneficial effect of selenium (Se) administration has been proposed in adults with autoimmune thyroiditis (AT), there is a paucity of similar data in children and adolescents. The purpose of the study was to investigate whether administration of a high dose of organic Se (200 μg daily as l‐selenomethionine) has an effect on antithyroid antibody titres in children and adolescents with AT.

Osteoprotegerin increases parallel to insulin resistance in obese adolescents

ABSTRACT Purpose/Aim of the Study: Osteoprotegerin (OPG) is an α tumor necrosis factor receptor superfamily glucoprotein that acts as a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL), exerting an antiresoptive bone effect. It was recently shown that OPG/RANKL axis is activated during vascular calcification, contributing to atherosclerotic lesions formation. Additionally, OPG levels are charachterized as an independent risk factor for overall vascular mortality in obese adults. We aimed to investigate OPG levels in children/adolescents with obesity and explore possible relations with obesity-related insulin resistance (IR). Material and Methods: A total of 160 participants (85 obese) were enrolled. Participants with obesity underwent an oral glucose tolerance test. IR was evaluated according to the homeostasis model assessment-insulin resistance index. Serum OPG levels were determined. Results: OPG levels did not differ significantly between obese subjects and controls in the total sample (p = 0.133). However, in the adolescents’ subgroup, serum OPG levels were significantly increased in obesity (p = 0.019). After stratifying participants according to their IR status, only subjects with both obesity and IR exhibited increased OPG levels compared to controls (p < 0.001). Factor analysis further associated OPG levels variation to insulin levels variation and to IR. Conclusions: Obese individuals demonstrate increased serum OPG levels during puberty. Obesity per se is not the potent factor for this increase; indeed, IR accompanying obesity seems to exert a fundamental role in OPG upregulation.

Testicular microlithiasis in a boy with X-linked adrenal hypoplasia congenita

X-linked adrenal hypoplasia congenita (AHC) is a rare disorder that usually presents clinically as adrenal insufficiency in early infancy. It is caused by mutations in the NR0B1 gene which is located on the short arm of chromosome X (Xp21). The NR0B1 gene plays an important role in normal development and function of both the adrenal and gonadal axes and some patients with the disease can present in adolescence with hypogonadotropic hypogonadism. Testicular microlithiasis is an ultrasonographic finding of unknown etiology that has been associated with several benign conditions such as cryptorchidism, congenital adrenal hyperplasia, varicoceles, and testicular malignancy. We report the case of an 11-year-old boy who was diagnosed at the age of 8 months with X-linked AHC due to adrenal failure and presented testicular microlithiasis during follow-up. To the best of our knowledge, this is the first case of an X-linked AHC patient diagnosed with testicular microlithiasis in follow-up.

A case of galactosialidosis with renal failure and hippocampal sclerosis

Galactosialidosis is a rare, recessively inherited lysosomal storage disease, characterized by the combined deficiency of β -D-galactosidase and N-acetyl- α -neuraminidase, due to the genetic alteration of the protective protein/cathepsin A. Its clinical expression varies depending on the age of onset. We report the clinical and biochemical findings of a 15-year-old male who was firstly admitted at the age of 5.5 yr, due to heavy proteinuria, which was followed by progressive renal failure and transplantation at 6.5 yr of age. The diagnosis of galactosialidosis was established by the demonstration of a combined deficiency of neuraminidase β -galactosidase as well as of deficient cathepsin A activity. The renal function started to deteriorate again at the age of 11 yr, when he manifested elements of renal allograft nephropathy. Pyramidal tract dysfunction and generalized tonic-clonic epileptic seizures were added to his clinical picture at that age, whereas his range of movements was clearly compromised due to dysostosis multiplex. A subsequent magnetic resonance imaging demonstrated mild dilatation of the lateral ventricles and cerebral atrophy, as well as hippocampal sclerosis, which may be considered an additional feature of the disease. To the best of our knowledge, this is the first reported patient with galactosialidosis among Greeks.

HLA-DQB1*05 ASSOCIATION WITH HASHIMOTO THYROIDITIS IN CHILDREN OF NORTHERN GREEK ORIGIN

INTRODUCTION: Hashimoto thyroiditis (HT), an organ-specific autoimmune disorder of the thyroid gland, is considered to be associated with the major histocompatibility complex. Association studies of human leukocyte antigens (HLAs) with HT concern adults and have not revealed consistent results. OBJECTIVE: We sought to investigate HLA-DRB1 and HLA-DQB1 gene polymorphisms in Greek children and adolescents with HT. METHODS: We analyzed the distribution of HLA-DRB1 and HLA-DQB1 alleles in 17 Greek children and adolescents with HT and in 181 randomly chosen healthy subjects from northern Greece. The typing of HLA-DRB1 and HLA-DQB1 genes was performed by using polymerase chain reaction with sequence-specific primers. Differences of frequencies for HLA alleles were tested by the χ2 test. RESULTS: There was no significant association detected between HT and HLA-DRB1 or HLA-DQB1 alleles. However, HLA-DRB1*16 was slightly significantly increased in patients with HT (41.2%) compared with that in controls (19.3%) (P = .057; relative risk: 2.92), and HLA-DQB1*05 was significantly increased in patients with an age of diagnosis of >10 years (87.5%) as compared with those with an age of diagnosis of ≤10 years (33.3%) (P = .05; relative risk: 14). CONCLUSIONS: This is the first study to examine children and adolescents from northern Greece with HT and analyze the distribution of HLA-DRB1 and HLA-DQB1 alleles according to the age of onset of HT. However, this study needs to include a greater number of patients to ascertain the possibility of an association and avoid the result of a chance event or random variation.