The Positivity of Anti-TPO and Anti-tTGA in Children with Type 1 Diabetes Mellitus in Albania

Background: Type 1 diabetes mellitus (T1 DM) is the most common type of diabetes in children. T1DM patients are also at higher risk of other comorbid autoimmune diseases, including autoimmune thyroid disease (AITD), celiac disease (CD). The thyroid-specific immune damage of AITD is strongly associated with elevated serum thyroid peroxidase (TPO). Tissue transglutaminase antibody (tTGA) is a specific antibody and a serological marker of CD. This study aimed to evaluate the positivity of anti - TPO and anti - tTGA in children with T1DM after they were diagnosed. Materials and Methods: This study was conducted from January 2019 to October 2020, included 105 children with T1DM. 44 children matching in aged (1 - 14 years) and gender were taken as control with other diagnoses (16 with viral infection, 24 with short stature, 4 with genetic disorders). The antibodies were checked up for the first time after they were diagnosed. Anti - TPO and anti - tTGA were carried out by ELISA. Results: 55.2% of T1DM children were girls. The anti-TPO was positive in 30.5% of T1DM children compared to 4.5% of children in control group. The anti-tTGA was positive in 7.6% of T1DM children compared to 2.3% of children in control group. Risk of Hashimoto's hypothyroidism was more in children older than 10 years old. 21.9% of children 11 - 14 years old were anti - TPO positive, but it was 16.2%, more common in girls. While, anti - tTGA was positive in 3.85% of children 1 - 5 years old with no difference between boys and girls. Conclusion The most frequent autoimmune disease resulted Hashimoto's hypothyroidism. Girls with T1DM have a higher predisposition to Hashimoto's Hypothyroidism in the 11-14 age group compared to boys. Children with T1DM were found to have a lower predisposition to CD. Children with T1DM have a higher predisposition to develop CD at the age of 1 - 5 years. In conclusion we can say that antibodies to other autoimmune diseases must be performed together with diagnostic examinations for T1DM. Key words: Type 1 diabetes mellitus, Autoimmune Thyroid Disease, Celiac Disease, Thyroid Peroxidase, Tissue Transglutaminase Antibody.

Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).Key points. IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants.

Gluten-related immunogenic peptides in stool as means to monitor compliance with gluten-free diet in children with newly dia gnosed coeliac disease

Objectives and study: To compare the values of gluten-related immunogenic peptides (GIP) in stool and anti-tissue transglutaminase IgA antibodies (anti-tTG IgA) in blood in children newly diagnosed with coeliac disease (CD). Methods: All children (2–15 y) newly diagnosed with CD between May 2018 and May 2020 at our clinic who complied with the inclusion criteria were invited to join the prospective study. During workup for CD, a stool sample to measure GIP was taken together with a blood sample to measure anti-tTG IgA. All newly diagnosed children were invited 4 months later for a check-up. Children and their caregivers were asked about known non-compliance with the gluten-free diet (GFD), a blood sample was taken to measure the anti-tTG IgA, and a stool sample was collected to measure GIP. Blood was evaluated for anti-tTG IgA by ELISA, and the stool was tested by quantitative Sandwich ELISA designed to detect and quantify GIP using the G12 antibody. Values of GIP and anti-tTG IgA were compared in terms of their relation to the upper limit of normal (ULN) of the particular method. Results: 29 children (18 girls) were enrolled in the study. The values of GIP in stool at the time of diagnosis were above the ULN (0.15 µg/g) in all children. Average 4.21, median 3.29, standard deviation (SD) 3.7. After the four months, all but three (89.7%) had values of GIP in the reference range. Average 0.29, median 0.12, SD 0.73. Similarly, anti-tTG IgA values were above the ULN (9.9 U/mL) at the time of diagnosis in all children. Average 164, median 195, SD 49. Although the anti-tTG IgA levels were lower at check-up in all but one child, only 10 (34.5%) showed values within the normal range, with an average of 27.9, median 12.0, and SD 38.9. All children declared strict adherence to GFD. Discussion: Using the GIP concentration in stool, adherence to GFD in our cohort of children is very good, better than that described in literature. Conclusion: Measuring GIP in stool could prove a more sensitive indicator of adherence to GFD in the early months after the diagnosis of CD when anti-tTG IgA are still elevated above the ULN due to their well-described gradual decrease after GFD initiation.

The hidden danger in Syria: Silent Celiac Disease

Celiac disease (CD) is a disorder caused by an aberrant autoimmune response to gluten ingestion in genetically susceptible individuals. Its prevalence nears 1%, and it is not considered typical in the Middle East because of the lack of reports in the Arabic countries. Therefore, this study aimed to define the prevalence of celiac disease in the Syrian community. Healthy young adults and volunteers ranging between 5–65-year-old were tested from December 2018 till May 2019. Samples from the participant's sera were tested for anti-tissue transglutaminase antibody (tTG) IgA/IgG by ELISA using the human recombinant transglutaminase antigen. One hundred participants with a mean ± SD of 22 ± 14 years-old were recruited in the study. Only one participant was suspected of having celiac disease. The mean ± SD of anti-tTG IgA/IgG values were 9.81 ± 9.61 for IgA and 6.64 ± 6.60 for IgG. The study shows no significant difference in IgA or IgG titers between males and females at P = 0.7, P = 0.8, respectively. The estimation of seroprevalence of CD antibodies in a healthy Syrian population is close to 1%. We suggest that the underdiagnosed CD might pose a high risk in Syria, contrary to previous thoughts.

Celiac Disease After Administration of Immune Checkpoint Inhibitors: A Case Report

Immune checkpoint inhibitors (ICI) reinvigorate the immune system to recognize and destroy tumor cells. Because of this biological mechanism, patients might develop autoimmune toxicities, notably in the digestive tract (most frequently, hepatitis or colitis). A 70-year-old man with relapsed mesothelioma was treated with nivolumab in 3rd line. He was hospitalized for watery and foul-smelling diarrhea. He underwent gastrointestinal endoscopy, showing duodenitis and villous atrophy and measurement of serum IgA antibodies to tissue transglutaminase (tTG-IgA+), leading to the diagnosis of ICI-induced celiac disease. He was treated with steroids, proton pump inhibitors, and a gluten-free diet. If ICI-induced celiac disease is rare in the literature, increasing reports suggest that celiac disease might represent an underestimated ICI toxicity. This case highlights the necessity of complementary investigation (including tTG-IgA and endoscopic biopsies) in patients with atypical digestive symptoms during immunotherapy.

Compliance to a Gluten-Free Diet in Swedish Children with Type 1 Diabetes and Celiac Disease

Children with type 1 diabetes (T1D) are at increased risk of celiac disease (CD). The replacement of insulin in T1D, and the exclusion of gluten in CD, are lifelong, burdensome treatments. Compliance to a gluten-free diet (GFD) in children with CD is reported to be high, while compliance in children with both diseases has scarcely been studied. To examine compliance to a GFD in children with both T1D and CD, we analyzed tissue transglutaminase IgA-antibodies (tTGA). Moreover, associations between compliance and age, sex, glycemic control, ketoacidosis (DKA), body mass index (BMI), and time of CD diagnosis were investigated. Of the 743 children diagnosed with T1D in southern Sweden between 2005 and 2012, 9% were also diagnosed with CD. Of these, 68% showed good compliance to a GFD, 18% showed intermediate compliance, and 14% were classified as non-compliant. Higher age, poorer HbA1c, and more DKAs were significantly (p < 0.05) associated with poorer compliance. In conclusion, we found that compliance to a GFD in children with T1D and CD is likely be lower than in children with CD only. Our results indicate that children with both T1D and CD could need intensified dietary support and that older children and children with poor metabolic control are especially vulnerable subgroups.

Cystamine reduces vascular stiffness in Western diet-fed female mice

Consumption of diets high in fat, sugar and salt (Western diet, WD) is associated with accelerated arterial stiffening, a major independent risk factor for cardiovascular disease (CVD). Obese women are more prone to develop arterial stiffening leading to more frequent and severe CVD compared to men. As tissue transglutaminase (TG2) has been implicated in vascular stiffening, our goal herein was to determine the efficacy of cystamine, a non-specific TG2 inhibitor, at reducing vascular stiffness in female mice chronically fed a WD. Three experimental groups of female mice were created. One was fed regular chow diet (CD) for 43 weeks starting at four weeks of age. The second was fed a WD for the same 43 weeks, whereas a third cohort was fed WD, but also received cystamine (216 mg/kg/d) in the drinking water during the last eight weeks on the diet (WD+C). All vascular stiffness parameters assessed, including aortic pulse wave velocity and the incremental modulus of elasticity of isolated femoral and mesenteric arteries, were significantly increased in WD- vs. CD-fed mice, and reduced in WD+C vs. WD-fed mice. These changes coincided with respectively augmented and diminished vascular wall collagen and F-actin content, with no associated effect in blood pressure. In cultured human vascular smooth muscle cells, cystamine reduced TG2 activity, F-actin/G-actin ratio, collagen compaction capacity and cellular stiffness. We conclude that cystamine treatment represents an effective approach to reduce vascular stiffness in female mice in the setting of WD consumption, likely due to its TG2 inhibitory capacity.