Tissue Transglutaminase Antibodies Research Articles

Celiac disease (CD) diagnosis: Insights from Albanian serological data integrating anti-gliadin antibodies (AGA) and tissue transglutaminase antibodies (TTA)

Celiac disease (CD) diagnosis: Insights from Albanian serological data integrating anti-gliadin antibodies (AGA) and tissue transglutaminase antibodies (TTA)

Evaluation of the Presentation of Newly Diagnosed Type 1 Diabetes Mellitus in Children During and After the COVID-19 Pandemic

Background: The COVID-19 pandemic has been a global health problem with high morbidity and mortality. In this study, it was aimed to compare the clinical and laboratory findings of patients diagnosed with type 1 diabetes(T1D) during the pandemic and after the pandemic. Method: This is a 30-month, single-center, cross-sectional study. Between October 2020 and December 2021 was defined as the pandemic period, and between January 2022 and March 2023 as the post-pandemic period. The clinical and laboratory parameters of the newly diagnosed T1D patients who applied in these two time periods were compared. Results: While 87 patients were diagnosed during the pandemic period, 86 patients were diagnosed during the post-pandemic period. The rate of male patients diagnosed during the pandemic period was significantly higher (56%, 36%, respectively, p=0.007). Anti-islet Cell antibody (ICA) positivity was statistically significantly higher in those diagnosed during the pandemic period. (52.6%, 18.6%, respectively, p<0.001). There was no difference between the groups in terms of hemoglobin A1C, thyroid autoantibodies and tissue transglutaminase antibodies (p>0.05).C peptide levels were significantly lower in those diagnosed during the pandemic period (0.39±0.4, 0.63±0.6, respectively, p=0.021). Admissions with severe acidosis were more common during the pandemic than those admitted after the pandemic (29.9%, 16.3%, respectively, p=0.151). Conclusions: The numbers of children with T1D newly diagnosed in a secondary health center were similar during and after the pandemic. In the pandemic period, admissions with autoantibody positivity, low C-peptide and severe acidosis were more common.

Correlation between auto-immune diseases and type 1 diabetes mellitus in the pediatric age group in Erbil city

Background and objective: Type-1 diabetes mellitus is the most common chronic endocrine disorder of childhood and adolescence and is characterized by immune-mediated destruction of pancreatic cells, which has been proven to be correlated with and increase the risk of developing autoimmune thyroid disease, celiac disease, Addison’s disease, and further autoimmune diseases. The aim of this study is to evaluate the prevalence of autoimmune disease-related markers in type 1 diabetes mellitus in children and adolescents in Erbil city. Methods: One hundred children and adolescents with type 1 diabetes mellitus were enrolled in this cross-sectional study. Patients <1 year old were excluded from the study. Autoimmune thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) along with tissue transglutaminase (IgA and IgG) antibodies were measured with further evaluation by thyroid function test and endoscopy with biopsy (for positive serological autoantibodies level). Results: Elevated anti-thyroglobulin, anti-thyroid peroxidase, and tissue transglutaminase IgA and IgG antibodies were determined in 24.0%, 26%, 10%, and 8%, respectively. 50.0% of cases with positive anti-thyroid peroxidase antibodies had overt hypothyroidism; on the flip side, 3.8% had subclinical hypothyroidism. As well, the high level of thyroid autoantibodies was significantly correlated to the prevalence of overt hypothyroidism (P <0.001). Nine of the patients with positive tissue transglutaminase antibodies were verified to have biopsy-proven celiac disease. Conclusion: Children and adolescents with type 1 diabetes mellitus are at risk of developing positive antithyroid and celiac-related autoantibodies, so they are at risk of progressing to autoimmune thyroid and celiac diseases.

Case report: Multiple autoimmune syndrome

This is a case of multiple autoimmune syndrome with the co-occurrence of vitiligo, pernicious anemia, celiac disease and autoimmune hepatitis is extremely rare. We are presenting a case is a 40-year-old woman with autoimmune hepatitis who is suffering from poor appetite, weight loss and skin lesions. Laboratory investigation shows hypochromic microcytic anemia, B12, and iron deficiency. The testing for parietal cell antibody was positive so pernicious anemia was diagnosed with positive Tissue transglutaminase antibody IgA so the diagnosis of celiac disease was confirmed.

Path Towards Biopsy-Free Diagnosis of Celiac Disease in Pediatric Patients

BackgroundLaboratory testing for celiac disease in pediatric patients integrates serology, genetic susceptibility and duodenal biopsy examination. The 2023 American College of Gastroenterology guidelines recommend a biopsy-free approach in pediatric patients utilizing tissue transglutaminase antibody titers >10 times upper limit of normal and subsequent endomysial antibody seropositivity as sufficient for diagnosis. The objective of this study is to assess the diagnostic accuracy of biopsy-free approach at our pediatric hospital. MethodsWe conducted a retrospective study involving pediatric patients who underwent biopsy for diagnostic confirmation of celiac disease between May 2019 and May 2023. For these patients, the tissue transglutaminase and endomysial antibody test results were retrieved and performance of biopsy-free approach was assessed using the duodenal histology as the gold standard for celiac disease diagnosis. ResultsTissue transglutaminase antibody titers >10 times upper limit of normal alone demonstrated a positive predictive value of 99% for identifying celiac disease in children. Although endomysial antibody testing is underutilized at our center, its inclusion further improved the predictability to 100 %. ConclusionPositive predictive value of tissue transglutaminase antibody titers >10 times upper limit of normal is sufficiently high for celiac disease diagnosis in children and may allow for deferral of duodenal biopsy at diagnosis.

A174 TESTING FOR AND INCIDENCE OF CELIAC DISEASE AUTOIMMUNITY SAW SIGNIFICANT BUT TEMPORARY DECLINES DURING COVID-19 PANDEMIC

Abstract Background Celiac disease (CD) is an autoimmune disorder with various complications and long-term health risks. The COVID-19 pandemic affected the entire healthcare system—including screening for and diagnosing non-infectious conditions. Aims Determine how the COVID-19 pandemic affected the testing for, and incidence of, CD autoimmunity. Methods Using the population-based Alberta Medical Laboratory database, all tissue transglutaminase antibody tests (tTG-IgA) were identified in Alberta (April 2012 to March 2023). Incident cases of CD autoimmunity comprised of individuals newly positive for tTG-IgA between April 2015 and March 2023. Prevalent cases of CD were excluded based on previous tTG-IgA positivity and/or CD diagnosis codes in outpatient or inpatient settings. Average monthly percent changes and inflection points for testing and incidence rates were estimated using Joinpoint regression. Autoregressive integrated moving average models were performed to forecast rates if the pandemic had not occurred. Incidence rate ratios (IRRs) were estimated to compare a pre-pandemic era (April 2017 to March 2020) and a pandemic era (April 2020 to March 2023) overall and across subgroups. Results In the pandemic era, 311,971 tTG-IgA tests were performed on 284,882 unique individuals (21.1 per 1000 person-years (Table 1)). Testing decreased by 23.4% per month from February 2020 until May 2020 (Figure 1A). From June 2020 to August 2020, testing rates increased by 22.3% per month and then remained stable until the end of the study period. There were 4907 new cases of CD autoimmunity in the pandemic era, with an incidence of 36.3 per 100,000 person-years (Table 1). Incidence rates decreased by 14.1% per month from January 2020 until April 2020 (Figure 1B). Subsequently, incidence continued to rise by 2.0% per month from May 2020 until the end of the study period. Conclusions The COVID-19 pandemic appears to have had a minor impact on identifying potential CD. Future surveillance is needed to determine if the pandemic affected the diagnostic pathway to biopsy-confirmed CD through upper endoscopy procedures and any adverse outcomes individuals may have had from delayed diagnosis. Table 1: Testing and incidence rates for CD autoimmunity in Alberta in pre-pandemic era (April 2017 to March 2020) and pandemic era (April 2020 to March 2023) IRR=incidence rate ratio; CI=confidence interval Figure 1: Testing (A) and incidence (B) rates for CD autoimmunity before and after the start of the COVID-19 pandemic Funding Agencies CAG, CIHRhttps://triangleprogram.org

Clinical and immunological characteristics of children diagnosed with-Type 1 diabetes during the COVID-19 pandemic.

To find clinical and immunological signatures of the SARS-CoV-2 and the COVID-19 pandemic on children newly diagnosed with type 1 diabetes (T1D). A single-centre, retrospective, observational study comparing the clinical and immunological characteristics of children diagnosed with T1D the year before and during the first 2 years of the COVID-19 pandemic. Data extracted from the medical records included clinical and demographic parameters, COVID-19 PCR results and the presence of anti-islet, thyroid and celiac-related antibodies. Also obtained from the medical records was a family history of T1D, celiac disease and autoimmune thyroid disease in a first-degree family member. A total of 376 children were diagnosed with T1D during the study period. A total of 132 in the pre-COVID era and 246 in the first 2 years of the pandemic. At diagnosis, the pH in children with DKA was lower, and HbA1c tended to be higher in the COVID-19 group compared to the pre-COVID-19 group (7.30 [7.18, 7.35] vs 7.33 [7.19, 7.36], p = 0.046) and (110.9 [86.9, 129.5] vs 100 [80.3, 129.5], p = 0.067]) respectively. Multiple islet antibodies (IA) were significantly more common among patients in the pre-COVID-19 group compared to the COVID-19 group (72% vs 61%, p = 0.032). Tissue transglutaminase antibodies were more common among children diagnosed in the COVID-19 compared to the pre-COVID group (16.6% vs 7.9%, p = 0.022). Our findings suggest that SARS-CoV-2 and the environmental alterations caused by the pandemic affected the clinical characteristics and the immunological profile of children diagnosed with T1D. It is, therefore, plausible that the virus plays a role in the autoimmune process causing T1D.

Trends in the prevalence rates and predictive factors of coeliac disease: A long-term nationwide follow-up study.

The prevalence of coeliac disease doubled in Finland from 1980 to 2000. To investigate whether this increase is continuing and if there are specific patient-related factors predicting the development of coeliac disease at a population level. We elicited comprehensive health data in the nationwide Health 2000 and Health 2011 surveys. Serum samples were taken for the measurement of tissue transglutaminase antibodies (TGA); subjects who were seropositive were tested for endomysial antibodies (EmA). Coeliac disease was defined either as a reported diagnosis or as positive TGA and EmA. The surveys comprised, respectively, 6379 and 4056 individuals, forming representative samples for 2,946,057 and 2,079,438 Finnish adults. Altogether 3254 individuals participating in both surveys comprised a prospective follow-up cohort. Prevalence of coeliac disease was 2.12% in 2000 and 2.40% in 2011 (p = 0.156). In the prospective cohort, 16 out of the 3254 (0.49%) subjects developed coeliac disease during follow-up from 2000 to 2011, with an annual incidence rate of 45 per 100,000 persons. Positive TGA without EmA (OR: 133, 95% CI: 30.3-584), TGA values in the upper normal range (51.1, 16.0-163), and after adjusting for TGA, previous autoimmune co-morbidity (8.39, 4.98-35.9) in 2000 increased the likelihood of subsequent coeliac disease. The nationwide prevalence of coeliac disease kept on rising from 2.12% in 2000 to 2.40% in 2011 in Finland. Positive TGA without EmA, TGA titres in the upper normal range and a pre-existing autoimmune disease predisposed to coeliac disease during the 10-year follow-up.

The Importance of Biomarkers in the Diagnosis and Follow-Up of the Celiac Disease

Aim: In the present study, the purpose was to investigate the clinical significance, diagnostic capabilities, relationships, and correlations of inflammation-based biomarkers before and after treatment in children with Celiac Disease. Methods: The study was conducted by retrospectively evaluating the files of patients who were diagnosed and followed up in the Department of Pediatric Gastroenterology of Selçuk University between January 2011 and January 2023. The study was completed with 202 Celiac Disease patients who were diagnosed according to the criteria of the European Pediatric Gastroenterology, Hepatology, and Nutrition Community and 160 healthy follow-ups. In case of clinical or laboratory suspicion, serological tests such as positive Tissue Transglutaminase Antibody and Anti-Endomysium values and the histopathological examination of the endoscopic tissue sample findings consistent with Celiac Disease were evaluated. Results: There were 122 (56.7%) girls and 80 (54.4%) boys in the patient group and 93 (43.3%) girls and 67 (45.6%) boys in the control group. The most common intestinal complaint was abdominal pain in 49 (22.3%) patients. Gluten-free diet treatment was started after the diagnosis. The values of the patients at the time of diagnosis, in the 6th month after the diet, and the values of healthy control patients were compared. A weak and positive correlation was found between NLR, RPO, RLO levels, and age, body weight, and height in the correlation analysis. The ROC curve for hematological biomarkers was used to evaluate the level of additional diagnostic support in Celiac Disease patients. Conclusion: After a gluten-free diet, symptoms regress, and the development of more serious celiac-related damage can be prevented. This suggests that NLR, RLR, PLO, SII, HRO, and PNI formulas, which are used in many inflammatory conditions and obtained from routine hemogram parameters, can be used to determine dietary compliance in Celiac Disease patients during their follow-ups.

THU439 Baby's Coming, Break A Leg! A Case Of Transient Osteoporosis Of The Hip

Abstract Disclosure: A. Khan: None. A. Syeda: None. H.B. Aftab: None. Introduction: Pregnancy-associated osteoporosis (PAO) is a rare condition presenting as fragility fractures usually in the latter part of pregnancy or immediate postpartum period. Vertebral fractures are more commonly reported but femoral fractures have also been described in the literature as a distinct entity: transient osteoporosis of the hip (TOH). We present a case of bilateral (B/L) femoral fractures in a woman during pregnancy and in the postpartum period. Case: A 31-year-old, gravida 1 female developed left leg pain at 26 weeks of gestation. The pain radiated from her left lower back to her left knee. It was severe in intensity resulting in her walking with crutches. Subsequent MRI of the left hip showed subchondral insufficiency fracture of the femoral head with prominent bone marrow edema extending from the head into the femoral neck. She was managed conservatively with non-weight bearing status and oral analgesics. She had an uncomplicated vaginal delivery at 39 weeks of gestation. During the first postpartum week she developed right hip pain. MRI of right hip revealed nondisplaced right femoral head subchondral insufficiency fracture with associated effusion and synovitis. She recovered within the next 3 months with resolution of her pain with conservative management. Other than limited calcium intake in childhood, there were no other identifiable risk factors for osteoporosis. Bone density scan revealed normal Z-scores at the lumbar spine and non-dominant wrist. The hips were not evaluated. Workup for secondary causes of osteoporosis was unremarkable including normal serum calcium, PTH, phosphorus, magnesium, SPEP, tissue transglutaminase antibodies, estradiol, LH, FSH, prolactin levels. However, 24-hour urine calcium level was low at 11 (35-250) mg/24hr. Elevated levels of bone specific alkaline phosphatase and urine N-telopeptide (NTX) were noted at 19.9 (5.3-19.5) mcg/L and 110 (4-64) nM BCE/mM creatinine, respectively. Patient was continued on vitamin D and calcium supplements. She breastfed for the initial 2 months but was advised to stop. At her most recent follow up visit 4 months postpartum patient was doing well. Discussion: TOH is a rare entity, and presentation as B/L femoral fractures is exceedingly rare. During pregnancy and lactation, the skeletal system undergoes bone loss to compensate for the calcium demand of the fetal skeletal system. In TOH, venous stasis from the gravid uterus resulting in bone marrow edema is the proposed mechanism in addition to pregnancy associated bone loss. In our patient, a low 24-hr urine calcium could suggest low calcium intake which could have contributed to the fracture as well. While recurrence of PAO has been described, no recurrence of TOH has been reported in subsequent pregnancies. Our case highlights the importance of keeping this rare entity on the differential in pregnant women presenting with back or hip pain. Presentation: Thursday, June 15, 2023

Serological Screening for Celiac Disease and Gastrointestinal Absorption Disorders in Patients with Autoimmune Endocrine Diseases.

Celiac disease (CD) accompanying autoimmune endocrine diseases (AED) is generally asymptomatic. This study aimed to evaluate the frequency of clinically overt or silent CD in patients diagnosed with autoimmune endocrinopathy and the clinical effects of silent CD in these endocrinopathies. The study included 166 patients with known or newly diagnosed mono-/polyglandular AED and 90 age- and gender-matched healthy controls. The patients were classified into four groups: type 1 diabetes mellitus (DM) (n=44), Hashimoto's thyroiditis (HT) (n=68), Addison's disease (AD) (n=17), and autoimmune polyglandular syndrome (APS) (n=37). All subjects were serologically screened for tissue transglutaminase antibody (tTG) IgA and IgG. In addition, to evaluate the possible systemic consequences of CD, serum parathormone (PTH), 25-hydroxicholecalsiferol (25-OH-Vit D), vitamin B12, folic acid, iron, iron-binding capacity (IBC), and ferritin levels were measured. In the total series, 193 (75.4%) individuals were females, and 63 (24.6%) were males. TTG IgA antibody positivity was found in 23 among 166 patients, while no positivity was encountered in the healthy control group. The highest rates of positive tTg IgA frequency were detected in AD, with 29.4% (5/17). Serum 25-OH-Vit D, vitamin B12, folic acid, iron, and ferritin levels were significantly lower in AEDs compared to controls (p<0.001), and the lowest these parameters were detected in patients with AD. The serologic CD prevalence is higher in autoimmune mono-/and polyglandular endocrine diseases than in the control group. The data support recommends regular screening for CD in all patients with AEDs.

Prevalence of tissue transglutaminase antibodies and IgA deficiency are not increased in juvenile idiopathic arthritis: a case-control study

BackgroundThe prevalence of Celiac Disease (CD) in Juvenile Idiopathic Arthritis (JIA) has been reported to be 0.1–7% in various small studies. As a result of the limited number of research and their inconclusive results there are no clear recommendations for routine CD screening in asymptomatic patients with JIA. Our aim is to estimate the prevalence of IgA deficiency and tissue transglutaminase (tTG) IgA in a cohort of JIA followed in two large academic medical centers.MethodsSerum was collected and stored from all subjects and analyzed in a reference laboratory for total IgA (Quantitative Nephelometry) and tTG IgA antibody levels (Semi-Quantitative Enzyme-Linked Immunosorbent Assay). Fisher’s exact tests were performed for statistical significance. Risk estimates (odds ratios) with 95% confidence intervals were calculated.Results808 JIA cases and 140 controls were analyzed. Majority were non-Hispanic whites (72% vs. 68% p = 0.309). A total of 1.2% of cases were IgA deficient compared to none of the controls (p = 0.373). After excluding IgA deficient subjects, 2% of cases had tTG IgA ≥ 4u/mL compared to 3.6% of controls (p = 0.216) (OR = 0.5; 95% C.I = 0.1–1.4); and 0.8% of cases had tTG IgA > 10u/mL compared to 1.4% of controls (p = 0.627) (OR = 0.5; 95%C.I = 0.1–2.9).ConclusionsUsing the largest JIA cohort to date to investigate prevalence of celiac antibodies, the prevalence of positive tTG IgA was 0.8% and of IgA deficiency was 1.2%. The results did not demonstrate a higher prevalence of abnormal tTG IgA in JIA. The study did not support the routine screening of asymptomatic JIA patients for CD.

Unique presentation of Mauriac syndrome with associated celiac disease in an adolescent with type 1 diabetes mellitus: A case report

We report an adolescent girl with Mauriac syndrome diagnosed in merely 3 years of diagnosis of type 1 diabetes mellitus with poor glycemic control and associated celiac disease. A 11-year-old girl with poor metabolic control characterized by recurrent hypoglycemia and hyperglycemia presented with Mauriac syndrome comprising stunting, hepatosplenomegaly, and elevated serum transaminases without cushingoid features, within 3 years of diagnosis of type 1 diabetes mellitus. Serum tissue transglutaminase antibodies were elevated. The girl also had coexisting celiac disease. She improved with adequate glycemic control along with a gluten-free diet, iron, and other supplements with regression in the size of the liver and reduction of liver enzymes. Mauriac syndrome should be considered in type 1 diabetic patients with poor metabolic control and hepatomegaly irrespective of the duration of diabetes mellitus. Recurrent hypoglycemia and the presence of Mauriac syndrome are signs of associated autoimmune disorders.

Lack of Follow-Up for Celiac Disease During Childhood Not Associated With Poor Health Outcomes: A Regional Swedish Cohort Study.

The objective of the study is to examine the association between the lack of follow-up for celiac disease (CD) during childhood and dietary adherence, disease remission, and health-related quality of life (HRQoL). We invited 243 randomly selected children diagnosed with CD in 2013-2018 in Gothenburg, Sweden, and 162 consented to participate (67%). We retrieved information on clinical follow-up and current wellbeing using medical and laboratory records data, as well as validated questionnaires on symptoms of CD, dietary adherence, and HRQoL. We analyzed tissue-transglutaminase antibodies (tTGA) as a measure of disease remission. We defined lack of follow-up as no CD-related physician/dietician-led visit or measurement of tTGA over the past 24 months of study enrollment. The mean age at study enrolment was 12.7 (range 7.8-18.2) years. Out of 162 children with an average disease duration of 5.3 (range 2.3-8.8) years, 23 (14%) lacked follow-up. tTGA had normalized in 94% [95% confidence interval (CI) = 71%-100%] of children without follow-up versus 91% (95% CI: 85%-95%) of children with continued follow-up. Of children without follow-up, 65% (95% CI: 38%-86%) reported a dietary adherence score indicating very good adherence, versus 72% (95% CI: 63%-80%) of those with continued follow-up. Also, lack of follow-up was not significantly associated with growth, symptom scores, or HRQoL. In this regional cohort study of mostly older children and adolescents, lack of follow-up for CD was not significantly linked to dietary adherence, disease remission, or HRQoL. How these results hold in larger, unselected samples with longer follow-up, including transition to adult care, warrants further study.

Evaluation of Serum Ghrelin and Leptin Levels in Patients with Celiac Disease, Type1Diabetes Mellitus and Rheumatoid Arthritis

Ghrelin and leptin are two hormones that possess multiple functions, including appetite regulation, maintenance of the tissue homeostasis and regulation of proinflammatory cytokines. A few studies on serum ghrelin and leptin levels in autoimmune diseases have exhibited conflicting results. Therefore, the present study aimed to investigate the relationship between the two energy balance hormones and autoimmune diseases. Serum ghrelin and leptin levels were assessed in 94 adult patients, 61 females and 33 males, with various autoimmune diseases (celiac disease, type 1 diabetes mellitus and rheumatoid arthritis) as well as in 35 healthy people as controls, using commercially available ELISA kits. Statistically important distinctions (P &lt; 0.05) were found between the patients and controls with regard to serum ghrelin and leptin levels. Moreover, females had higher mean serum ghrelin and leptin levels than males. On the other hand, serum ghrelin level was positively correlated with serum leptin levels (r = 0.399, P &lt; 0.05) in the RA group. Whereas no significant correlation (P &gt; 0.05) was found between serum ghrelin and leptin levels in both CD and T1DM groups. As well as the correlation of the diseases biomarkers (tissue transglutaminase antibodies, anti-tTG; glutamic acid decarboxylase antibodies, anti-GAD; and cyclic citrullinated peptide antibodies, anti-CCP) with ghrelin/leptin levels revealed that anti-CCP was the only marker that significantly (P &lt; 0.05) associated with ghrelin and leptin in patients with RA. The current study indicates a linkage between the immune system and metabolic hormones depending on response to different autoimmune conditions. Additional studies are required to understand whether changes in ghrelin-leptin levels influence the emergence of autoimmune diseases or vice versa.

#3121 THE EFFECTIVENESS OF A GLUTEN-FREE DIET IN PATIENTS WITH IGA NEPHROPATHY

Abstract Background and Aims Modern data from the world literature confirm the association of IgA nephropathy (IgAN) and celiac disease. The inclusion of a gluten-free diet (GFD) in the diet has a beneficial effect not only on gastrointestinal symptoms, but also reduces the clinical and laboratory activity of IgAN. The aim of this study was to evaluate the effect of a gluten-free diet on the course of IgAN using general clinical and immunological tests 6 months after the start of its use. Method 65 patients with morphologically confirmed IgAN were included in the study. To detect a violation of gluten metabolism, screening determination of the level of IgA antibodies to tissue transglutaminase (Anti-TTG IgA) and IgA antibodies to deamidated gliadin peptides (Anti-DPG IgA) was performed. According to the results of the screening examination, a group of patients with the level of antibodies exceeding the reference values were formed (group 1, n = 13) and a group of patients in whose blood did not exceed the reference values, or were absent at all (group 2, n = 52). Patients of both groups were recommended GFD for a period of at least 6 months. The effectiveness of GFD was evaluated by the following indicators: protein in urine (g/l); red blood cells in urine (RBCs) (hpf); daily proteinuria (g/day); blood creatinine (mmol/l), GFR calculated by the formula CKD-EPI (ml/min /1.73 m2) at the beginning of the study and 6 months after the inclusion of dietary recommendations. Statistical analysis of the data obtained was carried out using the statistical program SPSS Statistics 26.0 (IBM, USA). When comparing quantitative indicators, the distribution of which differed from normal in two related groups, the Wilcoxon criterion was used. The null statistical hypothesis about the absence of differences and connections was rejected at p&amp;lt;0.05. Results among the examined patients there were 61 men (93.8%), 4 women (6.2%). The average age of men was 39.0±8.2 years, women - 34.7±9.7 years. The duration of the underlying disease at the time of inclusion in the study was 55.98 [40.67-71.28] months. 57 people (85.1%) received ACE inhibitors/sartans in therapeutic doses as the main therapy, 8 people (11.9%) did not receive drug therapy. It was possible to evaluate the effectiveness of GFD in patients from group 1 in 9 people. During the follow-up period, 2 patients from group 1 showed progression of the disease to the End-Stage Renal Disease (GFR according to CKD-EPI &amp;lt;15 ml/min/1.73 m2), which required their exclusion from the study, in 2 more patients it was not possible to evaluate the effectiveness of GFD due to insufficient follow-up periods (less than 6 months.) GFD was also recommended to patients from group 2. Dietary restrictions were applied to patients with daily protein loss &amp;gt; 0.5 g/day and/or anti-TTG IgA and anti-DPG IgA levels in the range of pre-reference values, thus it was possible to evaluate the effectiveness of GFD in patients of group 2 in 21 people. According to the results of the analysis, a statistically significant decrease in daily proteinuria (p = 0.028) and microscopic hematuria (p = 0.018) was revealed. After 6 months from the start of compliance with GFD, daily proteinuria decreased in 66.7%; microscopic hematuria – in 77.8% in group 1 patients. Among group 2 patients, a statistically significant decrease in microscopic hematuria (p = 0.05) was observed in 76.2% of those included in the study. Conclusion the inclusion of GFD in the diet of patients with IgAN is justified in patients with the presence of gluten antibodies in the blood serum, as it allows to significantly reduce the severity of proteinuria, microscopic hematuria in these patients. Screening examination of patients with IgAN for gluten metabolism disorders will expand therapeutic possibilities, and GFD can become part of a nephroprotective strategy.

Endocrinological, immunological and metabolic features of patients with Fabry disease under therapy.

Fabry disease is an X-linked lysosomal disorder caused by decreased or absent alpha galactosidase enzyme. The enzyme deficiency leads to progressive accumulation of globotriaosylceramide (Gb-3) and its deacetylated form lyso-Gb3 in various tissue lysosomes that results in primarily lysosomal deterioration and subsequently mitochondrial, endothelial, and immunologic dysfunctions. The endocrinological, metabolic, immunological and HLA status of 12 patients were evaluated. A total of 11 patients (91.6 %) had immunologic and/or endocrinologic abnormalities. fT4, anti-TPO, and anti-TG levels were increased in 1, 2, and 2 patients, respectively. Three patients had elevated proinflammatory cytokines. ANA profile, p-ANCA and c-ANCA were positive in 1, 1, and 2 patients, respectively. Tissue transglutaminase antibody was negative in all patients however P5 was diagnosed with Celiac disease at the age of 12 and on gluten free diet. All patients had distinct types of HLA apart from 2 patients with anti-TG and anti-TPO positive and there was no relationship between the HLA types and the autoimmunity biomarkers. FD may have impact on endocrinologic and immunologic abnormalities even in the patients under ERT, therefore prevalence of these abnormalities may be higher in ERT naïve patients. However, apparently, they are less likely to cause clinical symptoms. Certain HLA alleles may contribute to the direct impact of immunological pathogenesis in FD by developing abnormal autoimmune biomarkers. To the best of our knowledge, this is the first study investigating HLA status of FD patients; therefore further studies are needed to elucidate the underlying mechanism of action.

The risk for celiac disease after Covid-19 infection

BackgroundCeliac disease (CD) is an autoimmune disease leading to gastrointestinal symptoms and mineral deficiencies. The pathogenetic mechanisms, besides the clear HLA association, are elusive. Among environmental factors infections have been proposed. Covid-19 infection results in a systemic inflammatory response that often also involves the gastrointestinal tract. The aim of the present study was to investigate whether Covid-19 infection could increase the risk for CD.Patients and methodsAll patients, both children and adults, in the county Skåne (1.4 million citizens) in southern Sweden with newly diagnosed biopsy- or serology-verified CD or a positive tissue transglutaminase antibody test (tTG-ab) during 2016–2021 were identified from registries at the Departments of Pathology and Immunology, respectively. Patients with a positive Covid-19 PCR or antigen test in 2020 and 2021 were identified from the Public Health Agency of Sweden.ResultsDuring the Covid-19 pandemic (March 2020 – December 2021), there were 201 050 cases of Covid-19 and 568 patients with biopsy- or serology-verified CD or a first-time positive tTG-ab tests, of which 35 patients had been infected with Covid-19 before CD. The incidence of verified CD and tTG-ab positivity was lower in comparison to before the pandemic (May 2018 – February 2020; 22.5 vs. 25.5 cases per 100 000 person-years, respectively, incidence rate difference (IRD) -3.0, 95% CI -5.7 – -0.3, p = 0.028). The incidence of verified CD and tTG-ab positivity in patients with and without prior Covid-19 infection was 21.1 and 22.4 cases per 100 000 person-years, respectively (IRD − 1.3, 95% CI -8.5–5.9, p = 0.75).ConclusionsOur results indicate that Covid-19 is not a risk factor for CD development. While gastrointestinal infections seem to be an important part of the CD pathogenesis, respiratory infections probably are of less relevance.

Prevalence of Organ-Specific Autoimmunity in Patients With Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) is associated with other autoimmune disorders that are characterized by presence of organ-specific autoantibodies. The present study was undertaken to assess theprevalence of organ-specific autoantibodies amongnewly diagnosed T1DM subjects of Indiaand to studyits relationshipwith glutamic acid decarboxylase antibody (GADA). We also compared the clinical and biochemical parameters in GADA-positive and -negative T1DM subjects. In a hospital-based cross-sectional study, we studied 61 patients with newly diagnosed T1DM ≤ 30 years of age. T1DM was diagnosed on the basis of acute onset of osmotic symptoms with or without ketoacidosis, severe hyperglycaemia [blood glucose > 13.9 mmol/l (>250 mg/dl)] and insulin requirement from the onset of diabetes. Subjects were screened for autoimmune thyroid disease (thyroid peroxidase antibody [TPOAb]), celiac disease (tissue transglutaminase antibody [tTGAb]), and gastric autoimmunity (parietal cell antibody [PCA]). Of the 61 subjects, more than one-third (38%) had at least one positive organ-specific autoantibody. In particular, 13 (21.3%) were found to be positive for TPOAb, nine (14.8%) were positive for tTGAb and 11 (18%) were positive for PCA. GADA was positive in 15 (25%) subjects.The frequency of TPOAb tended to be higher in patients who had GADA positivity compared with those with no circulating GADA (40% vs.15.2%;p=0.07). Subjects positive for GADA were also more likely to be PCA positive compared with those who were GADA negative (40 vs.10.9%, p=0.02). There were no differences in frequency of diabetic ketoacidosis, body mass index, hemoglobin A1C (HbA1c), insulin requirement or fasting C-peptidein GADA-positive and -negative patients. We support the recommendation for regular screening of organ-specific autoantibodies, in particular TPOAb, tTGAb and PCA in all patients with T1DM. Detection of these autoantibodies at onset may prevent complications associated with delayed diagnosis of these disorders. We also conclude that there is higher frequency of TPOAb and PCA in GADA-positiveT1DM patients as compared to negative ones. However, patients with positive GADA had similar clinical and biochemical parameters compared to GADA-negative subjects. Lastly, low GADA positivity in our study cohort as compared to Western populations suggests the heterogenous nature of T1DM in the Indian population.

Evaluation of a Single Determination of Gluten Immunogenic Peptides in Urine from Unaware Celiac Patients to Monitor Gluten-Free Diet Adherence.

Usually, adherence to the gluten-free diet (GFD) in celiac patients is indirectly assessed through serological analysis, questionnaires, or invasive methods such as intestinal biopsy. The detection of gluten immunogenic peptides in urine (urinary gluten immunogenic peptides-uGIP) is a novel technique that directly evaluates the ingestion of gluten. The aim of this study was to evaluate the clinical efficacy of uGIP in the follow-up of celiac disease (CD). From April 2019 to February 2020, CD patients reporting complete adherence to the GFD were prospectively enrolled but were unaware of the reason for the tests. Urinary GIP, the celiac dietary adherence test (CDAT), symptomatic visual analog scales (VAS), and tissue transglutaminase antibodies (tTGA) titres were evaluated. Duodenal histology and capsule endoscopy (CE) were performed when indicated. A total of 280 patients were enrolled. Thirty-two (11.4%) had a positive uGIP test (uGIP+). uGIP+ patients did not show significant differences in demographic parameters, CDAT, or VAS scores. The tTGA+ titre was not related to the positivity of uGIP (14.4% vs. 10.9% in patients with tTGA+ and tTGA-). Regarding histology, 66.7% of the GIP+ patients had atrophy compared to 32.7% of the GIP patients (p-value 0.01). However, the presence of atrophy did not correlate with tTGA. Mucosal atrophy was detected in 29 (47.5%) out of 61 patients by CE. With this method, no noticeable dependence on uGIP results (24 GIP- vs. 5 GIP+) was observed. The single uGIP test was positive in 11% of CD cases referring a correct GFD adherence. Furthermore, uGIP results significantly correlated with the duodenal biopsy, formerly considered the gold standard for assessing CD activity.