Celiakia – perspektywa socjomedyczna

Celiakia (choroba trzewna, enteropatia glutenowa) to choroba genetyczna (związana z występowaniem u chorych specyficznego wariantu genów HLA-DQ2 oraz HLA-DQ8) o charakterze autoimmunologicznym. U chorych spożywanie glutenu prowadzi do zaniku kosmków znajdujących się w błonie śluzowej dwunastnicy i jelita cienkiego, co w konsekwencji prowadzi do zaburzeń wchłaniania i innych związanych z tym dolegliwości (utrata masy ciała, anemia, niedobory witamin, osteoporoza). Jest to choroba przewlekła, nieuleczalna i w większości wypadków jedynym lekarstwem jest restrykcyjna dieta polegająca na eliminacji z pożywienia frakcji białek zawartych w takich zbożach jak pszenica (gliadyna), żyto (sekalina), jęczmień (hordeina) i owies (awenina). Celiakia to choroba najczęściej kojarzona z okresem dzieciństwa, jednak coraz częściej rozpoznawana jest w życiu dorosłym. Dieta bezglutenowa, będąca jedynym lekarstwem, wymaga od chorego systematyczności oraz konsekwencji i często wiąże się ze zmianą stylu życia. Celem artykułu jest zaprezentowanie złożoności medycznego podłoża choroby i wynikających z niego implikacji dotyczących reakcji na chorobę, życia i radzenia sobie z nią oraz społecznych i środowiskowych czynników wpływających na poprawę stanu zdrowia chorych na celiakię. Przyjęto bowiem założenie, iż jest to schorzenie wciąż mało rozpoznane w społeczeństwie, a także mało uświadomione w środowisku medycznym (o czym świadczy średni czas diagnozy celiakii). Główna teza artykułu głosi, iż celiakia jest chorobą złożoną, zaś brak klasycznego lekarstwa czyni ją schorzeniem, w którym sukces terapii zależy w ogromnym stopniu od pacjenta, jego wiedzy oraz determinacji w stosowaniu wymagającej diety eliminacyjnej. Z punktu widzenia społeczeństwa niezrozumienie chorego często negatywnie wpływa na jego zachowania w chorobie, co może prowadzić do pogorszenia stanu zdrowia. Pacjenci z celiakią borykają się dodatkowo z ograniczeniami w codziennym funkcjonowaniu – pracy, podróżach czy spotkaniach towarzyskich. Artykuł wpisuje się w ramy rozważań socjomedycznych. W pierwszej części prezentuje perspektywę medyczną dotyczącą istoty choroby, jej typów i odmian oraz diagnostyki. Prezentacja tych aspektów w pierwszej kolejności jest kluczowa dla zrozumienia istoty choroby i trudności w radzeniu sobie z nią oraz schorzeniami współwystępującymi. W drugiej części zaprezentowano – na podstawie wybranych koncepcji socjologii medycyny – chorobę z perspektywy pacjenta – jego reakcji i przyjmowania roli chorego, zachowań w chorobie, zarządzania piętnem z nią związanym, relacji z otoczeniem, a także codziennych problemów wynikających z konieczności stosowania diety eliminacyjnej. Prezentowane rozważania nie wyczerpują złożoności tematu i wieloaspektowości problematyki związanej z życiem oraz funkcjonowaniem pacjentów z celiakią. Wyodrębnione podrozdziały mają na celu ukazanie złożoności poruszanej w artykule problematyki i mogą stać się przyczynkiem do dalszych pogłębionych i szczegółowych analiz. Artykuł opiera się na przeglądzie przedmiotowej literatury polskiej i zagranicznej oraz badań w tym obszarze.

The Role of HLA Antigens and Steroid Dose on the Course of COVID-19 of Patients After Kidney Transplantation

Background: Kidney transplant recipients appear to be at higher risk for critical COVID-19. Our analysis aimed to identify the possible risk factors for a severe course of the COVID-19 disease and to determine the influence of selected human leukocyte antigens (HLAs) on the course of the disease.Methods: This is a retrospective, multicenter analysis that included patients that were confirmed to be severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive after kidney transplantation (KT). The group of patients was divided into two subgroups according to the course of the infection, as follows: non-hospitalized and hospitalized.Results: A total of 186 patients (men, 69.4%) with confirmed SARS-CoV-2 positivity were included in the group. The following independent risk factors for the outcome of hospitalization were identified: the age at the time of infection [odds ratio (OR) = 1.19, P < 0.0001], a body mass index (BMI) >29.9 kg/m2 (OR = 7.21, P < 0.0001), <7.5-mg prednisone dose/day (OR = 2.29, P = 0.0008), and HLA-DQ2 with a protective nature (OR = 0.05, P = 0.0034).Conclusions: Higher doses of corticosteroids (>7.5 mg/kg) in standard immunosuppressive regimes and HLA-DQ2 appear to be protective factors in our analysis.

The accuracy of diagnostic indicators for coeliac disease: A systematic review and meta-analysis

Background The prevalence of coeliac disease (CD) is around 1%, but diagnosis is challenged by varied presentation and non-specific symptoms and signs. This study aimed to identify diagnostic indicators that may help identify patients at a higher risk of CD in whom further testing is warranted. Methods International guidance for systematic review methods were followed and the review was registered at PROSPERO (CRD42020170766). Six databases were searched until April 2021. Studies investigating diagnostic indicators, such as symptoms or risk conditions, in people with and without CD were eligible for inclusion. Risk of bias was assessed using the QUADAS-2 tool. Summary sensitivity, specificity, and positive predictive values were estimated for each diagnostic indicator by fitting bivariate random effects meta-analyses. Findings 191 studies reporting on 26 diagnostic indicators were included in the meta-analyses. We found large variation in diagnostic accuracy estimates between studies and most studies were at high risk of bias. We found strong evidence that people with dermatitis herpetiformis, migraine, family history of CD, HLA DQ2/8 risk genotype, anaemia, type 1 diabetes, osteoporosis, or chronic liver disease are more likely than the general population to have CD. Symptoms, psoriasis, epilepsy, inflammatory bowel disease, systemic lupus erythematosus, fractures, type 2 diabetes, and multiple sclerosis showed poor diagnostic ability. A sensitivity analysis revealed a 3-fold higher risk of CD in first-degree relatives of CD patients. Conclusions Targeted testing of individuals with dermatitis herpetiformis, migraine, family history of CD, HLA DQ2/8 risk genotype, anaemia, type 1 diabetes, osteoporosis, or chronic liver disease could improve case-finding for CD, therefore expediting appropriate treatment and reducing adverse consequences. Migraine and chronic liver disease are not yet included as a risk factor in all CD guidelines, but it may be appropriate for these to be added. Future research should establish the diagnostic value of combining indicators.

Celiac Disease and Its Association with Organ-Specific Auto-Immune Diseases

Wheat is one of the most consumed foods in the world. Although it is extremely nutrient rich for us humans, some of us have great difficulties in completely digesting its protein subunits. This review aims to understand the onset of Celiac Disease and its association with several other auto-immune diseases. The gliadin molecule, undigested in the small intestine, over time, ruptures the villi lining of the intestinal wall and enters the bloodstream which in turn activates the body's immune response. In some patients with the presence of HLA DQ2/DQ8 genes, this immune response results in Celiac Disease. Notably, researchers over the past several decades have found several links between Celiac Disease and multiple auto-immune diseases. Diabetes is one such auto-immune disease which has shown multiple associations with Celiac Disease. Similarly, in this review paper, we are critically analyzing the association of Celiac Disease with some of the most common autoimmune diseases namely Type-1 Diabetes, Multiple Sclerosis, Autism and Inflammatory Bowel Disease. In this paper, we have shown a clear correlation of celiac disease with several other auto-immune diseases. Further study is needed to understand the bidirectional association of Celiac Disease with different auto-immune diseases.

Human Leukocyte Antigen (HLA) Typing Study Identifies Maternal DQ2 Susceptibility Alleles among Infertile Women: Potential Associations with Autoimmunity and Micronutrients

Background. The interplay between female fertility and autoimmune diseases (AIDs) can involve HLA haplotypes and micronutrients. We analyzed the distribution of HLA-DQ2/-DQ8 in women with infertility or recurrent spontaneous abortion (RSA) and possible associations with AIDs and micronutrient status. Methods. Consecutive women (n = 187) with infertility and RSA, and controls (n = 350) were included. All women were genotyped for HLA-DQ2 (DQA1*0201, A1*05, and B1*02) and -DQ8 (DQA1*03 and DQB1*0302) alleles. Serum 25(OH)D, VB12, folate, and ferritin were evaluated. Results. DQA1*05/B1*02 and the occurrence of at least one DQ2 allele were more prevalent among RSA and infertile women than controls. Infertile women showed lower 25(OH)D and higher prevalence of AIDs than RSA women. In the multivariate analysis, DQA1*05/B1*02 was associated with a significantly higher risk of AIDs in infertile women, and DQA1*05 was independently associated with both 25(OH)D deficiency and AIDs. In RSA women, the presence of AIDs was associated with a significantly higher risk of 25(OH)D deficiency. Conclusion. Our findings showed, for the first time, a higher proportion of DQ2 alleles in infertile and RSA women as compared to controls. Predisposing DQ2 alleles are independent risk factors for AIDs and 25(OH)D deficiency in infertile women and could represent biomarkers for performing early detection of women requiring individually tailored management.

Pro-Pre and Postbiotic in Celiac Disease

Celiac Disease (CD) is an autoimmune disease characterized by inflammation of the intestinal mucosa due to an immune response to wheat gliadins. It presents in subjects with genetic susceptibility (HLA-DQ2/DQ8 positivity and non-HLA genes) and under the influence of environmental triggers, such as viral infections and intestinal microbiota dysbiosis. The only treatment currently available in CD is a gluten-free diet for life. Despite this, the intestinal dysbiosis that is recorded in celiac subjects persists, even with adherence to dietary therapy. In this review, we have analyzed the literature over the past several decades, which have focused on the use of pro-, pre- and post-biotics in vitro and in vivo in CD. The study of probiotics and their products in CD could be interesting for observing their various effects on several different pathways, including anti-inflammatory properties.

Suspicion of celiac disease not confirmed with duodenal biopsies, now what?

Resumen Varón de 52 años en estudio por diarrea y anemia ferropénica. En endoscopia digestiva alta se observa mucosa pálida en segunda porción duodenal sin otros hallazgos de interés. Biopsias duodenales de bulbo y segunda porción muestran vellosidades sin atrofia con criptas hiperplásicas y linfocitosis intraepitelial, clasificación Marsh 2. Serología de celiaquía negativa y HLA-DQ2 positivo. Sugiere enfermedad celíaca. Se decide completar el estudio con cápsula endoscópica para confirmar el diagnóstico de sospecha. No se recomienda la videocápsula de forma rutinaria para el diagnóstico de celiaquía, pero puede ser utilizada en pacientes que rechacen endoscopia digestiva alta, con duda diagnóstica con el algoritmo habitual, como en el caso presentado, o en celiaquía refractaria a dieta estricta sin gluten. Los hallazgos más comunes compatibles con celiaquía son la reducción o ausencia de pliegues de Kerckring, fisuras de los pliegues y un patrón en mosaico con nodularidad.

SERONEGATIVE CELIAC DISEASE IN BRAZILIAN PATIENTS: A SERIES OF CASES

ABSTRACT BACKGROUND: Celiac disease (CD) is an autoimmune disease characterized by immune reaction mostly to wheat gluten. The diagnosis is based on clinical, serological and histological findings in patients ingesting gluten. Cases that the clinical profile indicates CD and the autoantibodies are negative bring so a dilemma for the professional, as the risk of missed the diagnosis or a delay at the same. OBJECTIVE: To show the importance of correct diagnosis of cases with seronegative celiac disease (SNCD). METHODS: Ten cases of SNCD Brazilian patients were retrospectively studied (2013 to 2019). Data of clinical complaints, autoantibodies, IgA serum levels, histological findings and HLA-DQ2/DQ-8 were compiled. Dual-X densitometry, delay at diagnosis, previous autoimmune diseases and family history of CD were also checked. RESULTS: All SNCD patients presented clinical symptoms of CD, with confirmed diagnosis by histological findings of the duodenal mucosa and HLA-DQ2 and/or HLA-DQ8 positivity. All patients had normal IgA levels and negative autoantibodies (IgA-anti-transglutaminase and anti-endomysial). Dual-X densitometry detected osteopenia in two women and osteoporosis in two males, all with low levels of vitamin D. Delay diagnostic ranged from 1 to 19 years. Familiar occurrence of CD was reported in 40% of the cases. After one year of gluten-free diet, eight patients refer improve of symptoms, while duodenal biopsies, done in five cases, showed histological improvement. CONCLUSION: Patients who demonstrate the clinical profile of celiac disease with negative serology and normal levels of IgA, especially those who have family members with celiac disease, should be submitted to duodenal biopsies to look for histological findings.

Interplay Between Gluten, HLA, Innate and Adaptive Immunity Orchestrates the Development of Coeliac Disease

Several environmental, genetic, and immune factors create a “perfect storm” for the development of coeliac disease: the antigen gluten, the strong association of coeliac disease with HLA, the deamidation of gluten peptides by the enzyme transglutaminase 2 (TG2) generating peptides that bind strongly to the predisposing HLA-DQ2 or HLA-DQ8 molecules, and the ensuing unrestrained T cell response. T cell immunity is at the center of the disease contributing to the inflammatory process through the loss of tolerance to gluten and the differentiation of HLA-DQ2 or HLA-DQ8-restricted anti-gluten inflammatory CD4+ T cells secreting pro-inflammatory cytokines and to the killing of intestinal epithelial cells by cytotoxic intraepithelial CD8+ lymphocytes. However, recent studies emphasize that the individual contribution of each of these cell subsets is not sufficient and that interactions between these different populations of T cells and the simultaneous activation of innate and adaptive immune pathways in distinct gut compartments are required to promote disease immunopathology. In this review, we will discuss how tissue destruction in the context of coeliac disease results from the complex interactions between gluten, HLA molecules, TG2, and multiple innate and adaptive immune components.