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Anti-SARS-CoV-2 immunoglobulin profile in patients with celiac disease living in a high incidence area.
Elli, L, Facciotti, F, Lombardo, V, Scricciolo, A, Sanders, DS, Vaira, V, Barisani, D, Vecchi, M, Costantino, A, Scaramella, L, et al
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2022;(1):3-9
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Abstract
BACKGROUND AND AIM How symptoms and antibodies related to SARS-CoV-2 infection develop in patients with celiac disease (CD) is unclear. We aimed to investigate the impact of SARS-CoV-2 infection in CD patients. METHODS CD patients were interviewed about the development of COVID-19 symptoms, compliance with anti-virus measures and adherence to a gluten-free diet (GFD). The presence of anti-SARS-CoV-2 IgG and IgA (anti-RBD and N proteins) was compared to that in non-CD subjects. Expression of the duodenal ACE2 receptor was investigated. When available, data on duodenal histology, anti-tissue transglutaminase IgA (tTGA), comorbidities and GFD adherence were analyzed. RESULTS Of 362 CD patients, 42 (12%) reported COVID-19 symptoms and 21% of these symptomatic patients presented anti-SARS-CoV-2 Ig. Overall, 18% of CD patients showed anti-SARS-CoV-2 Ig versus 25% of controls (p = 0.18). CD patients had significantly lower levels of anti-N IgA. tTGA, duodenal atrophy, GFD adherence or other comorbidities did not influence symptoms and/or antibodies. The ACE2 receptor was detected in the non-atrophic duodenal mucosa of patients; atrophy was associated with lower expression of the ACE2 receptor. CONCLUSION CD patients have an anti-SARS-CoV-2 Ig profile similar to non-celiac controls, except for anti-N IgA. No risk factors were identified among CD parameters and GFD adherence.
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Pro- and Anti- Effects of Immunoglobulin A- Producing B Cell in Tumors and Its Triggers.
Zhong, Z, Nan, K, Weng, M, Yue, Y, Zhou, W, Wang, Z, Chu, Y, Liu, R, Miao, C
Frontiers in immunology. 2021;:765044
Abstract
B cells are well known as key mediators of humoral immune responses via the production of antibodies. Immunoglobulin A (IgA) is the most abundantly produced antibody isotype and provides the first line of immune protection at mucosal surfaces. However, IgA has long been a divisive molecule with respect to tumor progression. IgA exerts anti- or pro-tumor effect in different tumor types. In this review, we summarize emerging evidence regarding the production and effects of IgA and IgA+ cells in the tumor microenvironment (TME). Moreover, we discuss that the TME cytokines, host diet, microbiome, and metabolites play a pivotal role in controlling the class-switch recombination (CSR) of IgA. The analysis of intratumoral Ig repertoires and determination of metabolites that influence CSR may help establish novel therapeutic targets for the treatment of cancers.
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Tracking of low disease burden in multiple myeloma: Using mass spectrometry assays in peripheral blood.
Chapman, JR, Thoren, KL
Best practice & research. Clinical haematology. 2020;(1):101142
Abstract
Efforts over the last 5 years have demonstrated that it is technically feasible to detect low levels of monoclonal proteins in peripheral blood using mass spectrometry. These methods are based on the fact that an M-protein has a specific amino acid sequence, and therefore, a specific mass. This mass can be tracked over time and can serve as a surrogate marker of the presence of clonal plasma cells. This review describes the use of mass spectrometry to detect M-proteins in multiple myeloma to date, identifies the challenges of using this biomarker, and describes potential strategies to overcome these challenges. We discuss the work that must be done for these techniques to be incorporated into clinical practice for tracking of low disease burden in multiple myeloma.
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Serum IL-21 levels from celiac disease patients correlates with anti-tTG IgA autoantibodies and mucosal damage.
Iervasi, E, Auricchio, R, Strangio, A, Greco, L, Saverino, D
Autoimmunity. 2020;(4):225-230
Abstract
Objectives: Coeliac disease is a multifactorial disorder influenced by environmental, genetic and immunological factors. Interleukin (IL)-21 has been linked to an increase disease risk and the serum level of IL-21 seems to be increased in CD compared to a healthy control population.Methods: Sera were collected from 160 CD patients, 120 untreated and 40 following a gluten-free diet, and form 45 healthy subjects. Serum IL-21 was evaluated by specific ELISA tests.Results: Our data show that patients with untreated CD display IL-21 concentrations significantly higher than both treated-CD patients (following a gluten-free diet) and controls. In addition, serum IL-21 correlates with serum titres of anti-tTG IgA autoantibodies. Finally, our results show a correlation of this cytokine with duodenal mucosal damage.Conclusions: A role of gluten, as antigen with stimulatory function on IL-21 production, seems to be confirmed by the longitudinal analyses showing that the gluten-free diet decreases to a nearly undetectable amount this cytokine. In addition, the finding of a positive correlation between the serum amount of IL-21 and the grade of duodenal mucosa damage suggests a strong immunomodulatory effect of this cytokine on cytotoxic T lymphocyte functions. This study provides an extra evidence to emerging data on the potential role IL-21 in CD pathogenesis, suggesting its involvement in the development and progression of CD. Significance statement: In untreated CD, serum IL-21 shows higher levels compared with treated CD and healthy subjects. Serum amounts of IL-21 correlate with anti-tTG IgA autoantibodies and with duodenal mucosa damage.
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Rapid Detection of Femtogram Amounts of Protein by Gel-Free Immunoblot.
Shlyapnikov, YM, Malakhova, EA, Shlyapnikova, EA
Bulletin of experimental biology and medicine. 2020;(6):840-843
Abstract
The article presents a new method of immunoblotting for simple, rapid, and highly sensitive detection of proteins. Electrophoretic separation of sample is carried out under non-denaturing conditions in a thin conductive layer between cellulose membranes without polyacrylamide gel. The membrane surface is preliminarily modified with azidophenyl groups to photochemically immobilize proteins in situ. For visualization of protein bands, the membranes are treated with magnetic beads coated with specific antibodies, unbound particles are then removed with a magnet. The detection limit in the model system with biotinylated BSA and magnetic beads coated with streptavidin reaches 10 fg or about 105 molecules, while the total blotting time does not exceed 5 min. The method was applied for detection of IgA in a sample of human exhaled air. The method can be used for the analysis of various complex biological samples containing low amounts of the analyte.
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Relationship between serum levels of immunoglobulins and metabolic syndrome in an adult population: A population study from the TCLSIH cohort study.
Wang, X, Fu, J, Gu, Y, Chi, VTQ, Zhang, Q, Liu, L, Meng, G, Yao, Z, Wu, H, Bao, X, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2019;(9):916-922
Abstract
BACKGROUND AND AIMS Metabolic syndrome (MetS) is a combination of metabolic disorders that increase the risk of developing cardiovascular disease, and inflammation is considered as a pathological basis for MetS. Immunoglobulins (Igs) are the major secretory products of the adaptive immune system. However, no large-scale population study has focused on a possible relationship between Igs and MetS. We designed a cross-sectional study to investigate the relationship between Igs and prevalence of MetS in a large-scale adult population. METHODS AND RESULTS A total of 10,289 participants were recruited among residents in Tianjin, China. Metabolic syndrome was defined in accordance with the criteria of the American Heart Association scientific statements of 2009. Serum levels of Igs were determined by immunonephelometry. Multiple logistic regression models were used to assess the relationship between the quintiles of serum levels of Igs and the prevalence of MetS. The overall prevalence of MetS was 36.1%. The mean (standard deviation) values of Igs (IgG, IgE, IgM, and IgA) were 1205.7 (249.3) mg/dL, 93.1 (238.9) IU/mL, 105.7 (57.3) mg/dL, and 236.2 (97.6) mg/dL, respectively. The adjusted odds ratios (95% confidence interval) of MetS for the highest quintile of Igs (IgG, IgE, IgM, and IgA), when compared to the lowest quintile, were 0.81 (0.70, 0.95), 0.97 (0.83, 1.12), 1.13 (0.97, 1.33), and 1.52 (1.30, 1.77), respectively. CONCLUSIONS This study demonstrated that decreased IgG and increased IgA are independently related to a higher prevalence of MetS. The results indicate that the Igs might be useful predictive factors for MetS in the general adult population.
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AGA Clinical Practice Update on Diagnosis and Monitoring of Celiac Disease-Changing Utility of Serology and Histologic Measures: Expert Review.
Husby, S, Murray, JA, Katzka, DA
Gastroenterology. 2019;(4):885-889
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Abstract
PURPOSE The purpose of this clinical practice update is to define key modalities in the diagnosis and monitoring of celiac disease (CD) in adults as well as in children and adolescents. METHODS The recommendations outlined in this expert review are based on available published evidence, including cohort and case-control studies of the diagnostic process as well as controlled and descriptive studies of disease management. Best Practice Advice 1: Serology is a crucial component of the detection and diagnosis of CD, particularly tissue transglutaminase-immunoglobulin A (TG2-IgA), IgA testing, and less frequently, endomysial IgA testing. Best Practice Advice 2: Thorough histological analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry is important for diagnosis as well as for differential diagnosis. Best Practice Advice 2a: TG2-IgA, at high levels (> ×10 upper normal limit) is a reliable and accurate test for diagnosing active CD. When such a strongly positive TG2-IgA is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for CD is virtually 100%. In adults, esophagogastroduodenoscopy (EGD) and duodenal biopsies may then be performed for purposes of differential diagnosis. Best Practice Advice 3: IgA deficiency is an infrequent but important explanation for why patients with CD may be negative on IgA isotype testing despite strong suspicion. Measuring total IgA levels, IgG deamidated gliadin antibody tests, and TG2-IgG testing in that circumstance is recommended. Best Practice Advice 4: IgG isotype testing for TG2 antibody is not specific in the absence of IgA deficiency. Best Practice Advice 5: In patients found to have CD first by intestinal biopsies, celiac-specific serology should be undertaken as a confirmatory test before initiation of a gluten-free diet (GFD). Best Practice Advice 6: In patients in whom CD is strongly suspected in the face of negative biopsies, TG2-IgA should still be performed and, if positive, repeat biopsies might be considered either at that time or sometime in the future. Best Practice Advice 7: Reduction or avoidance of gluten before diagnostic testing is discouraged, as it may reduce the sensitivity of both serology and biopsy testing. Best Practice Advice 8: When patients have already started on a GFD before diagnosis, we suggest that the patient go back on a normal diet with 3 slices of wheat bread daily preferably for 1 to 3 months before repeat determination of TG2-IgA. Best Practice Advice 9: Determination of HLA-DQ2/DQ8 has a limited role in the diagnosis of CD. Its value is largely related to its negative predictive value to rule out CD in patients who are seronegative in the face of histologic changes, in patients who did not have serologic confirmation at the time of diagnosis, and in those patients with a historic diagnosis of CD; especially as very young children before the introduction of celiac-specific serology. MANAGEMENT Best Practice Advice 10: Celiac serology has a guarded role in the detection of continued intestinal injury, in particular as to sensitivity, as negative serology in a treated patient does not guarantee that the intestinal mucosa has healed. Persistently positive serology usually indicates ongoing intestinal damage and gluten exposure. Follow-up serology should be performed 6 and 12 months after diagnosis, and yearly thereafter. Best Practice Advice 11: Patients with persistent or relapsing symptoms, without other obvious explanations for those symptoms, should undergo endoscopic biopsies to determine healing even in the presence of negative TG2-IgA.
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IgA anti-tissue transglutaminase antibodies and IgG antibodies against deamidated gliadin peptides as predictors of celiac disease.
Ortiz, G, Messere, G, Toca, MDC, Fiorucci, M, Bigliardi, R, Vidal, J, Reynoso, R
Archivos argentinos de pediatria. 2019;(1):52-55
Abstract
OBJECTIVE To compare the performance of IgA anti-tissue transglutaminase antibodies (IgA anti-tTG), IgA anti-endomysial antibodies (IgA EMA), and IgA/IgG antibodies against deamidated gliadin peptides (IgA/IgG anti-DGP) for the diagnosis of celiac disease. METHODS Descriptive study in patients with celiac disease. Anti-DGP (IgA/IgG), IgA EMA, IgA anti-tTG antibodies were measured and an intestinal biopsy was done. Sex: female (61 %). Median age: 78.4 months old. RESULTS A total of 136 children were included; 108 had high IgA anti-DGP titers; 124, increased IgG anti-DGP titers; 128, positive IgA EMA titers; and 130, increased IgA anti-tTG titers. High IgG anti-DGP titers were observed in 4/6 patients with negative IgA anti-tTG antibodies. The combination of IgG anti-DGP + IgA anti-tTG antibodies showed a positive correlation in 134 patients and the IgG anti-DGP + EMA combination was positive in 133 children. CONCLUSION IgA EMA, IgA anti-tTG, and IgG anti-DGP antibodies exhibited an adequate specificity and sensitivity. The IgG anti-DGP/anti-tTG combination showed a 98-99 % sensitivity and a 100 % specificity. The anti-tTG and IgG anti-DGP option yields excellent results, with a low cost and independence from the observer.
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Single strain versus multispecies probiotic on necrotizing enterocolitis and faecal IgA levels in very low birth weight preterm neonates: A randomized clinical trial.
Gómez-Rodríguez, G, Amador-Licona, N, Daza-Benítez, L, Barbosa-Sabanero, G, Carballo-Magdaleno, D, Aguilar-Padilla, R, González-Ramirez, E
Pediatrics and neonatology. 2019;(5):564-569
Abstract
BACKGROUND According to the literature, probiotics are an attractive alternative to prevent necrotizing enterocolitis (NEC). However, due to differences in probiotic composition, randomized controlled trials are necessary to compare different probiotic mixtures. The objective of this study was to compare single strain (Lactobacillus acidophilus boucardii) versus multispecies probiotics on NEC incidence and faecal secretory Immunoglobulin A (sIgA) levels in very low preterm newborns. METHODS We performed a double-blind randomized trial in 90 newborns. L. acidophilus boucardii strain or multispecies probiotics were randomly assigned to preterm newborns. As the primary outcome, we evaluated NEC incidence on the total length of neonatal intensive care unit (NICU) stay. As the secondary outcome, we measured the change in faecal sIgA levels from baseline to 3 weeks following the use of probiotics. RESULTS NEC incidence was similar between groups (0% vs. 2.2% for the single strain and multispecies probiotic, respectively). Faecal sIgA levels increased significantly (p < 0.001) within groups (31% for single strain and 47% for multispecies probiotic), but this increase was not different between groups. Neonates with a faecal sIgA level increment >0.45 mg/dl showed higher gestational age, birth weight, and weight at the second and third weeks of follow up than neonates with a faecal sIgA level increment ≤0.45 mg/dl. No adverse effects were found after probiotics use. CONCLUSIONS No difference between strains of probiotics used was found on NEC incidence or in the increase of faecal sIgA levels. Faecal sIgA levels were positively related to gestational age and body weight in very low preterm infants. ClinicalTrials.gov/NCT02245815.
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A New Vision of IgA Nephropathy: The Missing Link.
Sallustio, F, Curci, C, Di Leo, V, Gallone, A, Pesce, F, Gesualdo, L
International journal of molecular sciences. 2019;(1)
Abstract
IgA Nephropathy (IgAN) is a primary glomerulonephritis problem worldwide that develops mainly in the 2nd and 3rd decade of life and reaches end-stage kidney disease after 20 years from the biopsy-proven diagnosis, implying a great socio-economic burden. IgAN may occur in a sporadic or familial form. Studies on familial IgAN have shown that 66% of asymptomatic relatives carry immunological defects such as high IgA serum levels, abnormal spontaneous in vitro production of IgA from peripheral blood mononuclear cells (PBMCs), high serum levels of aberrantly glycosylated IgA1, and an altered PBMC cytokine production profile. Recent findings led us to focus our attention on a new perspective to study the pathogenesis of this disease, and new studies showed the involvement of factors driven by environment, lifestyle or diet that could affect the disease. In this review, we describe the results of studies carried out in IgAN patients derived from genomic and epigenomic studies. Moreover, we discuss the role of the microbiome in the disease. Finally, we suggest a new vision to consider IgA Nephropathy as a disease that is not disconnected from the environment in which we live but influenced, in addition to the genetic background, also by other environmental and behavioral factors that could be useful for developing precision nephrology and personalized therapy.