Total IgA Levels Research Articles

Prevalence of celiac disease-specific antibodies and their association with clinical status and environmental factors

Background and aimsCeliac disease (CeD) affects 1–2% of the world's population. The aim of this study was to relate the incidence of CeD-related serological markers to symptoms, pathologies, and environmental exposure to wheat flour, given the number of flour mills present in the region. Materials & methodsSerum samples were collected from 537 inhabitants from a rural city. Levels of anti-transglutaminase (a-tTg), anti-gliadin, anti-DGP antibodies and total IgA levels were measured. Volunteers completed a questionnaire covering environmental factors, demographics, pregnancies, other diseases, symptoms, and CeD diagnosis. Geo-referencing of volunteers' homes and mills in the city was performed, and correlations between the different parameters assessed were analysed. ResultsA CeD incidence of 1.76 % was found. However, a-tTg and a-gliadin levels were elevated in the population without CeD diagnosis (9.6 % and 30.1 %). Subjects with CD diagnosis showed diarrhoea and colic pain. Women with CeD had fewer pregnancies. Positive a-tTg and number of CeD-associated symptoms appear to correlate with proximity to flour mills. ConclusionA high prevalence of CeD-related specific antibody positivity in a rural population was found, possibly due to environmental factors related to flour mills. Further research is needed to better understand CeD's pathogenesis and its health implications.

Patients With Immunoglobulin A Nephropathy Show Abnormal Frequencies of B Cell Subsets, Unconventional T Cells, and High Levels of Galactose-Deficient IgA1–Coated Gut Bacteria

BackgroundMucosal inflammation is involved in the pathophysiology of Immunoglobulin-A nephropathy (IgAN), but peripheral immune phenotype analyses of IgAN patients often do not include unconventional T cells, the major subset in mucosal immunity. MethodsWe measured serum total IgA, gd-IgA1, secretory IgA, B cell activating factor (BAFF), and A proliferation-inducing ligand (APRIL) in 66 IgAN patients and 30 healthy controls (HC). We also quantified total IgA and gd-IgA1 in stool supernatant and coated on bacteria. In 35 patients and 14 controls, we performed extensive phenotyping (CyTOF) of circulating immune cells, including unconventional T cells [mucosal associated invariant T (MAIT) cells, γδ T, and NK T cells]. The results were validated using RNAseq data from a larger cohort of 179 patients with IgAN, 140 patients with minimal change disease (MCD), and 91 HC. ResultsIgAN patients had higher circulating levels of total IgA, gd-IgA1, and APRIL and higher IgA- and gd-IgA1-coated gut bacteria than controls, while serum levels of secretory IgA and BAFF did not differ between groups. IgAN patients showed more class switched memory and double negative B cells than controls. MAIT cells and γδ T cells were significantly lower, and CD4- CD8- NK T cells significantly higher in IgAN patients than in HC. We validated the significant decrease in MAIT cells in an independent cohort of patients with IgAN. ConclusionThe data indicate that patients with IgAN have increased circulating class switched memory and double negative B cells associated with abnormal T cell immunity, involving defects in unconventional T cell frequency. This may suggest putative alterations at mucosal sites due to cell migration leading to altered IgA production.

Exploring Total Immunoglobulin A's Impact on Non-Biopsy Diagnosis of Celiac Disease: Implications for Diagnostic Accuracy.

In the current debate surrounding the biopsy-free diagnosis of CeD, it is crucial to identify factors influencing the accuracy of results. This study investigated the impact of total IgA on the non-invasive diagnosis of celiac disease (CeD). We retrospectively assessed total IgA titers' influence on the diagnostic accuracy of different tTG-IgA thresholds compared to the upper reference value (UNL). Of 165 included patients, tTG-IgA values at 10× UNL and 6× UNL showed specificity of 82.6% and 73.9% and sensitivity of 49.3% and 69.0%, respectively, in predicting intestinal villous atrophy (Marsh 3). In 130 patients, total IgA levels were known at baseline. These patients were divided into three tertiles according to total IgA, i.e., patients with lower, intermediate, or higher total IgA within the population. For patients with total IgA ≥ 245 mg/dL, using a tTG-IgA cutoff of 6× UNL instead of 10× UNL resulted in decreased specificity from 71.4% to 42.8% and increased sensitivity from 67.6% to 81.1%. For patients with total IgA < 174 mg/dL and between 174 mg/dL and 245 mg/dL, using a tTG-IgA cutoff of 6× UNL instead of 10× UNL maintained specificity (75.0% and 85.7%, respectively) with increased sensitivity (from 46.2% to 64.1% and from 36.1% to 52.8%, respectively). In conclusion, total IgA influences the diagnostic accuracy of a predetermined tTG-IgA cutoff. Greater consideration should be given to total IgA, beyond its deficiency, in evaluating the applicability and accuracy of non-invasive CeD diagnosis.

Dynamic features of the humoral immunity in patients with acute coronary syndrome depending on the content of B lymphocytes with the CD3&lt;sup&gt;-&lt;/sup&gt;CD19&lt;sup&gt;+&lt;/sup&gt;CD5&lt;sup&gt;+&lt;/sup&gt; phenotype, who have and have not COVID-19

The purpose of the work was to study the dynamic features of the humoral immunity in patients with acute coronary syndrome depending on the content of B lymphocytes with the CD3-CD19+CD5+ phenotype, who had and did not have COVID-19. We analyzed data on humoral immunity in men aged 40 to 65 years with acute coronary syndrome, who had and did not have COVID-19, depending on the content of B lymphocytes with the CD3-CD19+CD5+ phenotype. All patients underwent coronary angiography with further stenting of the coronary arteries. The values of lymphocytes with the CD45+CD3-CD19+ phenotype and the presence or absence of COVID-19 previously were taken into account. Using the flow cytometry method, 2 groups were gated using the pan-leukocyte marker CD45+: the subgroup of B lymphocytes CD3-CD19+CD5+ and the subgroup of B lymphocytes CD3-CD19+CD5-, B lymphocytes (CD45+CD3-CD19+). Levels of total IgA, IgG, IgM, C1-inhibitor, C3a and C5a complement components by enzyme immunoassay. After coronary artery stenting, B lymphocytes (CD3-CD19+CD5+) significantly increased in the group of people with COVID-19, with initially low levels of these cells (p 0.01) and normal cells (p 0.05). In individuals who had COVID-19 and did not have this disease, with initially decreased CD3-CD19+CD5+ cells, B lymphocytes (CD45) increased significantly (p 0.001 and p 0.05, respectively) over time (p 0.05+CD3-CD19+), B lymphocytes (CD3-CD19+CD5-). In the group of patients who recovered from COVID-19 with normal CD3-CD19+CD5+ cells, the relative number of B-lymphocytes decreased over time (p 0.01) (CD45+CD3-CD19+) and CD3-CD19+CD5- cells. In persons who had previously suffered from COVID-19, with increased CD3-CD19+CD5+ cells, the number of B-lymphocytes (CD45+) significantly (p 0.05) decreased over time CD3-CD19+), in those who did not have COVID-19 with high above-mentioned cells, immunoglobulin A significantly (p 0.05) increased. The most severe clinically was the group of people with low CD3-CD19+CD5+B cells and COVID-19 in the anamnesis.

Genetic, Clinical, Epidemiological, and Immunological Profiling of IgG Response Duration after SARS-CoV-2 Infection.

The IgG response against SARS-CoV-2 infection can persist for over six months (long response; LR). However, among 30% of those infected, the duration can be as short as three months or less (short response; SR). The present study assembled serological data on the anti-SARS-CoV-2 IgG response duration of two previous studies and integrated these results with the plasmatic cytokine levels and genetic profile of 10 immune-relevant SNPs that were also previously published, along with the plasmatic total IgG, IgA, and IgM levels, allowing for the genetic, clinical, immunological, and epidemiological aspects of the post-COVID-19 IgG response duration to be understood. The SR was associated with previous mild acute COVID-19 and with an SNP (rs2228145) in IL6R related to low gene expression. Additionally, among the SR subgroup, no statistically significant Spearman correlations were observed between the plasma levels of IL-17A and the Th17 regulatory cytokines IFN-γ (rs = 0.2399; p = 0.1043), IL-4 (rs = 0.0273; p = 0.8554), and IL-2 (rs = 0.2204; p = 0.1365), while among the LR subgroup, weaker but statistically significant Spearman correlations were observed between the plasma levels of IL-17A and IFN-γ (rs = 0.3873; p = 0.0016), IL-4 (rs = 0.2671; p = 0.0328), and IL-2 (rs = 0.3959; p = 0.0012). These results suggest that the Th17 response mediated by the IL-6 pathway has a role in the prolonged IgG response to SARS-CoV-2 infection.

Okinawa-Based Nordic Diet Decreases Plasma Levels of IAPP and IgA against IAPP Oligomers in Type 2 Diabetes Patients.

Pancreas-derived islet amyloid polypeptide (IAPP) aggregates and deposits in the pancreas and periphery of Type 2 Diabetes (T2D) patients, contributing to diabetic complications. The excess IAPP can be removed by autoantibodies, and increased levels of immunoglobulin (Ig) G against IAPP have been reported in T2D patients. However, whether other Ig classes are also affected and if the levels can be managed is less known. This pre-post study examines IgA levels against IAPP oligomers (IAPPO-IgA) in T2D patients and assesses the impact of the Okinawa-based Nordic (O-BN) diet-a low-carbohydrate, high-fiber diet-on these levels after following the diet for 3 months. IAPP, IAPPO-IgA, and total IgA levels were measured in plasma and fecal samples from n = 30 T2D patients collected at baseline, after 3 months of diet, and after additional 4 months of unrestricted diets (a clinical follow-up). The IAPP and IAPPO-IgA levels were significantly lower after 3 months, with the latter also being significantly reduced at the clinical follow-up. The reduction in plasma IAPP and IAPPO-IgA levels correlated with reductions in plasma levels of metabolic and inflammatory markers. Hence, following the O-BN diet for at least 3 months is sufficient to reduce circulating IAPP and IAPPO-IgA levels, which may be principal in managing T2D.

Association of HLA-DQ4/5 genotype polymorphisms with celiac disease in a group of children in Southwest Iran: A case-control study.

Celiac disease (CD) has proinflammatory and pathogenic immune responses to gluten in intestinal tissue, leading to structural changes in the mucosa of the small intestine. The association of human leukocyte antigen (HLA)-DQ2 and DQ8 genotypes with CD has been previously reported. This test has a negative predictive value close to 100%, so its main purpose is to rule out the detection of CD completely or almost completely. There is limited information regarding HLA-DQ4/5 in CD. This study was conducted to determine the HLA-DQ4/5 genotypes in a group of Southwestern Iranian children with CD. We conducted a case-control study in Southwest Iran involving 100 participants, employing a nonprobabilistic sampling method. Samples were taken from participants' oral buccal mucosa at Imam Sajjad Hospital of Yasuj, Iran. Then DNA was extracted from these samples and used to determine the frequency of HLA-DQ4/5 genotypes through Sequence-Specific Primer-Polymerase Chain Reaction assay. SPSS 20 was utilized for statistical analyses. Fifty diagnosed patients with CD (high anti-tissue transglutaminase [tTG]-IgA level [upper limit of normal] with pathological findings of Marsh III) and 50 non-CD individuals (normal anti-tTG-IgA level and normal total IgA level) were enrolled in the study from August 5, 2022 to October 15, 2023. Findings showed that the DQ4a*4b allele has the highest frequency in the CD samples (78%, p < 0.01) followed by the DQ5a*5b allele (12%, p < 0.01). Additionally, there was a higher prevalence of DQ4/DQ5 in patients with CD compared to controls (odds ratio = 6.5, confidence interval = 0.84 to 69.46, p < 0.01). Furthermore, a significant association was found among HLA DQ4/5 genotype, age (>9.5) (p < 0.01), and gender (female) (p < 0.05). The observed significant differences among HLA-DQ4 and HLA-DQ5 in Iranian CD samples against controls and the high value of the relative risks showed the significant function of the studied alleles in the prevalence of CD in Iranian patients.

Immunoadsorption and Plasma Exchange are Comparable in Anti-Neutrophil Cytoplasmic Antibodies or Anti-Glomerular Basement Membrane Removal Kinetics

IntroductionApheresis allows the fast removal of auto-antibodies in anti-glomerular basement membrane (GBM) disease, and in severe ANCA-associated vasculitis. The CINEVAS study tested whether immunoadsorption (IA) allowed a faster removal of ANCA and/or anti-GBM antibodies than plasma exchanges (PEx). MethodsCINEVAS was a prospective multicenter study comparing IA to PEx in consecutive patients with ANCA and/or anti-GBM vasculitides. The primary objective was the reduction rate in auto-antibody titers between the beginning of the first and the end of the seventh apheresis session. Secondary objectives were: number of sessions needed to obtain desired reduction rates; reduction rates of total immunoglobulin (Ig) levels; tolerance of sessions; and patients’ outcome. ResultsThe results of 38 patients (16 treated with IA and 22 with PEx), and 43 auto-antibodies, were analyzed. There was no difference in the reduction rates in auto-antibody titers over 7 sessions between IA and PEx (respectively 98% vs 96%, p=0.39). The numbers of sessions needed to obtain undetectable auto-antibodies, or 50%, 75% or 90% reductions, did not differ between techniques. Greater reduction rates of auto-antibodies were observed when plasma was separated by filtration compared to centrifugation, with IA and PEx. IA allowed a greater reduction in total IgG levels, and better preservation of total IgA and IgM levels than PEx. PEx sessions required higher volumes of plasma, IA sessions higher volumes of citrate; IA sessions were longer. ConclusionsImmunoadsorption and plasma exchange were comparable in ANCA or anti-GBM removal kinetics, despite a faster reduction in total IgG with IA.

Natural antibodies targeting LPS in pleural effusions of various etiologies.

Respiratory infection, cancer, and heart failure can cause abnormal accumulation of fluid in the pleural cavity. The immune responses within the cavity are orchestrated by leucocytes that reside in the serosal-associated lymphoid tissue. Natural antibodies (NAbs) are abundant in the serum (S) having a major role in systemic and mucosal immunity; however, their occurrence in pleural fluid (PF) remains an open question. Our aim herein was to detect and measure the levels of NAbs (IgM, IgG, IgA) targeting lipopolysaccharides (LPS) in both the pleural fluid and the serum of 78 patients with pleural effusions (PEs) of various etiologies. The values of anti-LPS NAb activity were extracted through a normalization step regarding the total IgM, IgG, and IgA levels, all determined by in-house ELISA. In addition, the ratios of PF/S values were analyzed further with other critical biochemical parameters from pleural fluids. Anti-LPS NAbs of all Ig classes were detected in most of the samples, while a significant increase of anti-LPS activity was observed in infectious and noninfectious compared with malignant PEs. Multivariate linear regression confirmed a negative correlation of IgM and IgA anti-LPS PF/S ratio with malignancy. Moreover, anti-LPS NAbs PF/S measurements led to increased positive and negative predictive power in ROC curves generated for the discrimination between benign and malignant PEs. Our results highlight the role of anti-LPS NAbs in the pleural cavity and demonstrate the potential translational impact that should be further explored.NEW & NOTEWORTHY Here we describe the detection and quantification of natural antibodies (NAbs) in the human pleural cavity. We show for the first time that IgM, IgG, and IgA anti-LPS natural antibodies are detected and measured in pleural effusions of infectious, noninfectious, and malignant etiologies and provide clinical correlates to demonstrate the translational impact of our findings.

Exhaled Nitric Oxide Reflects the Immune Reactions of the Airways in Early Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide antibodies (ACPAs), specified as cyclic citrullinated peptide 2 (CCP2), were included. Their exhaled NO levels were measured, and the alveolar concentration, the airway compartment diffusing capacity and the airway wall concentration of NO were estimated using the Högman-Meriläinen algorithm. The disease activity was measured using the Disease Activity Score for 28 joints. Serum samples were analysed for anti-CCP2, rheumatoid factor, free secretory component, secretory component containing ACPAs, antibodies against Porphyromonas gingivalis (Rgp) and total levels of IgA, IgA1 and IgA2. Significant negative correlations were found between the airway wall concentration of NO and the number of swollen joints (Rho -0.48, p = 0.004), between the airway wall concentration of NO and IgA rheumatoid factor (Rho -0.41, p = 0.017), between the alveolar concentration and free secretory component (Rho -0.35, p = 0.023) and between the alveolar concentration and C-reactive protein (Rho -0.36, p = 0.016), but none were found for anti-CCP2, IgM rheumatoid factor or the anti-Rgp levels. In conclusion, altered NO levels, particularly its production in the airway walls, may have a role in the pathogenesis of ACPA-positive RA.

Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination

There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response. To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection. In this cohort study, SARS-CoV-2-naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France. Data were analyzed from October 25, 2022, to July 13, 2023. An ultrasensitive digital enzyme-linked immunosorbent assay was used for the comparison of SARS-CoV-2 spike-specific serum and salivary IgG and IgA levels. Spike-specific secretory IgA level was also quantified at selected times. A total of 427 individuals were included in 3 groups: participants with SARS-CoV-2 prior to vaccination who received 1 single dose of BNT162b2 (Pfizer-BioNTech) (n = 120) and SARS-CoV-2-naive individuals who received 2 doses of mRNA-1273 (Moderna) (n = 172) or 2 doses of BNT162b2 (Pfizer-BioNTech) (n = 135). The median age was 68 (IQR, 39-75) years, and 228 (53.4%) were men. SARS-CoV-2 spike-specific IgG saliva levels increased after 1 or 2 vaccine injections in individuals with previous infection and SARS-CoV-2-naive individuals. After vaccination, SARS-CoV-2-specific saliva IgA levels, normalized with respect to total IgA levels, were significantly higher in participants with previous infection, as compared with the most responsive mRNA-1273 (Moderna) recipients (median normalized levels, 155 × 10-5 vs 37 × 10-5 at day 29; 107 × 10-5 vs 54 × 10-5 at day 57; and 104 × 10-5 vs 70 × 10-5 at day 180 [P < .001]). In contrast, compared with day 1, spike-specific IgA levels in the BNT162b2-vaccinated SARS-CoV-2-naive group increased only at day 57 (36 × 10-5 vs 49 × 10-5 [P = .01]). Bona fide multimeric secretory IgA levels were significantly higher in individuals with previous infection compared with SARS-CoV-2-naive individuals after 2 antigenic stimulations (median optical density, 0.36 [IQR, 0.16-0.63] vs 0.16 [IQR, 0.10-0.22]; P < .001). The findings of this cohort study suggest that mRNA vaccination was associated with mucosal immunity in individuals without prior SARS-CoV-2 infection, but at much lower levels than in previously infected individuals. Further studies are needed to determine the association between specific saliva IgA levels and prevention of infection or transmission.

Gravity-driven crossflow membrane filtration and mechanical centrifugation yield plasma with equivalent total and COVID-19-specific immunoglobulin content

While the administration of convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), upfront costs and technological barriers of conventional plasmapheresis have limited the collection and processing of COVID-19 convalescent plasma (CCP) in Low- and Middle-Income Countries (LMICs). We previously reported that bedside plasma separation using gravity-driven microfiltration has made CCP therapy accessible as a treatment option in Suriname. However, the question remains whether the gravity-driven microfiltration method yields similar amounts of immunoglobulins as compared to conventional plasmapheresis. Here, we compared the gravity-driven microfiltration method with conventional plasma centrifugation for the total and COVID-19-specific immunoglobulin content of the obtained CCP. Blood donations from 10 donors recovered from PCR-confirmed COVID-19 were processed using both methods. Samples were collected pre- and post-processing for analysis to allow direct comparison of both methods. There were no differences in COVID-19-specific IgG levels between convalescent plasma obtained by microfiltration and centrifugation for 4 of the 5 assays used. Anti-RBD-Omicron IgG levels were slightly higher in the plasma obtained after filtration (median 274, range 69 to 1258) than after centrifugation (median 249, range 67 to 1175), Wilcoxon P = 0.0488. No significant differences were detected between the two methods for levels of total albumin, total cholesterol, total IgA, IgM and IgG levels. These results indicate that gravity-driven microfiltration and conventional centrifugation yield CCP with equivalent amounts of total and COVID-19-specific antibodies. This makes the gravity-driven microfiltration method a viable option for the collection and treatment with CCP in the LMICs setting.

Evaluation of Frequency of Celiac Disease in Children with Idiopathic Epilepsy.

Extra gastrointestinal symptoms in celiac disease (CD), such as neurological manifestations, might be common in pediatrics. The present study aimed to evaluate the frequency of CD in children with idiopathic epilepsy. In a cross-sectional study, signs and symptoms of CD were evaluated in 40 children aged 2-14 years with idiopathic epilepsy who were referred to the Pediatric Neurology Clinic of Shahid Sadoughi Medical Sciences University, Yazd, Iran. Then, serum levels of tissue transglutaminase antibody (tTG) and total IgA were measured in them. Upper gastrointestinal endoscopy and small intestine biopsy were recommended for patients with abnormal serum IgA Anti-tTG. Eighteen girls and 22 boys with a mean age of 5.29±2.4 years were evaluated. In this study, only three patients (7.5%) with epilepsy had abnormal serum IgA Anti-tTG and serum Total IgA. Upper gastrointestinal endoscopy and pathological examination of duodenal biopsy of those three children reported total villous atrophy (Marsh type 3). The age of onset of seizures in children with CD was more than three years, while in children without CD, 62.2% of cases were less than three years. These results indicate that CD is associated with the age of onset of seizures in children. Due to the accompaniment of celiac with neurological manifestations, patients with neurological symptoms and gastrointestinal symptoms should be examined for celiac.

Impact of RYGB surgery on plasma immunoglobulins: association between blood pressure and glucose levels six months after surgery.

We aimed to study levels of natural antibodies in plasma, and their associations to clinical and fecal biomarkers, before and 6 months after Roux-en-Y gastric bypass (RYGB) surgery. Thirty individuals with obesity [16 type 2 diabetic, 14 non-diabetic (ND)] had RYGB surgery. Total plasma IgA, IgG and IgM antibody levels and specific antibodies to oxidized low-density lipoprotein (oxLDL), malondialdehyde-acetaldehyde adducts, Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44), and phosphocholine were measured using chemiluminescence immunoassay. Associations between plasma and fecal antibodies as well as clinical markers were analyzed. RYGB surgery reduced blood pressure, and the glycemic state was improved. A higher level of diastolic blood pressure was associated with lower plasma antibodies to oxLDL after surgery. Also, lower level of glucose markers associated with lower level of plasma antibodies to bacterial virulence factors. Antibodies to oxLDL decreased after surgery, and positive association between active serum lipopolysaccharide and specific oxLDL antibodies was detected. Total IgG levels decreased after surgery, but only in ND individuals. Reduced level of total plasma IgG, improved state of hypertension and hyperglycemia and their associations with decreased levels of specific antibodies in plasma, suggest an improved state of systemic inflammation after RYGB surgery.

Abstract 11949: Novel First-Trimester Serum Biomarkers for Early Prediction of Preeclampsia

Background: Preeclampsia (PE) is a leading cause of maternal and perinatal mortality and morbidity worldwide, but effective early prediction remains a challenge due to the lack of reliable biomarkers. Research questions: Could potential imbalances in cytokines and autoimmune antibodies be detectable in the first trimester of pregnancy in women who later develop PE? Goals: Our study aims to discover novel biomarkers within the first trimester and construct an efficient predictive model to enhance early PE screening strategies. Methods: Based on the extensive human biobank of our large-scale assisted reproductive cohort platform, we measured the first-trimester serum levels of 48 cytokines, total immunoglobulins (Igs), anti-phosphatidylserine (aPS) antibodies, and several previously identified PE biomarkers—including placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and activin A—in 34 women diagnosed with PE and 34 matched normotensive controls. Results: Our analysis revealed that the PE group exhibited significantly elevated first-trimester serum levels of hepatocyte growth factor (HGF), interleukin (IL)-2Rα, IL-9, RANTES, tumor necrosis factor-β (TNF-β), total IgM, and total IgG, and aPS IgG optical density (OD) value, in addition to decreased first-trimester serum levels of PlGF and total IgA and aPS-IgG immune complexes (IC) OD value compared to the control group. The combination of the top five first-trimester serum biomarkers (total IgM, total IgG, PlGF, aPS IgG, and total IgA) achieved superior predictive value [area under the curve (AUC) and 95% confidence interval (CI): 0.983 (0.952-1.000)] for PE development compared to PlGF and PlGF/sFlt-1 independently [AUC and 95% CI: 0.825 (0.726-0.924) and 0.670 (0.539-0.800), respectively]. Conclusion: We identified novel first-trimester serum biomarkers and developed an effective prediction model integrating immune-related factors and PlGF for early PE detection, which could facilitate the development of early diagnostic strategies and provide immunological insight into the further mechanistic exploration of PE.

THU437 Oral Ulcers As A Clue To Bone Fragility

Abstract Disclosure: S. Sridhar: None. E.I. Krug: None. Introduction: Metabolic bone disease is common in celiac disease (CD) and can occur in patients without gastrointestinal symptoms. Successful treatment of malabsorption is associated with amelioration of bone loss. Recurrent aphthous stomatitis (RAS) may be the sole manifestation of CD (1). According to American College of Gastroenterology Guidelines, tissue transglutaminase (tTG)-IgA antibody and total IgA level is the single preferred test for detection of CD in adults due to reported sensitivity of 90-98% and specificity of 95-97%. No additional testing is typically recommended for patients without IgA deficiency (2). Case: The patient is a 58 year old woman with past medical history of RAS treated with prednisone, 5 mg daily for 10 years, facial and ocular rosacea, menopause at age 49, asthma, chronic back and neck pain, history of spontaneous rib fracture and L4 compression fractures during chiropractic manipulation, who had progressive bone loss despite ongoing treatment with oral bisphosphonates, calcium and vitamin D supplementation for 4 years with good adherence, and was referred for endocrine evaluation. Laboratory studies revealed TSH 1.94 mIU/L (0.4-4.5), 25(OH)vit D 41 ng/mL (30-100 ng/mL), PTH 31 pg/mL (14-64), Ca 9. mg/dL (8.6-10.4), albumin 4.1 mg/dL (3.6-5.1), Mg 2.1 mg/dL (1.5-2.5), tTG-IgA 1 U/mL (&amp;lt;4), total IgA 190 mg/dL (47-310), Gliadin deamidated peptide IgA Ab 11 Units (&amp;lt;20), Gliadin deamidated peptide IgG Ab (DGP-IgG) 44 Units (&amp;lt;20). Duodenal biopsy revealed diffuse increase in intraepithelial lymphocytes, acute and chronic inflammation of lamina propria, focally marked villous blunting consistent with CD. The patient reported complete resolution of RAS and rosacea symptoms within one month of starting a strict gluten free diet. She also noted marked improvement in neck and back pain. After 6 months repeat DGP-IgG was 13 Units. Treatment with teriparatide of 12 months duration resulted in 12.1% and 5.4% gain in bone density of lumbar spine and total hip respectively. Conclusion: CD should be suspected in patients with osteoporosis and extraintestinal conditions including RAS and, possibly, rosacea. CD has been reported in 2.83% of 247 patients with RAS screened for (tTG)-IgA and anti-endomysial IgA Abs (2). Rosacea has also been linked to CD in one study (3). Our case suggests that patients presenting with RAS may need to be tested for DGP-IgG reported to have a sensitivity of 92% and specificity of 100%, regardless of total IgA level.

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.

Celiac Disease in Uzbek Children: Insights into Disease Prevalence and Clinical Characteristics in Symptomatic Pediatric Patients.

A few studies on pediatric Celiac Disease (CD) are available from Central Asia. Recent immunogenetic research has highlighted that the HLA-DQ2/8 genetic predisposition to CD as well as the dietary intake of gluten in this geographical area, are comparable to other regions of the world where CD prevalence is known to be 1% or higher. This is a prospective and cross-sectional study investigating the prevalence and clinical characteristics of CD in symptomatic children referred to the pediatric gastroenterology department of a tertiary hospital in Uzbekistan from 1 September 2021, until 31 July 2022. In addition to collecting the relevant information related to clinical manifestations and laboratory analyses from the clinical files, a specific survey was also administered to patients' guardians. Serological, histopathological, and immunogenetic parameters specific to CD, fecal zonulin, and pancreatic elastases were assessed in CD patients. The study population consisted of 206 children. Overall, almost all of them (n = 192; 93.2%) were referred because of gastrointestinal manifestations, which were associated with extra-gastrointestinal manifestations in most cases (n = 153; 74.3%); a minority (n = 14; 6.8%) was mainly referred due short stature and/or growth failure only. Among all of these study participants, CD was diagnosed in 11 children (5.3%). Notably, although diarrhea was similarly reported in CD and non-CD patients, watery diarrhea (type 7 according to the Bristol stool scale) was much more frequently and significantly observed in the former group. All of these CD patients showed anti-tTG IgA 10 times higher than the upper normal limit, except one child with lower serum levels of total IgA; however, all of them received a diagnostic confirmation by histopathological analysis due to the lack of EMA testing in the country. Notably, most CD children (82%) showed a Marsh III histological grading. Around half patients (54.5%) showed zonulin values above the reference range, whereas none showed insufficient levels of pancreatic elastase. However, no correlation or association between zonulin and clinical, laboratory, histopathological, and immunogenetic parameters was found. This study may further suggest a relevant prevalence of CD in Uzbek children, based on this partial picture emerging from symptomatic patients only. Additionally, we highlighted the prevalence of typical CD forms with watery diarrhea, which should strongly support a full diagnostic work-up for CD in the local clinical setting. The high levels of anti-tTG IgA and high Marsh grade might also lead us to speculate a significant diagnostic delay despite the classical clinical expression of CD.

Combined oral intake of short and long fructans alters the gut microbiota in food allergy model mice and contributes to food allergy prevention

BackgroundIt has become clear that the intestinal microbiota plays a role in food allergies. The objective of this study was to assess the food allergy-preventive effects of combined intake of a short fructan (1-kestose [Kes]) and a long fructan (inulin ([Inu]) in an ovalbumin (OVA)-induced food allergy mouse model.ResultsOral administration of fructans lowered the allergenic symptom score and alleviated the decreases in rectal temperature and total IgA levels and increases in OVA-specific IgE and IgA levels induced by high-dose OVA challenge, and in particular, combined intake of Kes and Inu significantly suppressed the changes in all these parameters. The expression of the pro-inflammatory cytokine IL-4, which was increased in the allergy model group, was significantly suppressed by fructan administration, and the expression of the anti-inflammatory cytokine IL-10 was significantly increased upon Kes administration. 16 S rRNA amplicon sequencing of the gut microbiota and beta diversity analysis revealed that fructan administration may induce gut microbiota resistance to food allergy sensitization, rather than returning the gut microbiota to a non-sensitized state. The relative abundances of the genera Parabacteroides B 862,066 and Alloprevotella, which were significantly reduced by food allergy sensitization, were restored by fructan administration. In Parabacteroides, the relative abundances of Parabacteroides distasonis, Parabacteroides goldsteinii, and their fructan-degrading glycoside hydrolase family 32 gene copy numbers were increased upon Kes or Inu administration. The concentrations of short-chain fatty acids (acetate and propionate) and lactate were increased by fructan administration, especially significantly in the Kes + Inu, Kes, and Inu-fed (Inu, Kes + Inu) groups.ConclusionCombined intake of Kes and Inu suppressed allergy scores more effectively than single intake, suggesting that Kes and Inu have different allergy-preventive mechanisms. This indicates that the combined intake of these short and long fructans may have an allergy-preventive benefit.

Total serum IgA levels and HLA-DQB1*02:01 allelic status.

Immunoglobulin A Deficiency (IgAD) is the most common primary immunodeficiency and issignificantly associated with Celiac Disease (CD), which recognizes a specific background ofhuman leukocyte antigens (HLA) predisposition (including HLA-DQB1*02:01 allele). A numberof studies investigated the role of HLA in IgAD etiopathogenesis: HLA-DQB1*02 alleles areincluded in the main haplotypes linked to this primary immunodeficiency. In this preliminarystudy, we investigated the potential impact of HLA-DQB1*02:01 allelic status on total serum IgAlevels: 108 serum samples from the bone marrow donors' registry wereanalyzed for total IgA concentration with respect to the HLA-DQB1*02:01 status. Although totalserum IgA levels between HLA-DQB1*02:01 carriers and HLA-DQB1*02:01 negative donorswere not different, we observed a statistically significant difference (p=0.0118) in total serum IgAlevels among donors with low IgA concentration (<80mg/dL) in the sub-analysis between HLA-DQB1*02:01 positive group (including both homozygous and heterozygous carriers) compared toHLA-DQB1*02:01 negative donors. Our results might suggest a role of HLA-DQB1*02:01 allelicvariant in the determination of total serum IgA levels, at least in patients affected with IgAdeficiency and/or otherwise predisposed to it; however, larger and more standardized studies areneeded to confirm this speculation.