Evaluation of Celiac Disease by Minimally Invasive Biomarkers in a Spanish Pediatric Population.

BACKGROUND: The diagnosis of celiac disease (CD) has been substantially improved with the availability of highly sensitive CD-specific IgA-TG2, Ig-GDP, and IgA-EMA. The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) published (2012) and updated (2020) diagnostic criteria for CD in order to simplify CD diagnosis and to avoid biopsies in selected patients. METHODS: A prospective study including 5641 pediatric patients (0-16 years old) from January 2012 to January 2019 was performed. CD diagnosis was made according to the ESPGHAN algorithm. The objective of this study was to evaluate the utility of biomarkers and the relationship between TGA-IgA and EMA titers. RESULTS: CD diagnoses were confirmed in 113 patients, 110 were IgA-TG2-positive and 3 (2.7%) had IgA deficiency. The diagnosis was made by serologic tests in 95 (84.1%) patients. Only 18 (15.9%) patients underwent intestinal biopsy. We obtained 100% concordance between IgA-EMA and positive results for IgA-TG2 ≥ 10 ULN with IgA-EMA antibody titer ≥ 1:80. CONCLUSIONS: This study provides evidence of a positive correlation between IgA-TG2 antibody serum levels and IgA-EMA. The diagnosis could be guaranteed with strict application of IgA-TG2 values ≥ 10 ULN (confirmed by subsequent testing) plus the serological response to the gluten-free diet (GFD).

Red Cell Distribution Width as a Predictive Factor of Celiac Disease in Middle and Late Adulthood and Its Potential Utility as Celiac Disease Screening Criterion.

Red cell distribution width (RDW) could be of interest by its potential use in the assessment of celiac disorder (CD). The main objective of this study was to evaluate the case positive rate of CD and the utility of red cell distribution width (RDW) in the CD diagnosis. This prospective study included 9.066 middle adult (≥45 years old) and elderly patients (≥60 years old) from 2012 to 2021. CD diagnosis was performed by CD antibody tests (serology and Human Leucocyte Antigen genotype (HLA)) and biopsy. Gastrointestinal and extra-intestinal manifestations as well as hematological and biochemical parameters were analyzed. CD diagnoses were confirmed in 101 patients (median (IQR) age = 62 (52.3−73); 68.32% women) by serologic tests (100%) and intestinal biopsy (88.12%), showing mainly marked or complete atrophy (76.24%, MARSH 3a−c). Anemia was the most commonly presenting extra-intestinal manifestation (28.57%). Among 8975 individuals without CD, 168 age and sex matched were included. By comparison of CD and no CD individuals, we observed that high >14.3% RDW was exhibited by 58.40% and 35.2% individuals with CD and without CD, respectively. Furthermore, high RDW is associated with CD and grade III atrophy. We suggest that RDW could be used as a CD screening criterion.

Relationship between deoxycytidine kinase (DCK) genotypic variants and fludarabine toxicity in patients with follicular lymphoma.

DCK catalyzes the intracellular phosphorylation of fludarabine. The promoter and coding region of the DCK gene were analyzed in 74 follicular lymphoma (FL) patients receiving a therapeutic regimen that included fludarabine. DCK mRNA expression was quantified in a cohort of healthy donors. Four previously described genotypic variants, -360C>G, -201C>T (rs2306744), C28624T (rs11544786) and c.91+37G>C (rs9997790), as well as the new variant, -12C>G, were identified. Variant C28624T showed a lower risk of lymphopenia (P=0.04), but a higher risk of neutropenia (P=0.04). Statistical significance was found in bivariate logistic regression between lymphopenia and infectious episodes in the induction period (odds ratio 3.85, P=0.04).

Influence of MBL-2 mutations in the infection risk of patients with follicular lymphoma treated with rituximab, fludarabine, and cyclophosphamide.

The employment of current treatments based on chemotherapy and immunotherapy leads to inmunosuppression. The presence of mutations or polymorphisms in genes related to immune system might involve an additional disadvantage. The aim of the present study was to analyze mannose-binding lectin (MBL-2 gene) mutations and their association with severe infections and event-free survival in patients diagnosed with follicular lymphoma, treated uniformly, in the clinical trial LNHF-03. The results of this trial showed impressive clinical efficacy but was complicated with 80 documented infectious episodes. Patients were classified into two genotypic groups, AA and AO/OO, based on their haplotypic inheritance. Neither the number of infectious episodes nor differences in event-free survival was found as a function of MBL-2 groups. Other factors, including the lymphoma malignancy and the immune alterations associated with the disease, should be considered responsible for this observation.

Asymptomatic hyperuricemia and serum uric acid concentration correlate with subclinical atherosclerosis in psoriatic arthritis patients without clinically evident cardiovascular disease.

OBJECTIVE: To establish whether serum uric acid concentration correlates with carotid intima-media wall thickness (IMT) in a cohort of psoriatic arthritis (PsA) patients without overt cardiovascular (CV) disease or classic CV risk factors who attended a community hospital. METHODS: A series of 52 PsA patients were assessed by carotid ultrasonography. Carotid IMT and carotid plaques were measured in the right common carotid artery. A correlation between serum uric acid concentration and carotid IMT was assessed and receiver operating characteristic curves to evaluate the ability of serum uric acid to predict carotid IMT > 0.90 mm and carotid plaques were performed. RESULTS: PsA patients with hyperuricemia (n = 6 [11.5%]) had greater carotid IMT (mean +/- standard deviation: 0.89 +/- 0.20 mm) than those without hyperuricemia (n = 46 [89%]; 0.67 +/- 0.16 mm) (P = 0.01). Patients with carotid IMT < 0.60 mm had lower mean serum uric acid levels (4.7 +/- 1.2 mg/dL) than those with greater carotid IMT (5.3 +/- 1.7 mg/dL for patients with carotid IMT 0.76-0.90 mm and 6.4 +/- 1.3 mg/dL for those with carotid IMT > 0.90 mm; P for trend = 0.02). A significant correlation between carotid IMT and serum uric acid concentration was observed (r = 0.337; P = 0.01). High serum uric acid levels were associated with an increased risk of having carotid IMT > 0.90 mm (Odds ratio = 2.66 [95% confidence interval: 1.08-6.53], P = 0.03, area under receiver operating characteristic curve: 0.80) or with the presence of carotid plaques (Odds ratio = 1.85 [95%; confidence interval: 1.01-3.38], P = 0.05, area under receiver operating characteristic curve: 0.72). CONCLUSIONS: In PsA patients without clinically evident CV disease there is a correlation between serum uric acid concentration and subclinical atherosclerosis.

Giant cell arteritis: laboratory tests at the time of diagnosis in a series of 240 patients.

The outcome of a patient with giant cell arteritis (GCA) is closely related to the development of severe ischemic manifestations. In the current study we analyzed the implications of routine laboratory tests obtained at the time of diagnosis in the clinical spectrum of a series of 240 consecutive patients with biopsy-proven GCA at the single hospital for a defined population. We also examined whether the laboratory markers of inflammation may be predictors of severe ischemic manifestations (visual ischemic events, cerebrovascular accidents, jaw claudication, or large-artery stenosis of the extremities of recent onset), and their potential correlation. Anemia (hemoglobin <12 g/dL) was observed in 131 (54.6%) and thrombocytosis in 117 (48.8%) patients. Sixty-eight (28.3%) patients had leukocytosis. The percentage of patients showing a significant increase of alkaline phosphatase and hypoalbuminemia was similar (25% and 27.8%, respectively). The mean values of erythrocyte sedimentation rate (ESR) and C-reactive protein were 93 +/- 23 mm/h and 94 +/- 63 mg/L, respectively. A strong correlation among most laboratory markers of inflammation was observed. Anemia was more commonly observed in patients without severe ischemic manifestations (61.5% versus 48.9% in those with severe ischemic manifestation; p = 0.05) and in patients with constitutional syndrome or fever (p < 0.001). Patients with ESR greater than 100 mm/h exhibited more commonly constitutional syndrome (p < 0.001) and had a statistically significant reduction in the incidence of visual ischemic events (p < 0.025). Only 7 (22.6%) of the 31 patients who suffered permanent visual loss had an ESR at the time of disease diagnosis greater than 100 mm/h. However, in a multivariate logistic regression analysis, only anemia was found to be a negative predictor for the development of severe ischemic manifestations of GCA (odds ratio, 0.53; 95% confidence intervals, 0.30-0.94; p = 0.03). In conclusion, our results suggest that some laboratory markers of inflammation, in particular the presence of anemia, may negatively predict the risk of severe ischemic complications in GCA patients.