Prenatal genetic testing in 19 fetuses with corpus callosum abnormality

BackgroundCorpus callosum abnormality (CCA) can lead to epilepsy, moderate severe neurologic or mental retardation. The prognosis of CCA is closely related to genetic etiology. However, copy number variations (CNVs) associated with fetal CCA are still limited and need to be further identified. Only a few scattered cases have been reported to diagnose CCA by whole exome sequencing (WES).MethodsKaryotyping analysis, copy number variation sequencing (CNV‐seq), chromosomal microarray analysis (CMA) and WES were parallelly performed for prenatal diagnosis of 19 CCA cases.ResultsThe total detection rate of karyotyping analysis, CMA (or CNV‐seq) and WES were 15.79% (3/19), 21.05% (4/19) and 40.00% (2/5), respectively. Two cases (case 11 and case 15) were diagnosed as aneuploidy (47, XY, + 13 and 47, XX, + 21) by karyotyping analysis and CNV‐seq. Karyotyping analysis revealed an unknown origin fragment (46,XY,add(13)(p11.2)) in case 3, which was further confirmed to originate from p13.3p11.2 of chromosome 17 by CNV‐seq. CMA revealed arr1q43q44 (238923617–246964774) × 1(8.04 Mb) in case 8 with a negative result of chromosome karyotype. WES revealed that 2 of 5 cases with negative results of karyotyping and CNV‐seq or CMA carried pathogenic genes ALDH7A1 and ARID1B.ConclusionParallel genetic tests showed that CNV‐seq and CMA are able to identify additional, clinically significant cytogenetic information of CCA compared to karyotyping; WES significantly improves the detection rate of genetic etiology of CCA. For the patients with a negative results of CNV‐seq or CMA, further WES test is recommended.     

Detection of partial and/or complete Y chromosome microdeletions of azoospermia factor a (AZFa) sub‐region in infertile Iraqi patients with azoospermia and severe oligozoospermia

BackgroundThis study aimed to analyze the incidence of azoospermia factor a (AZFa) microdeletions in the Y chromosome and their association with male infertility in a population with azoospermia and severe oligozoospermia from Iraq.MethodsA total of 75 infertile Iraqi males and 25 healthy controls were included in this study. The semen analysis was performed to determine the azoospermia, severe oligozoospermia, or normal cases. The AZFa microdeletions were investigated using the real‐time polymerase chain reaction (real‐time PCR). Then, AZFa sub‐region deletions were investigated by a conventional PCR.ResultsIn total, 40 men with azoospermia and 35 men with severe oligozoospermia were selected. Out of 75 infertile males, 46 (61.3%) individuals had AZFa microdeletions, of whom 32 (69.6%) had partial deletion, while 14 (30.4%) males had complete deletion using real‐time PCR. The frequency of microdeletions was significantly different between the infertile and control group (p‐value < 0.00001). The proportion of AZFa microdeletions appeared higher in azoospermia men (72.5%, n = 29/40) than severe oligozoospermia men (48.6%, n = 17/35), but based on the conventional PCR results, only one azoospermia patient (2.2%) was shown to have complete AZFa deletion, while the other 45 patients (97.8%) had partial AZFa deletions.ConclusionIn this study, the partial AZFa microdeletions were more numerous than complete AZFa deletion. According to our results, the AZFa microdeletions might be associated with male infertility and spermatogenic failure. It is recommended to investigate the AZFa sub‐region microdeletions in patients that shown AZFa microdeletions in primary screening.     

A novel SRY pathogenic variant from a 46,XY female harboring a nonsense point mutation (G to A) in position 293

46,XY female is a genetic disorder characterized by gonad gender not consistent with chromosomal sex. The SRY gene mutation is a common cause of 46,XY reversal type 1 (OMIM: 400044). Peripheral blood was collected from a 46,XY female patient and her father. Sex chromosomes were confirmed by karyotype analysis and fluorescence in situ hybridization (FISH) detection of the specific probe of sex chromosomes with cultured lymphocytes. After extracting blood genomic DNA, SRY characteristic fluorescence peak was detected by quantitative fluorescence PCR (QF‐PCR) method. Whole exome was sequenced with NGS, and SRY gene was sequenced by Sanger sequencing, respectively. The chromosomes X and Y of the patient were confirmed by karyotype of 46,XY, and FISH specific probe of chromosome X and Y. SRY specific fluorescence peak was observed by QF‐PCR. The whole‐exome sequencing results showed chrY: 2655352(GRCh37): c.293G>A hemizygote mutation, confirmed by Sanger sequencing. The de novo mutation resulted in the mRNA encoding the tryptophan codon of 98 (UGG) change into a termination codon (UAG) (P.Trp98ter), and the translation process was terminated prematurely. The discovery of this novel mutation in the SRY gene helps elucidate the molecular mechanism of 46,XY female sex reversal and enriches such patients’ genetic mutation spectrum.     

Detection of partial deletion and mosaicism using quantitative fluorescent polymerase chain reaction: Case reports and a review of the literature

BackgroundAneuploidy of chromosomes 13, 18, 21, X, and Y can be detected by the quantitative fluorescence polymerase chain reaction (QF‐PCR) performed with short tandem repeat (STR) markers. Although QF‐PCR is designed to detect whole chromosome trisomy, the partial deletion or mosaic of chromosomes may also be detected.MethodsPartial deletion or mosaic of chromosomes in three cases was detected by QF‐PCR. Karyotyping and chromosome microarray analysis(CMA) were performed. We further reviewed the clinical utility of QF‐PCR in detecting mosaicisms and deletions/duplications.ResultsQF‐PCR demonstrated structurally abnormal 21, X, and Y chromosomes in primary amniotic cells. QF‐PCR results in these three cases showed abnormal peak height/peak area, which could not be interpreted according to the kit instructions. QF‐PCR results suggested that there were partial deletions or mosaicism, which were confirmed by karyotyping and CMA.ConclusionIn addition to detecting trisomies of whole chromosomes, QF‐PCR can also detect deletion and mosaicism of chromosomes 13, 18, 21, X, and Y, which could suggest the presence of copy number variants (CNVs). Additional testing with genetic technologies, such as karyotyping or microarrays, is recommended when an uninformative pattern is suspected.     

Targeted resequencing showing novel common and rare genetic variants increases the risk of asthma in the Chinese Han population

BackgroundAlthough studies have identified hundreds of genetic variants associated with asthma risk, a large fraction of heritability remains unexplained, especially in Chinese individuals.MethodsTo identify genetic risk factors for asthma in a Han Chinese population, 211 asthma‐related genes were first selected based on database searches. The genes were then sequenced for subjects in a Discovery Cohort (284 asthma patients and 205 older healthy controls) using targeted next‐generation sequencing. Bioinformatics analysis and statistical association analyses were performed to reveal the associations between rare/common variants and asthma, respectively. The identified common risk variants underwent a validation analysis using a Replication Cohort (664 patients and 650 controls).ResultsFirst, we identified 18 potentially functional rare loss‐of‐function (LOF) variants in 21/284 (7.4%) of the asthma cases. Second, using burden tests, we found that the asthma group had nominally significant (p < 0.05) burdens of rare nonsynonymous variants in 10 genes. Third, 23 common single‐nucleotide polymorphisms were associated with the risk of asthma, 7/23 (30.4%) and 9/23 (39.1%) of which were modestly significant (p < 9.1 × 10⁻⁴) in the Replication Cohort and Combined Cohort, respectively. According to our cumulative risk model involving the modestly associated alleles, middle‐ and high‐risk subjects had a 2.0‐fold (95% CI: 1.621–2.423, p = 2.624 × 10⁻¹¹) and 6.0‐fold (95% CI: 3.623–10.156, p = 7.086 × 10⁻¹²) increased risk of asthma, respectively, compared with low‐risk subjects.ConclusionThis study revealed novel rare and common genetic risk factors for asthma, and provided a cumulative risk model for asthma risk prediction and stratification in Han Chinese individuals.     

Identification of a compound heterozygous missense mutation in LAMA2 gene from a patient with merosin‐deficient congenital muscular dystrophy type 1A

BackgroundMerosin‐deficient congenital muscular dystrophy type 1A (MDC1A) is occurred by mutations in LAMA2 gene that encodes the laminin α2 chain (merosin). MDC1A is a predominant subtype of congenital muscular dystrophy. Herein, we identified two missense mutations in LAMA2 gene in compound heterozygous status in an Iranian patient with MDC1A using whole‐exome sequencing (WES).MethodsIn the present study, we evaluated genetic alterations in an Iranian 35‐month‐old boy with MDC1A and his healthy family using WES method. The identified mutations further confirmed by Sanger sequencing method. Finally, in silico analysis was conducted to further evaluation of molecular function of the identified genetic variants.ResultsWe identified two potentially pathogenic missense mutations in compound heterozygous state (c.7681G>A p.Gly2561Ser and c.4840A>G p.Asn1614Asp) in LAMA2 gene as contributing to the MDC1A phenotype. The healthy parents of our proband are single heterozygous for identified mutations. These variants were found to be pathogenic by in silico analysis.ConclusionsIn general, we successfully identified LAMA2 gene mutations in an Iranian patient with MDC1A using WES. The identified mutations in LAMA2 gene can be useful in genetic counseling, prenatal diagnosis, and predicting prognosis of MDC1A.     

Longitudinal variation of circulating Inc‐ITSN1‐2: A novel biomarker reflecting disease severity,inflammation, recurrence,and death risk in acute ischemic stroke patients

BackgroundLong noncoding RNA intersectin 1–2 (lnc‐ITSN1‐2) regulates inflammation and neuronal apoptosis; meanwhile, the latter two factors participate in the pathogenesis of acute ischemic stroke (AIS). Therefore, this study detected lnc‐ITSN1‐2 at multiple time points, aiming to explore its longitudinal variation and clinical value in the management of AIS patients.MethodsThe current study enrolled 102 AIS patients, then detected their lnc‐ITSN1‐2 in peripheral blood mononuclear cell (PBMC) at baseline (D0), day (D)1, D3, D7, month (M)1, M3, M6, and year (Y)1 after admission using RT‐qPCR. Additionally, lnc‐ITSN1‐2 in PBMC of 50 controls was also detected.ResultsLnc‐ITSN1‐2 was up‐regulated in AIS patients than that in controls (p < 0.001). Lnc‐ITSN1‐2 positively associated with NIHSS score, TNF‐α, and IL‐17A (all p < 0.050) but was not linked with IL‐6 (p = 0.093) in AIS patients. Notably, lnc‐ITSN1‐2 was gradually increased from D0 to D3; while it switched to decrease from D3 to Y1 in AIS patients. Lnc‐ITSN1‐2 disclosed similar longitudinal variation during 1 year in non‐recurrent (p < 0.001), recurrent (p = 0.001), and survived patients (p < 0.001), while the variation of lnc‐ITSN1‐2 in died patients was not obvious (p = 0.132). More importantly, lnc‐ITSN1‐2 at D0, D3, D7, M1, M3, M6, and Y1 was higher in recurrent AIS patients than that in non‐recurrent AIS patients (all p < 0.050); moreover, lnc‐ITSN1‐2 at D3, D7, M1, M3, and M6 was up‐regulated in died AIS patients than AIS survivors (all p < 0.050).ConclusionThe dynamic variation of Inc‐ITSN1‐2 could serve as a biomarker reflecting disease severity, inflammatory cytokines, recurrence, and death risk in AIS patients.     

The influence of SARS‐CoV‐2 on semen parameters of infected infertile male in comparison with those that noninfected

BackgroundCoronavirus disease (COVID‐19) is an infectious disease caused by SARS COV‐2 that has spread globally, the virus can cause different pathological alterations in many organs, such as the lung, kidney, and testis. The study aimed to determine the effect of COVID‐19 on the seminal fluid parameters of infected infertile males compared with those who are noninfected.MethodsThe study was performed in Al‐Hussein Teaching Hospital during the period from September to November, 2021 and it involved 318 patients. The patients’ info included age, address, and vaccination. The sperm count, activity, and morphology were detected using Computer‐assisted semen analysis CASA (Microptic‐Spain) according to the WHO manual.ResultsThere were high significant differences between the infertile males who were infected with COVID‐ 19 and those who were vaccinated (X ² = 12.509, p = 0.001). A high significant relation (p < 0.001) was recorded between types of infection severity and volume of semen (p < 0.001) and nonprogress life sperm (C) (p < 0.001). While significant differences were shown in the moderate progression sperm (B) (p = 0.012), and morphology (p = 0.02), respectively. High significant differences were reported between the types of infection severity (count of the sperm, presence of pus, B, C and D), (p < 0.001), while a significant difference was shown between severity types in relation to A and morphology of the sperms (p = 0.021 and 0.015), respectively.ConclusionThe severity of COVID‐19 has a significant impact on infertility and sperm parameters, particularly progression and sperm morphology, despite the fact that these parameters are unrelated to vaccination.     

Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 in rheumatoid arthritis: Longitudinal change after treatment and correlation with treatment efficacy of tumor necrosis factor inhibitors

BackgroundMucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT1) correlates with treatment outcomes in inflammatory bowel disease and rheumatoid arthritis (RA). This study aimed to further evaluate the MALT1 longitudinal change and its relationship with tumor necrosis factor inhibitors (TNFi) response in RA patients.MethodsSeventy‐one RA patients receiving TNFi [etanercept (n = 42) or adalimumab (n = 29)] were enrolled. MALT1 was detected by RT‐qPCR in peripheral blood samples of RA patients before treatment (W0), at week (W)4, W12, and W24 after treatment. RA patients were divided into response/non‐response, remission/non‐remission patients according to their treatment outcome at W24. Meanwhile, MALT1 was also detected by RT‐qPCR in 30 osteoarthritis patients and 30 healthy controls (HCs).ResultsMucosa‐associated lymphoid tissue lymphoma translocation protein 1 was elevated in RA patients compared with HCs (Z=−6.392, p < 0.001) and osteoarthritis patients (Z = −5.020, p < 0.001). In RA patients, MALT1 was positively correlated with C‐reactive protein (r_s  = 0.347, p = 0.003), but not other clinical characteristics, treatment history, or current TNFi category. Meanwhile, MALT1 decreased from W0 to W12 in total RA patients (x²  = 86.455, p < 0.001), etanercept subgroup (x²  = 46.636, p < 0.001), and adalimumab subgroup (x²  = 41.291, p < 0.001). Moreover, MALT1 at W24 (p = 0.012) was decreased in response patients compared with non‐response patients; MALT1 at W12 (p = 0.027) and W24 (p = 0.010) were reduced in remission patients than non‐remission patients. In etanercept subgroup, MALT1 at W24 (p = 0.013) was decreased in response patients compared with non‐response patients. In adalimumab subgroup, MALT1 at W24 (p = 0.015) was lower in remission patients than non‐remission patients.ConclusionMucosa‐associated lymphoid tissue lymphoma translocation protein 1 reduction after treatment is associated with response and remission to TNFi in RA patients.     

Early platelet elevation after complete remission as a prognostic marker of favourable outcomes in favourable‐ and intermediate‐risk acute myeloid leukaemia: A retrospective study

ObjectivesPlatelet (PLT) recovery after chemotherapy is associated with the prognosis of patients with acute myeloid leukaemia (AML). This study aimed to explore the prognostic significance of early high PLT values in patients with de novo non‐M3 AML who achieved first complete remission (CR).MethodsA total of 206 patients with de novo non‐M3 AML were analysed in this retrospective study. A receiver operating characteristic (ROC) curve was used to determine the optimal PLT cut‐off. The overall survival (OS) and relapse‐free survival (RFS) were assessed using Kaplan‐Meier and Cox regression analyses.Results312×10⁹/L was confined as the cut‐off of the PLT count. The estimated 3‐year OS of patients with high PLT was higher than that of their counterparts (72.3% vs. 34.6%, p = 0.001). In subgroup analysis, patients with high PLT had better OS in the favourable‐ and intermediate‐risk (non‐adverse‐risk) AML (p = 0.001). The estimated 3‐year RFS for the high and low PLT groups was 75.1% and 45.7% respectively (p = 0.078). Multivariate analyses revealed that high PLT count was an independent favourable variable for OS (HR = 0.264, p < 0.001) and RFS (HR = 0.375, p = 0.011) in the non‐adverse‐risk group.ConclusionOur results showed that early high PLT count recovery at first CR in non‐adverse‐risk AML patients is a positive prognostic marker for survival outcomes.     

The effect of A1298c polymorphism of the MTHFR gene on anti‐Müllerian hormone levels: experimental and Web‐based analysis

BackgroundThe 5,10‐methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionine metabolism, which is expressed in human oocytes and preimplantation. Due to the involvement of MTHFR in female reproduction, we tend to evaluate the influence of MTHFR A1298C polymorphism on ovarian marker reserves such as serum anti‐Müllerian hormone (AMH) levels in women after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).MethodsA total of 100 women, who underwent ART treatment due to male factor infertility, were recruited into this study. MTHFR A1298C polymorphism was detected by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) technique, and serum AMH concentrations were measured by an ultrasensitive enzyme‐linked immunosorbent assay (ELISA).ResultsWomen with the CC genotype had higher AMH levels (4.15 ± 1.67 ng/ml), albeit not significant, than carriers with other genotypes after ovarian stimulation. No significant differences existed in terms of miscarriage and live birth rates among different genotype groups.ConclusionThe presence of the C mutant allele of the 1298 polymorphism in the MTHFR gene led to an increasing trend in serum AMH concentrations; however, the numbers of oocytes retrieved decreased in women with mutated genotypes. The influence of the MTHFR C677T polymorphism on embryo quality and pregnancy rate after ART cycles remains unclear.     

Identification and validation of PGLS as a metabolic target for early screening and prognostic monitoring of gastric cancer

BackgroundGastric cancer is the third leading cause of cancer‐related death in the world. The purpose of the present study is to investigate the expression and prognostic significance of 6‐phosphogluconolactonase (PGLS) in gastric cancer.MethodsThe protein extracted from a panel of four pairs of gastric cancer tissues and adjacent tissues, labeled with iTRAQ (8‐plex) reagents, and followed by LC‐ESI‐MS/MS. The expressions of proteins were further validated by immunohistochemistry analysis. The expression levels of mRNA were analyzed and validated in the Oncomine database. The correlations of PGLS with prognostic outcomes were evaluated with Kaplan‐Meier plotter database.ResultsThe present study found that PGLS was significantly up‐regulated in gastric cancer by using iTRAQ‐based proteomics and immunohistochemistry analysis. The sensitivity of PGLS in gastric cancer was 72.9%. The high expression of PGLS was significantly correlated with TNM staging in gastric cancer (p = 0.02). The overexpression of PGLS predicts worse overall survival (OS) and post‐progression survival (PPS) for gastric cancer (OS, HR = 1.48, p = 2.1e‐05; PPS, HR = 1.35, p = 0.015). Specifically, the high PGLS expression predicts poor OS, PPS in male gastric cancer patients, in patients with lymph node metastasis and in patients with Her‐2 (‐).ConclusionsThese findings suggested that PGLS was aberrantly expressed in gastric cancer and predicts poor overall survival, post‐progression survival for gastric cancer patients. The present study collectively supported that PGLS is an important target for early determining and follow‐up monitoring for gastric cancer.     

Real‐life effectiveness of biological therapies on symptoms in severe asthma with comorbid CRSwNP

BackgroundWe aimed to evaluate the effectiveness of different antibody therapies on nasal polyp symptoms in patients treated for severe asthma.MethodsWe performed a retrospective analysis of patients with severe asthma and comorbid CRSwNP who were treated with anti‐IgE, anti‐IL‐5/R or anti‐IL‐4R. CRSwNP symptom burden was evaluated before and after 6 months of therapy.ResultsFifty patients were included hereof treated with anti‐IgE: 9, anti‐IL‐5/R: 26 and anti‐IL‐4R: 15 patients. At baseline median SNOT‐20 was similar among groups (anti‐IgE: 55, anti‐IL‐5/R: 52 and anti‐IL‐4R: 56, p = 0.76), median visual analogue scale (VAS) for nasal symptoms was 4, 7 and 8 (p = 0.14) and VAS for total symptoms was higher in the anti‐IL‐4R group (4, 5 and 8, p = 0.002). After 6 months SNOT‐20 improved significantly in all patient groups with median improvement of anti‐IgE: −8 (p < 0.01), anti‐IL‐5/R: −13 (p < 0.001) and anti‐IL‐4R: −18 (p < 0.001), with larger improvement in the anti‐IL‐4R group than in anti‐IgE (p < 0.001) and anti‐IL‐5/R (p < 0.001) groups. VAS nasal symptoms improved by median anti‐IgE: 0 (n.s.), anti‐IL‐5/R: −1 (p < 0.01) and anti‐IL‐4R: −3 (p < 0.001), VAS total symptoms by anti‐IgE: −1 (n.s.), anti‐IL‐5/R: −2 (p < 0.001) and anti‐IL‐4R: −2 (p < 0.001).ConclusionsTreatment by all antibodies showed effectiveness in reducing symptoms of CRSwNP in patients with severe asthma, with the largest reduction observed in anti‐IL‐4R‐treated patients.     

Comparison of IL‐6 measurement methods with a special emphasis on COVID‐19 patients according to equipment and sample type

BackgroundInterleukin‐6 (IL‐6) is a multifunctional cytokine associated with various diseases, including coronavirus disease (COVID‐19). Although IL‐6 levels can be assessed using serum samples, use of the AFIAS (Boditech Med Inc.) automated immunoassay analyzer enables quick and simple measurement of IL‐6 levels in both serum and whole blood specimens. This study aimed to assess the correlation between IL‐6 measurements obtained from the AFIAS IL‐6 assay and Elecsys IL‐6 assay (Roche Diagnostics). Additionally, utilization of the AFIAS IL‐6 assay was evaluated.MethodsThe IL‐6 levels from 113 serum samples quantified using two assay systems were evaluated for their degree of correlation. Meanwhile, the linearity, analytical sensitivity, and precision/reproducibility of the AFIAS IL‐6 assay were also assessed.ResultsQuantification of IL‐6 with the AFIAS IL‐6 and Elecsys IL‐6 assays showed excellent agreement (kappa 0.802) and were found to be correlated (y = −0.2781 + 1.068x; 95% confidence interval: 1.007–1.124). AFIAS IL‐6 showed good analytical performances. IL‐6 levels were significantly higher in deceased patients compared to those with non‐complicated disease and those who were intubated (p = 0.002 and p < 0.0001, respectively). Finally, IL‐6 levels more accurately predicted poor prognosis in patients, than did C‐reactive protein (area under the curve, 0.716 vs. 0.634).ConclusionThe overall analytical performance of the AFIAS assay was comparable to that of the Elecsys IL‐6 assay. In light of the ongoing COVID‐19 pandemic, the AFIAS may be an attractive tool for measuring IL‐6 levels.     

Clinical value of serum miR‐320‐3p expression in predicting the prognosis of sepsis‐induced acute kidney injury

BackgroundFor investigating the expression of miR‐320‐3p in children with sepsis‐induced acute kidney injury (AKI) and its prognostic value.MethodsA total of 142 patients were grouped into a survival group (n = 95) and death group (n = 47), which was based on their 28‐day survival. Serum degrees of miR‐320‐3p, neutrophil gelatinase‐associated lipid carrier protein (NGAL) and kidney injury molecule‐1 (KIM‐1) were detected. The Acute Physiology and Chronic Health scoring system Ⅱ (APACHE Ⅱ) marks were recorded. Target gene forecast and functional enrichment discussion of miR‐320‐3p were performed, and a protein–protein interaction (PPI) network diagram was plotted by applying bioinformatics methods. Multivariate logistic regression, ROC curve and Pearson correlation analysis were applied.ResultsThe death group showed greatly higher serum levels of miR‐320‐3p, KIM‐1 and APACHE Ⅱ scores than the survival group (p < 0.01). Multivariate logistic regression analysis showed that levels of miR‐320‐3p, NGAL, KIM‐1 and APACHE Ⅱ scores were independent risk elements for death in sepsis children with AKI (p < 0.01). According to ROC curve analysis, the region under the curve (0.963, 95% CI: 0.908–0.996) of miR‐320‐3p, NGAL, KIM‐1 levels and APACHE Ⅱ scores combined to forecast the death of kids suffering from sepsis and AKI were the biggest. According to correlation analysis, the expression degree of serum miR‐320‐3p in the death group was positively correlated with NGAL, KIM‐1 and APACHE Ⅱ scores (all p < 0.01).ConclusionsThe expression level of serum miR‐320‐3p in children with sepsis‐induced AKI was significantly increased, and the combination of NGAL, KIM‐1 and APACHE Ⅱ scores has good value for prognosis prediction in children.     

Frequency of serological markers of rheumatoid arthritis in adult patients with active celiac disease

BackgroundCeliac disease (CD) and rheumatoid arthritis (RA) are multisystem autoimmune diseases affecting 1% of general populationa. Both diseases share genetic and immunological features.AimIn this retrospective study, we aim to determine the frequency of auto‐antibodies of RA in adult patients with CD.Materials and methodsSeventy seven adult patients with active CD were included in the present study. Ninety healthy blood donors (HBD) served as control group. Anti‐cyclic citrullinated peptides antibodies (CCP‐Ab) and rheumatoid factors (RF; IgA, IgG and IgM) were determined by enzyme linked immunosorbent assay (ELISA) for patients and control group. For statistical analysis, we used Chi‐square or Fisher''s exact test.ResultsOur study included 77 adult patients with active celiac disease (57 female, 20 male). Twenty‐four (31.2%) active celiac patients and 7 (7.8%) blood donors had CCP‐Ab or RF (31.2% vs 7.8%, p < 10–4). Only two patients (2.6%) had both CCP‐Ab and RF. IgA was the predominant isotype of RF in celiac patients (n = 18; 23.4%) while none of healthy blood donors had RF‐IgA (23.4% vs 0.0%, p < 10–4).ConclusionThe current study has shown that CD is associated with a high frequency of RF‐IgA suggesting that celiac patients could be at a higher risk of developing RA.     

Association of end‐stage renal disease with HLA phenotypes and panel reactive antibodies in patients awaiting renal transplantation in Hunan Province

ObjectivesTo explore the immune‐related genetic susceptibility of human leukocyte antigen (HLA) alleles and their correlation with panel reactive antibody (PRA) generation during end‐stage renal disease (ESRD) progression.Materials and methodsData of the expression patterns of HLA‐A, ‐B, and ‐DR alleles and PRAs of 347 ESRD patients awaiting renal transplantation in Hunan Province from 2015 to 2019 were retrospectively studied. The polymerase chain reaction with sequence‐specific primers was used for HLA genotyping and the enzyme‐linked immunosorbent assay for PRA detection. SPSS 21.0 software was used for all allele frequency and statistical analyses.ResultsThirteen HLA‐A, 25 HLA‐B, and 13 HLA‐DR alleles were expressed. The allele frequencies of HLA‐A2, ‐B48, ‐B52, and ‐B55 were significantly higher in the case group than in the control group (p < 0.05), whereas that of HLA‐B60 was significantly higher in the control group (p < 0.05). The frequency of HLA alleles in the PRA‐positive group was significantly higher in females than in males (p < 0.05). The allele frequencies of HLA‐A2, ‐B38, and ‐B46 were significantly higher in the PRA‐positive group than in the PRA‐negative one (p < 0.05), whereas that of HLA‐60 was significantly higher in the PRA‐negative group (p < 0.05).ConclusionHLA‐A2, ‐B48, ‐B52, and ‐B55 may be the ESRD susceptibility alleles in Han Chinese patients in Hunan Province, whereas HLA‐B60 may be the protective allele. Patients carrying HLA‐A2, ‐B38, and ‐B46 are more likely to develop PRA positivity, whereas the opposite is true for those with HLA‐B60.