Serum Immunoglobulin A Levels Research Articles

Relationship between Serum IgA concentration and epileptic seizures in children: A prospective study

Purpose. This study investigated the relationship between serum immunoglobulin A (IgA) concentration and epileptic seizures in children. Methods. Pediatric patients with epilepsy were included in this cross-sectional investigation. Serum IgA levels were analyzed using a biochemical analyzer during admission for initial diagnosis before any medical treatment was administered. Results. Among the 94 patients, 19.1% had decreased serum IgA levels, with a median value of 0.57 g/L. No significant relationship existed between serum IgA concentration and gender, age, epilepsy type, seizure duration or epilepsy waves. Children with low IgA levels experienced more spastic episodes and had a higher seizure frequency compared to those without decreased IgA levels. Changes in serum IgA levels were significantly associated with seizure frequency after three months of treatment. Initially, the occurrence of seizures in the low IgA group was 10.5 times lower than in the non-low IgA group, but, after three months, the low IgA group had a significantly higher seizure rate (72.2%) compared to the non-low IgA group (19.7%). After six months, the low IgA group had a higher proportion of children without seizures (100% versus 84.8%), although the difference was not statistically significant. Conclusion. Serum IgA concentration plays a crucial role in diagnosing and predicting outcomes for pediatric epilepsy.

Abstract 1408: Intrahepatic IgA complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of HCC

Abstract Background and Aims: Cancer-associated fibroblasts (CAFs) are activated fibroblasts that play key roles in the tumor microenvironment (TME). Immunoglobulin A (IgA) contributes to inflammation and anti-tumor immunity dismantling in the human liver. We investigated the effects of the IgA complex on CAFs in the TME of hepatocellular carcinoma (HCC). Approach and Results: CAF dynamics in HCC TME were analyzed via single-cell RNA sequencing of HCC samples. CAFs were isolated from 40 HCC samples. The isolated CAFs were treated with mock or serum-derived IgA dimers. Following treatment with the mock or serum IgA dimers in vitro, co-culture experiments were performed using CAF and CD8+ T cells. Single-cell analysis showed that sub-cluster proportions in the CAF-fibroblast activation protein-α (FAP) matrix were significantly increased in patients with high serum IgA levels. We were performed flow cytometry on fresh surgical tissues and observed a significant increase in the mean fluorescence intensity (MFI) of FAP in the CD68+ cells from patients with high serum IgA levels compared to those with low serum IgA levels (p<0.001). We validated that the transferrin receptor (CD71) is expressed in CAFs (p<0.01). IgA-treated CAFs exhibited higher programmed death-ligand 1 (PD-L1) expression levels than mock-treated CAFs (p<0.05). Co-culture with CAFs induced the attenuation of the cytotoxic function of activated CD8+ T cell, and these cells co-cultured with IgA-treated CAFs exhibited increased expression levels of programmed death-1 (PD-1) compared to those co-cultured with mock-treated CAFs (p<0.05). Conclusions: Intrahepatic IgA induces polarization of HCC CAFs into more malignant matrix phenotype and attenuates cytotoxic T cell function. Our study uncovers five dynamic CAF subpopulations within HCC tissues and highlights their potential roles in tumor progression and immune suppression. Citation Format: Pil Soo Sung. Intrahepatic IgA complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of HCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1408.

Relationship between serum IgA levels and low percentage forced expiratory volume in the first second in asthma

Immunoglobulin A (IgA) is suggested to have pathogenic effects in respiratory inflammatory diseases, including asthma. We aimed to analyze the relationship between serum IgA, and clinical indicators and biomarkers of asthma. The present study was a post hoc analysis of the NHOM Asthma Study. In the present study, serum IgA was measured using serum samples stored. We determined an association between the serum IgA level and clinical variables and biomarkers using multivariate linear regression and analyzed the differences in clinical indices between IgA high- and IgA low-asthma. In the present study, 572 patients with asthma were included in the final analysis. Lower percentage forced expiratory volume in the first second (%FEV1), higher serum eotaxin levels, lower serum ST2 levels, and higher serum MIP-1β levels, were independently and significantly associated with higher serum IgA levels among asthma patients by multivariate linear regression analysis (%FEV1, 95% confidence interval [CI], -8.18– -0.613, p < 0.05; eotaxin, 95% CI, 8.95–46.69, p < 0.001; ST2, 95% CI, -73.71– -7.37, p < 0.05; and MIP-1β, 95% CI, 1.47–18.71, p < 0.05). Furthermore, IgA high-asthma (serum IgA ≥ 238 mg/dL, n = 270) and IgA low-asthma (serum IgA < 238 mg/dL, n = 302) were compared separately. %FEV1 was significantly lower, the percentage of atopy was higher, and serum MIP-1β level was higher in IgA high-asthma. The present study suggests that serum IgA may be involved in the worsening of asthma outcomes, as assessed by %FEV1 and enhanced inflammation via elevated serum MIP-1β.

Evaluation of the clinical use and impact of Miao medicine's anti influenza mask on IgA in human serum and SIgA in nasal mucosa

Purpose: To investigate the clinical use of anti-influenza mask of Miao medicine, and its effect on human serum immunoglobulin A (IgA) as well as nasal mucosa secretory immunoglobulin A (SIgA).&#x0D; Methods: 500 patients without COVID-19 in QianDongNanZhou Hospital of Traditional Chinese Medicine from January 2020 to September 2022 were selected and randomly divided into study and control groups, with 250 patients in each group. Both groups wore masks for three months. Control group was given disposable medical surgical three-layer melt-blown non-woven masks, while study group was given Miao medicine anti-infection masks. Serum IgA and SIgA levels were compared before and after wearing masks in both groups.&#x0D; Results: Prior to intervention, serum IgA and SIgA levels in nasal mucosa were not significantly different (p &gt; 0.05). There were also no significant differences in blood IgA levels between control and study groups. Before wearing masks, the study group had higher levels of blood IgA and nasal mucosal SIgA than control group. After wearing masks, nasal mucosa SIgA antibody levels and blood IgA antibody levels were significantly higher in the study group compared to control group (p &lt; 0.001). The frequency of adverse responses did not significantly differ between the two groups (p &gt; 0.05).&#x0D; Conclusion: Miao medicine anti-infection masks are safe and raise serum levels of COVID-19 IgA antibodies and nasal mucosa SIgA levels in populations susceptible to COVID-19. These properties need to be compared among different races for the purpose of validation

Influenza vaccination as a prognostic factor of humoral IgA responses to SARS-CoV-2 infection.

There is evidence that influenza vaccination may provide additional benefits by inducing training of innate immunity and increasing humoral responses to heterologous challenges. Immunoglobulin A (IgA) antibodies dominate the early phase of the adaptive response to SARS-CoV-2 infection, but whether their production may be associated with previous influenza vaccination has not been a subject of any study. This study compared serum SARS-CoV-2-specific IgA responses, measured with Microblot-Array assay, in individuals who experienced COVID-19 (N = 1318) and differed in the status of the seasonal influenza vaccine, age, sex, and disease severity. Influenza-vaccinated individuals had a higher seroprevalence of IgA antibodies against nucleocapsid (anti-NP; by 10.1%), receptor-binding domain of spike protein (anti-RBD; by 11.8%) and the S2 subunit of spike protein (anti-S2; by 6.8%). Multivariate analysis, including age, sex, and COVID-19 severity, confirmed that receiving the influenza vaccine was associated with higher odds of being seropositive for anti-NP (OR, 95% CI = 1.57, 1.2-2.0), anti-RBD (OR, 95% CI = 1.6, 1.3-2.0), and anti-S2 (OR, 95% CI = 1.9, 1.4-2.7), as well as being seropositive for at least one anti-SARS-CoV-2 IgA antibody (OR, 95% CI = 1.7, 1.3-2.1) and all three of them (OR, 95% CI = 2.6, 1.7-4.0). Age ≥ 50 years was an additional factor predicting better IgA responses. However, the concentration of particular antibodies in seropositive subjects did not differ in relation to the influenza vaccination status. The study evidenced that influenza vaccination was associated with improved serum IgA levels produced in response to SARS-CoV-2 infection. Further studies are necessary to assess whether trained immunity is involved in the observed phenomenon.

Effects of dietary tryptophan supplementation on rectal temperature, humoral immunity, and cecal microflora composition of heat-stressed broilers.

This trial aimed to determine the effects of tryptophan (Trp) on the rectal temperature, hormone, humoral immunity, and cecal microflora composition in broiler chickens under heat stress (HS). One hundred and eighty 18 days-old female Arbor Acres broilers were randomly divided into three treatment groups, with six replicates of ten birds in each replicate. The broilers were either raised under thermoneutral conditions (TN, 23 ± 1°C) or subjected to heat stress (34 ± 1°C for 8 h daily). The TN group received a basal diet, and another two heat-stressed groups were fed the basal diet (HS) or the basal diet supplemented with 0.18% Trp (HS + 0.18% Trp) for 21 consecutive days. The basal diet contained 0.18% Trp. Results revealed that HS increased the rectal temperature, serum epinephrine (EPI), and corticotropin-releasing hormone (CRH) concentrations (p < 0.05), reduced the bursal index, the levels of serum immunoglobulin A (IgA), IgG, IgM, and serotonin (5-HT) as well as the relative abundance of Actinobacteria in cecum (p < 0.05) compared with the TN group. Dietary supplementation of Trp decreased the rectal temperature, serum dopamine (DA), EPI, and the levels of CRH and L-kynurenine (p < 0.05), increased the bursal index, the levels of serum IgA, IgM, and 5-HT as well as the relative abundance of Ruminococcus torques group in cecum of heat-stressed broilers (p < 0.05) compared to HS group. In conclusion, dietary Trp supplementation decreased rectal temperature, improved cecal microbiota community and Trp metabolism, and enhanced humoral immunity of heat-stressed broilers.

Immune function, gastrointestinal hormone levels, and their clinical significance in patients with gastric ulcers complicated with depression.

Gastric ulcer (GU) is a common digestive tract disease, and medical records of GU combined with depression are increasingly common. Currently, the risk factors and pathogenesis of GU complicated with depression remain unclear. Low immune function and gastrointestinal hormone levels may also be significant risk factors. Therefore, this study explored the immune function and gastrointestinal hormone levels in patients with GU combined with depression. To explore the immune function, gastrointestinal hormone level, and clinical significance of patients with GU combined with depression. A retrospective analysis was conducted on 300 patients with GU combined with depression admitted to Guizhou Provincial People's Hospital from January 2021 to June 2022 as the study subjects. According to the Hamilton Depression Scale (HAMD) score, patients were divided into mild-to-moderate (n = 210) and heavy (n = 90) groups. Basic data, immune function indices [immunoglobulin A (IgA), IgM, IgG, serum CD4+ and CD8+ percentage, and CD4+/CD8+ ratio], and gastrointestinal hormone indices [serum gastrin (GAS), cholecystokinin (CCK), and motilin (MTL) levels] were collected. The basic data of the two groups were compared, and the immune function and gastrointestinal hormone indices were analyzed. Multivariate logistic regression was used to analyze the factors influencing the severity of GU complicated with depression. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to analyze the value of the immune function index, gastrointestinal hormone index, and combined index in predicting the severity of GU complicated with depression. There were no marked differences in sex, age, body mass index, abdominal distension, abdominal pain, belching, nausea, vomiting, or sleep disorders between the heavy and mild-to-moderate groups (P > 0.05). There was a marked difference in the family history of depression between the heavy and mild-to-moderate groups (P < 0.05). There were significant differences in serum IgA and IgM levels and serum CD4+, CD8+, and CD4+/CD8+ ratios between the heavy and mild-to-moderate groups (P < 0.05). Multivariate analysis showed that IgA, IgM, GAS, and CCK serum levels influenced the severity of GU with depression (P < 0.05). The AUC of the ROC curve for serum IgA level predicting GU with depression severity was 0.808 [95% confidence interval (CI): 0.760-0.857], the AUC of the serum IgM level was 0.757 (95%CI: 0.700-0.814), the AUC of the serum GAS level was 0.853 (95%CI: 0.810-0.897), the AUC of the serum CCK level was 0.762 (95%CI: 0.709-0.822), the AUC of immune function (IgA, IgM) and gastrointestinal hormone levels (GAS, CCK) for the prediction of GU with depression severity was 0.958 (95%CI: 0.933-0.976). Important factors influencing GU complicated with depression are serum IgA, IgM, GAS, and CCK indicators. They can be used as indicators to predict the severity of GU complicated with depression.

Immunoglobulin A and complement C4 are involved in the progression of liver fibrosis in patients with chronic hepatitis B.

To explore the relationship between immunoglobulin A (IgA), complement C4, and liver fibrosis (L.F.) progression (LFP) in patients with chronic hepatitis B (CHB). This is a retrospective cohort study of CHB patients who received liver biopsies. Relevant data, including demographics, clinical serum markers, and immunological results obtained during liver biopsies, were collected and analyzed to assess and verify the relationship between IgA, C4, and LFP. This study included 1,938 CHB patients, of whom 132 received two liver biopsies (group 1). Thirty (22.7%) of these patients were diagnosed with LFP (increase in L.F. stage (Scheuer score F≥1)). IgA (C-IgA) and C4 (C-C4) change values between the first and second biopsies were independent risk factors for LFP. IgA levels increased, and C4 levels decreased during the second liver puncture. The remaining 1,806 patients received one liver puncture (group 2). They were divided into the following subgroups: A (F≤1), B (1<F≤3), and C (F>3) to verify whether the same trend was observed by cross-sectional study. IgA levels were highest, and C4 levels were lowest in group C (IgA: C>B>A, p<0.05; C4: C<B<A, p<0.05). The findings of this study suggest that serum IgA and C4 levels are independent risk factors for LFP that could serve as future targets for L.F. management and treatment.

Prevalence of neurological diseases among patients with selective IgA deficiency.

Background: There are no published epidemiologic studies with regard to the prevalence of neurologic diseases among subjects with selective immunoglobulin A (IgA) deficiency (sIgAD). Objective: To investigate the prevalence of neurologic diseases among the Israeli population with sIgAD. Methods: A population-based case-control study among members of a large nationwide health maintenance organization in Israel providing services to > 700,000 members. The sIgAD group included individuals ≥4 years of age with a serum IgA level of <0.07 g/L and with a diagnosis of sIgAD. The control group was randomly sampled from the entire study population with a case-control ratio of five controls for each case (1:5), with exact matching for age, gender, ethnic group, and socioeconomic status category. Results: A total of 796 subjects ages 20.58 ± 15.46 years; 391 female subjects (49.1%) were identified as having sIgAD. The control group was constituted of 3980 matched subjects. The sIgAD group was characterized by a higher prevalence of autism spectrum disorder and tic disorders. Migraine was less prevalent in the sIgAD group (19 [2.39%]) than in the control group (168 [4.22%]), odds ratio (OR) 0.55 (95% confidence interval {CI}, 0.34-0.90); p = 0.016]. More cases of subjects with epilepsy were observed in the sIgAD group (14 [1.76%]) than in the control group (31 [0.80%]), OR 2.28 (95% CI, 1.12 - 4.44; p = 0.015). Conclusion: Our observation raises the question of the role of IgA in noninfectious diseases of the central nervous system. Further basic studies are needed to explain our observation.

Elevated Total Serum Immunoglobulin A Levels in Patients with Suspicion for Celiac Disease.

Patients with classic symptoms of celiac disease are often initially tested for serum tissue transglutaminase-immunoglobulin A (tTG-IgA) and total serum immunoglobulin A (IgA) levels concurrently, as IgA deficiency can lead to falsely low tTG-IgA. There are no guidelines for incidental findings of elevated total serum IgA when testing for celiac disease. In our study, we described the proportion of patients with suspicion of celiac disease who had elevated total serum IgA and the factors that may be associated with these findings. We studied the management of these patients with incidental findings of elevated total serum IgA to identify its clinical significance. To investigate, we performed a retrospective chart review of patients who underwent celiac disease serologic testing at a single clinic from January 2017 to June 2022. We reported further laboratory workup and follow-up for patients with incidental findings of elevated total serum IgA by board-certified immunologists. In our chart review, 848 patients were identified, 85 (10.0%) of whom were found to be negative for celiac disease but had elevated total serum IgA levels (median IgA 351 mg/dL, interquartile range 324-382). Out of 85 patients, 73 were further evaluated by immunologists, with 55 patients undergoing additional laboratory workup. None were diagnosed with specific immunologic conditions. Male sex was identified as associated with elevated total serum IgA findings, and constipation was found in a statistically significant greater frequency of patients with normal total serum IgA rather than elevated total serum IgA. To provide external validation of our findings, we created a second patient cohort within the Stanford Research Repository database. Out of 33,875 patients identified, a similarly high proportion of patients were negative for celiac disease but had elevated total serum IgA levels (9.3%, 3140 patients). In this separate patient cohort, male sex was also identified as being associated with elevated total serum IgA. Our study also provides preliminary evidence that patients with incidental findings of elevated total serum IgA may not need further management or workup, as these abnormalities may not be clinically relevant without other clinical suspicions.

Efficacy of Electroacupuncture with Sparse-Dense-Wave on Patients Suffered Acute Facial Paralysis.

To explore the efficacy of electroacupuncture (EA) with sparse-dense wave form on the improvement of facial nerve edema, facial spasm, and repair of nerve injury in patients with acute facial paralysis. This study enrolled 100 patients who were treated for acute facial paralysis in People's Hospital of Dongxihu District from December 2019 to December 2020. They were randomly divided into the control group (continuous wave) and the sparse-dense wave group (sparse-dense wave), following by being intervened by EA with different wave forms. Then the facial disability index (FDI) score, serum levels of immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) in the two groups were evaluated. The total effectiveness rate (98.00% and 86.00%, respectively; P < 0.05) and the recovery rate of facial spasm (76.00% and 56.00%, respectively; P<0.05) in the sparse-dense wave group was both significantly higher than that of the control group. After treatment, the scores of physical functions of patients in both groups increased (P < 0.05), the scores of social/well-being dysfunctions decreased (P < 0.05). Besides, the levels of serum IgA, IgG, and IgM in both groups decreased (P < 0.05), and the serum levels in the sparse-dense wave group were significantly lower than the control group (P < 0.05). EA intervention with sparse-dense wave form is effective for patients with acute facial paralysis, in that it effectively reduced the occurrence of facial spasm and promoted the improvement of edema and repair of nerve injury.

Serum immunoglobulin A (IgA) levels in children affected with Juvenile Idiopathic Arthritis

Background and objectiveImmunoglobulin A (IgA) is the most abundant antibody isotype in the human body, considering its presence on the mucosal surfaces, in addition to the amount circulating in the bloodstream. Serum IgA levels can be variably altered in several pathological settings. However, very few studies specifically investigated serum IgA in Juvenile Idiopathic Arthritis (JIA). In the present study, we specifically assessed serum IgA levels in our cohort of patients affected with JIA. MethodsIn this cross-sectional study, serum IgA levels were measured in patients with JIA (and age-matched controls) and analyzed according to age class. The correlation of serum IgA levels with hematological, inflammatory, and disease activity parameters was assessed. ResultsNo significant difference in the frequency of low IgA levels (according to the definition of complete and partial IgA deficiency) was observed between JIA patients and controls, overall. This pediatric study population showed a progressive increase of total serum IgA concentrations with age, as expected; however, in JIA patients aged 10–17 years, total IgA serum levels resulted to be significantly higher than in age-matched control subjects. No clear correlation between IgA levels and the examined inflammatory, hematological, and disease activity parameters was observed in JIA patients, except for the erythrocyte sedimentation rate (ESR) in oligoarticular JIA patients: here, serum IgA levels showed a positive and moderate covariation with ESR, which was also observed for disease activity (JADAS-10) in selected oJIA patients without biological therapy. ConclusionsIn our cohort of JIA patients, total serum IgA levels were not reduced and were actually increased in adolescents compared to controls. Larger studies are needed to confirm this finding, which cannot be certainly explained based on the available data in this study, even though JIA disease control and/or chronic inflammation may be implicated to some extent.

High serum IgA levels inpatients with IgG4-related disease are associated with mild inflammation, sufficient disease-specific features, andfavourable responses to treatments.

Although elevated serum immunoglobulin A (IgA) levels are thought to exclude a diagnosis of IgG4-related disease (IgG4-RD), IgG4-RD has been definitively diagnosed in some patients despite elevated serum IgA levels. This study aimed to clarify the prevalence of elevated IgA levels in patients with IgG4-RD and to compare the clinical features of IgG4-RD patients with and without elevated IgA levels. The clinical features of 169 IgG4-RD patients were retrospectively compared among those with and without elevated serum IgA levels. Of the 169 patients with IgG4-RD, 17 (10.1%) had elevated serum IgA levels. Those with elevated serum IgA levels showed higher serum C-reactive protein levels and lower prevalence of relapse than those without. Other clinical features did not differ significantly, including inclusion scores of the American College of Rheumatology/European League Against Rheumatism classification criteria. Cox regression analysis showed that elevated serum IgA levels were associated with a lower incidence of relapse. Moreover, patients with elevated serum IgA levels showed prompt improvement in response to glucocorticoids in the IgG4-RD responder index. Some patients diagnosed with IgG4-RD have high serum IgA levels. These patients may form a subgroup, characterized by good response to glucocorticoids, less frequent relapse, mildly elevated serum C-reactive protein levels, and possible complications of autoimmune diseases.

A study to estimate the serum IgA and salivary IgA levels in patients with oral leukoplakia and oral squamous cell carcinoma.

The increasing death rate because of oral cancer is mainly due to its late diagnosis. Tumour markers are often detected in abnormal amounts in blood, urine or saliva of patients with certain types of cancer. Diagnosing cancer through human saliva has advantages such as low invasiveness, minimum cost and easy sample collection. We have used serum immunoglobulin A (IgA) and salivary IgA for our present study. The aim of present study was to estimate serum and salivary IgA levels in oral leukoplakia and oral squamous cell carcinoma (OSCC) patients. The study included 40 patients; 10 in the control group, 15 cases with oral leukoplakia and 15 cases with OSCC. The blood samples and saliva were taken from clinically diagnosed oral leukoplakia and OSCC patients and were tested for IgA levels. The data were analysed using SPSS 16.0. The mean values were compared between the groups by using analysis of variance (ANOVA) followed by post-hoc test for group-wise comparison. P value ≤ 0.05 was considered significant. It was observed that the comparison of levels of serum IgA in control and leukoplakia group; control and OSCC group; leukoplakia and OSCC group were found to be statistically significant. Also, comparison between the levels of salivary IgA in control and OSCC group was found to be statistically significant. It is suggested that the serum and salivary IgA levels could be a better adjuvant diagnostic marker along with routine markers in patients with premalignant and malignant lesions.

Associating Serum IgM, IgA Levels with Thoracic CT Indicators and Pulmonary Function Indexes in Acutely Exacerbated Chronic Obstructive Pulmonary Disease Patients.

Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by acute exacerbations and reduced lung function. This study investigates the link between serum markers (Immunoglobulin M (IgM) and Immunoglobulin A (IgA)), thoracic computed tomography (CT) scan findings, and pulmonary function indexes during these episodes, aiming to improve our understanding and identify new diagnostic indicators. From the First Affiliated Hospital of Hebei North University, we selected 89 COPD patients experiencing acute exacerbation within the past two years for our Acute Exacerbation Group (AG). Meanwhile, 96 COPD patients, initially treated at the same hospital and currently deemed stable, were chosen for the Stable Group (SG). Both groups underwent serum IgM and IgA tests, thoracic CT examinations, and pulmonary function assessments. In the AG Group, the serum IgM levels were marginally lower than in the Stable Group (SG), though the difference wasn't statistically significant (p = 0.097). Conversely, serum IgA levels in the AG were significantly lower than in the SG (p < 0.001). The AG also showed markedly reduced lung volume, inspiratory lung density, and pulmonary function indexes compared to the SG while having considerably higher values for emphysema index (EI) and air trapping index (ATI) (all p < 0.001). Pearson correlation analysis revealed that lung volume, average inspiratory lung density, and IgA levels had strong positive correlations with one-second forced expiratory volume (FEV1), FEV1/forced vital capacity (FVC), and diffuse carbon monoxide (DLCO) (with respective r-values of 0.824, 0.841, and 0.829; all p < 0.001). In contrast, EI and ATI exhibited significantly negative correlations with FEV1, FEV1/FVC, and DLCO (with r-values ranging from -0.837 to -0.885; all p < 0.001). The assessment of serum IgA combined with thoracic CT parameters offers valuable insights for diagnosing and evaluating acute exacerbations of COPD, presenting a straightforward clinical utility.

Effects of Shengjiangsan, white silkworm and Periostracum cicadae on cytokines in Henoch-Schönlein purpura nephritis

Henoch-Schönlein purpura (HSP, also named IgA vasculitis) is a common childhood vascular disease, which is characterized by immunoglobulin A (IgA deposition) in small blood vessels; HSP causes kidney involvement to develop Henoch-Schönlein purpura nephritis (HSPN). However, the exact pathogenesis of HSPN is not fully understood, and it is still necessary to explorer new drugs for the treatment of HSPN. In this study, bovine serum albumin (BSA), lipopolysaccharide (LPS) and carbon tetrachloride (ClC4) were used to induce IgAN in rat, and the blood stasis and heat syndrome model was established concurrently, and was combined to establish the HSPN model. The therapeutic effects of different doses of Shengjiangsan (5, 10, 20 g/kg), white silkworm (1, 2, 4 g/kg), and Periostracum cicadae (0.5, 1, 2 g/kg) on HSPN model rats were studied, then 24 h urine was collected and blood from the abdominal aorta was taken to detect the protein changes in urine and blood. Immunofluorescence staining was used assess to IgA deposition in glomeruli. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and immunoglobulin A (IgA) levels were measured in serum by enzyme-linked immunosorbent assay. Hematoxylin and eosin (H&amp;E) and periodic acid Schiff (PAS), immunohistochemical staining was performed to observe the histopathological changes in kidney tissues. In addition, Western blotting was used to detect the changes in the expression levels of IgA, TNF-α, and toll-like receptor 4 (TLR4). In the results, Shengjiangsan, white silkworm, and Periostracum cicadae could significantly reduce the levels of urine protein, blood urea nitrogen (BUN) and serum creatinine (CREA) in HSPN rats. Serum levels of IgA, TNF-α, IL-1β, and IL-6 were significantly reduced in the treatment groups. The treatment group can effectively improve renal tissue inflammation and mesangial hyperplasia. The accumulation of IgA protein in renal tissue was significantly reduced in the treatment group. The expression of monocyte chemoattractant protein (MCP)-1, TLR4, and IgA were significantly reduced and responded in a dose-dependent manner. Moreover, levels of transforming growth factor beta 1 (TGF-β1) decreased in kidney tissues in the treatment groups. In conclusion, Shengjiangsan, white silkworm, and Periostracum cicadae could improve HSPN in rats by reducing renal inflammation and fibrosis, and the therapeutic effects of white silkworm and Periostracum cicadae were slightly better than Shengjiangsan.

Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits

Immunoglobulin A (IgA) mediates mucosal responses to food antigens and the intestinal microbiome and is involved in susceptibility to mucosal pathogens, celiac disease, inflammatory bowel disease, and IgA nephropathy. We performed a genome-wide association study of serum IgA levels in 41,263 individuals of diverse ancestries and identified 20 genome-wide significant loci, including 9 known and 11 novel loci. Co-localization analyses with expression QTLs prioritized candidate genes for 14 of 20 significant loci. Most loci encoded genes that produced immune defects and IgA abnormalities when genetically manipulated in mice. We also observed positive genetic correlations of serum IgA levels with IgA nephropathy, type 2 diabetes, and body mass index, and negative correlations with celiac disease, inflammatory bowel disease, and several infections. Mendelian randomization supported elevated serum IgA as a causal factor in IgA nephropathy. African ancestry was consistently associated with higher serum IgA levels and greater frequency of IgA-increasing alleles compared to other ancestries. Our findings provide novel insights into the genetic regulation of IgA levels and its potential role in human disease.

Serologic Response of SARS-CoV-2 mRNA-based Vaccines in Patients with Autoimmune Diseases

Background: In the spring of 2021, coronavirus disease 2019 (COVID-19) vaccines were approved and distributed in the United States for the public to combat the COVID-19 pandemic, but their rapid development leaves some questions unanswered. Vaccine efficacy has always been a point of interest for individuals with rheumatological diseases that take immunosuppressants. This study investigates the vaccine efficacy of two COVID-19 mRNA-based vaccines, Moderna and Pfizer, in subjects in West Texas patients with autoimmune diseases. Materials and Methods: Blood was collected from Texas Tech University employees who received both doses of COVID-19 vaccines within the past nine months. Subjects were separated into either a group with a known history of rheumatic disease (n=18) or those without (n=18). The samples were analyzed for serum immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels using specific enzyme-linked immunoassay kits, and a neutralizing antibody test using a surrogate virus was conducted as well. Results were analyzed using the Mann-Whitney U test (unpaired, two-tailed). Results: There was no significant difference in serum IgG and IgA levels between the control and rheumatologic disease groups, but there were significant differences in serum IgM levels. All subjects cleared the threshold for the neutralizing antibody test. Conclusion: The relatively similar serum IgG levels and the 100% detection rate of effective neutralizing antibodies across both groups indicate promising signs of serological response for subjects with autoimmune conditions, but the relatively low serum IgA and IgM levels of the study the group warrants further investigation.

Relationship between Selective IgA Deficiency and COVID-19 Prognosis.

The prevalence and mortality rates of coronavirus disease 2019 (COVID-19) widely vary among populations. Mucosal immunity is the first barrier to the pathogen's entry into the body. Immunoglobulin A (IgA) is the primary antibody responsible for mucosal immunity. We explored the relationship between selective IgA deficiency (SIgAD) and COVID-19 severity. We included 424 patients (203 women) with COVID-19. Eleven patients had SIgAD. Laboratory data of patients with SIgAD and normal IgA levels were compared. The relationship between SIgAD and severe COVID-19 infection was explored using logistic regression analysis. In the univariate logistic regression analysis, the risk of severe COVID-19 disease in patients with SIgAD was approximately 7.7-fold higher than that in other patients (odds ratio [OR], 7.789; 95% confidence interval [CI], 1.665-36.690, P = 0.008), while it was 4-fold (OR, 4.053; 95% CI, 1.182-13.903, P = 0.026) higher in the multivariate logistic regression analysis. Serum IgA levels were positively correlated with total lymphocyte counts and negatively correlated with C-reactive protein levels, which was a risk factor for severe COVID-19. In patients with SIgAD, the number of severe acute respiratory coronaviruses 2 that pass through mucosal membranes may be increased, leading to complications such as cytokine storm syndrome and acute respiratory distress syndrome.

The Probiotic Strain Bifidobacterium animalis ssp. lactis HY8002 Potentially Improves the Mucosal Integrity of an Altered Intestinal Microbial Environment.

Intestinal microbiota mediate the development and regulation of the intestinal immune system either directly or indirectly. Particularly, Bifidobacterium spp. play an important role in regulating the intestinal immunity and intestinal barrier. We demonstrated that Bifidobacterium animalis ssp. lactis HY8002, selected from eight Bifidobacterium strains by in vitro experimentation, had exceptional resistance to digestive tract conditions and high adhesion to intestinal epithelial cells and a positive effect on immunoglobulin A (IgA) secretion by Peyer’s patch cells. Moreover, HY8002 restored the expression of tight junction-related genes, initially reduced by lipopolysaccharide treatment, to normal levels in human intestinal epithelial cells. Notably, HY8002 restored kanamycin-induced reduction in Peyer’s patch cell numbers, serum and fecal IgA levels, and zonula occludens 1 and Toll-like receptor 2 levels in the mouse small intestine. In addition, HY8002 restores microbiome composition disturbed by kanamycin, and these microbiome changes have been found to correlate with TLR2 levels in the small intestine. Moreover, the ability of HY8002 to enhance IgA in Peyer’s patch cells and ZO-1 levels in intestinal epithelial cells was significantly inhibited by a TLR2 blocking antibody, which suggests that the HY8002 improve intestinal barrier function via TLR2. Finally, whole-genome sequencing of HY8002 revealed that it did not possess any known virulence factors. Therefore, HY8002 is a promising, functional probiotic supplement to improve intestinal barrier function by improving intestinal immunity and microbiota balance.