Serum IgA Research Articles

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.

Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia.

Patients with chronic lymphocytic leukemia (CLL) are vulnerable to coronavirus disease 2019 (COVID-19) and are at risk of inferior response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, especially if treated with the first-generation Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. We aimed to evaluate the impact of the third-generation BTKi, zanubrutinib, on systemic and mucosal response to SARS-CoV-2 vaccination. Nine patients with CLL with ongoing zanubrutinib therapy were included and donated blood and saliva during SARS-CoV-2 vaccination, before vaccine doses 3 and 5 and 2 - 3 weeks after doses 3, 4, and 5. Ibrutinib-treated control patients (n = 7) and healthy aged-matched controls (n = 7) gave blood 2 - 3 weeks after vaccine dose 5. We quantified reactivity and neutralization capacity of SARS-CoV-2-specific IgG and IgA antibodies (Abs) in both serum and saliva, and reactivity of T cells activated with viral peptides. Both zanubrutinib- and ibrutinib-treated patients had significantly, up to 1,000-fold, lower total spike-specific Ab levels after dose 5 compared to healthy controls (P < 0.01). Spike-IgG levels in serum from zanubrutinib-treated patients correlated well to neutralization capacity (r = 0.68; P < 0.0001) and were thus functional. Mucosal immunity (specific IgA in serum and saliva) was practically absent in zanubrutinib-treated patients even after five vaccine doses, whereas healthy controls had significantly higher levels (tested in serum after vaccine dose 5) (P < 0.05). In contrast, T-cell reactivity against SARS-CoV-2 peptides was equally high in zanubrutinib- and ibrutinib-treated patients as in healthy control donors. In our small cohort of zanubrutinib-treated CLL patients, we conclude that up to five doses of SARS-CoV-2 vaccination induced no detectable IgA mucosal immunity, which likely will impair the primary barrier defence against the infection. Systemic IgG responses were also impaired, whereas T-cell responses were normal. Further and larger studies are needed to evaluate the impact of these findings on disease protection.

Umbilical Cord Blood IgA Levels and Bacterial Profile in Preterm Neonates Born with Maternal Risk Factors for Early-Onset Neonatal Sepsis.

To investigate the IgA levels and bacterial profile in umbilical cord blood (UCB) samples of mothers with risk factors compared to those without risk factors; and to understand the link between UCB culture positivity and neonatal outcomes [early-onset sepsis (EOS) or death within 7 d of life]. This is a pilot prospective case-control study. Mothers with preterm deliveries (gestational age <34 wk) were enrolled in two groups- Cases: Those with antenatal risk factors (prolonged duration of rupture of membranes of ≥24h or chorioamnionitis) and controls: Those without these two risk factors. Serum IgA levels was assayed and microbiological culture was tested in UCB samples. 16S sequencing to determine the UCB microbiome was performed in a subset of samples (n = 15). Neonates were followed-up for the occurrence of EOS or death until 7 d of life. Forty-nine mothers as cases and 50 mothers as controls were consecutively enrolled. No significant difference was observed in the IgA levels (60.5 vs. 58.1mg/L; p = 0.71), neonatal blood culture positivity (4.1% vs. 8.0%; p = 0.41) and UCB culture positivity (30.6% vs. 26.0%; p = 0.61) in the two groups.No difference was observed between the groups in occurrence of EOS or death within 7 d of life. Proteobacteria, Firmicutes and Actinobacteria were the most abundant phyla. Serratia, Bifidobacterium, Collinsella, Meganomas and Blautia being the most common genera. Cord blood IgA concentration could not differentiate the neonates at-risk of infection due to its presence in both the groups.

The effects of music in cardiac surgery patients: early results

Abstract Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): Sundry fund to Massachusetts General Hospital. Background/Significance Research into the health benefits of music has expanded, driven by a desire to see how it can be better applied in healthcare. There has been an interest in the chemical and biological biomarkers of music. Most studies have focused on physical, and psychological findings. There have been few systematic studies that consider the parallel psychological, physical, and biological effects of music in cardiac surgical patients. Purpose The purpose of this study is to measure psychological, physiological, and biological responses to a music intervention compared to standard of care in cardiac surgical patients. The primary outcome is serum cortisol levels pre and post a 30-minute music intervention compared to the standard of care group. The secondary outcomes are state anxiety, pain, blood pressure, heart rate, respirations, and serum Immunoglobulin A (IgA). Methods This is a randomized, placebo-controlled, pre/post clinical trial to compared responses to the study intervention of music versus standard of care. Psychological responses were measured for anxiety by the Spielberger State Anxiety Scale, and pain by a visual analogy scale, physical responses were measured by blood pressure, heart rate, and respirations, and the biologic markers were measured by serum cortisol and IgA. Results Sixty-three patients were approached, 14 were excluded and 25 declined participation. Most patients who declined stated that they did not feel well enough to participate or did not want more blood samples taken. There were 20 subjects, 15 males and 5 females, mean age of 58.8 years, who did participate. The groups were similar on demographics and pre intervention outcome measures. There was no difference between standard of care and treatment group in the primary outcome, serum cortisol levels (17.8+7.4 vs 15.6+7.6) and no differences in the secondary outcomes post the intervention period. Conclusions This is the early results of a study on use of music as a nursing intervention in cardiac surgery patients. Subject enrollment will continue to provide evidence of the benefits for patients after cardiac surgery. Implications for Nursing Practice Nurses are poised to provide the evidence for non-pharmacological interventions to enhance the patient experience after cardiac surgery.

Effect of Immune Plasma Therapy on Mortality and Morbidity in Patients with Covid-19: A Retrospective Study

Objective: Immune plasma therapy, a method employed for passive immunization, has been utilized as a treatment modality based on historical precedents during the Covid-19 pandemic, a global crisis resulting in the unfortunate demise of countless individuals. The objective of this study is to investigate the impact of immune plasma therapy on laboratory parameters and the overall survival rate in patients with Covid-19 pneumonia. Material and Methods: Our study was designed as a retrospective analysis, conducted at a tertiary healthcare institution from April 1, 2020, to December 31, 2020. The study population comprised individuals aged 18 and above, presenting with pulmonary involvement, and diagnosed with Covid-19 using the polymerase chain reaction (PCR) method at our hospital. The inclusion criteria encompassed patients who received immune plasma therapy, as well as a control group matched for age, gender, and admission date, who did not undergo immune plasma therapy. Exclusion criteria involved patients with low serum IgA levels, those who did not provide consent for immune plasma therapy, and individuals below the age of 18. Results: The study comprised a total of 72 patients who received immune plasma therapy and 72 patients in the control group, matched for age and gender, all diagnosed with Covid-19. The median age of the patients was 70 years, ranging from 19 to 91, and 56.9% (41) of them were female. When comparing the immune plasma group with the control group, several significant differences were observed (p&lt;0.05). These included elevated levels of leukocytes, neutrophils, neutrophil-lymphocyte ratio (NLR), glucose, aspartate aminotransferase (AST), sedimentation rate, C-reactive protein (CRP), ferritin, fibrinogen, d-dimer, and low levels of platelets and lymphocytes in the control group. Furthermore, in the immune plasma therapy group, significant associations were found between mortality and lymphocyte count, NLR, AST, CRP, and d-dimer elevation after treatment (p&lt;0.05). Additionally, pre- and post-treatment measurements of troponin, procalcitonin, and ferritin were significantly correlated with mortality (p&lt;0.05). Conclusion: The administration of immune plasma therapy, involving the transfer of neutralizing antibodies, has demonstrated a favorable impact on laboratory parameters and overall survival in severe cases of Covid-19 pneumonia, particularly during the early stages of the disease.

Effect of hematuria on the kidney disease progression in IgA nephropathy patients with mild proteinuria and well-preserved renal function

ObjectiveTo investigate whether hematuria is a risk factor in IgA nephropathy (IgAN) patients with mild proteinuria and well-preserved renal function. MethodsThis retrospective study included a total of 63 IgAN patients, with complete clinical data available for 50 patients. Hematuria assessment was conducted using two methods: 1) an automated method using a urine particle analyzer, and 2) a manual method performed by a skilled examiner to examine microscopic urine sediment. ResultsThe results of hematuria measurement using both automated and manual methods showed a strong linear correlation (r = 0.78, P < 0.001). In IgAN patients, those with high urinary red blood cell count (U-RBCs) exhibited higher serum IgA levels compared to patients with low U-RBCs. Additionally, patients with crescent formation had higher levels of proteinuria compared to those without crescents. Patients who received immunosuppressive treatment displayed higher levels of systolic blood pressure (SBP) and mean arterial pressure (MAP), as well as lower levels of serum hemoglobin and albumin. They also had a higher prevalence of T1 lesions compared to patients who did not undergo immunosuppression. Furthermore, among patients with crescent formation, those who received immunosuppressive agents exhibited higher levels of SBP, diastolic blood pressure (DBP), MAP, and U-RBCs, as well as lower levels of albumin and proteinuria at the time of renal biopsy. No composite kidney endpoint events were observed in these groups of patients. The U-RBCs level was not identified as a risk factor influencing the decline of estimated glomerular filtration rate (eGFR) in IgAN. ConclusionsThe presence of hematuria at the time of biopsy was not found to be associated with kidney disease progression in IgAN patients who had mild proteinuria and well-preserved renal function. This suggests that it is possible that these patients may not derive significant benefits from immunosuppressive therapy.

Significance of Anti-COVID-IgA antibody response in COVID-19 breakthrough infection in vaccinated patients - a single-centered study from Pakistan.

An increasing number of breakthrough-COVID-19-vaccinated individuals are being reported across the world. Humoral immunity has a crucial role in combating infection. In this study, we aimed to assess the importance of anti-COVID-S1-IgA and anti-COVID-NP-IgA in confirmed COVID-19 after vaccination (breakthrough infection group). Blood samples were collected from the breakthrough infection group within one week of breakthrough infections (n = 34). A second sample was also collected after 4 to 8 weeks (n = 27). Blood samples of healthy individuals (n = 29) were collected 4-8 weeks after the completion of vaccination. Anti-COVID-S1-IgA and anti-COVID-NP-IgA were detected by ELISA. Statistical analysis was performed using IBM SPSS version 24. In this study, we found a higher positivity rate for anti-COVID-S1-IgA in the breakthrough infection group (70% vs. 28% in healthy individuals). Anti-COVID-NP-IgA was not found in the control group (11% in the breakthrough infection group vs. 0 in healthy individuals). In the breakthrough-infected group, the positivity rate of anti-COVID-NP-IgA decreased significantly (median titers 16.9 IU/ml decreased to 4.2 IU/ml) p = 0.001), while anti-COVID-S1-IgA increased over a period of 4-8 weeks (9.35-16.35 IU/ml). Importantly, IgA response to both COVID-19 NP and S1 antigens was not found in 13 patients at initial testing. The findings of this study show that serum IgA may have a role both in breakthrough infections and also in the prevention of severe infection. Sluggish anti-COVID-19-IgA antibody response may be responsible for the occurrence of COVID-19 infection in breakthrough infection. On the other hand, more sustained anti-COVID-19-S1-IgA over a longer period of time may have a role in preventing these patients from severe infections and hospitalization. However, a study on a larger sample size including patients with severe disease after vaccination is required to prove this hypothesis. To the best of our knowledge, this is the first study reporting the importance of serum IgA in breakthrough-infected patients from our region.

Unveiling a New Perspective on Distinguishing Omicron Breakthrough Cases and Postimmune COVID-19-Naive Individuals: Insights from Antibody Profiles.

In the situation of mass vaccination against COVID-19, few studies have reported on the early kinetics of specific antibodies (IgG/IgM/IgA) of vaccine breakthrough cases. There is still a lack of epidemiological evidence about the value of serological indicators in the auxiliary diagnosis of COVID-19 infection, especially when the nucleic acid results were undetectable. Omicron breakthrough cases post-inactivated vaccination (n = 456) and COVID-19-naive individuals with two doses of inactivated vaccination (n = 693) were enrolled. Blood samples were collected and tested for SARS-CoV-2 antibody levels based on the magnetic chemiluminescence enzyme immunoassay. Among Omicron breakthrough cases, the serum IgG antibody level was 36.34 Sample/CutOff (S/CO) (95% confidence interval [CI], 31.89 to 40.79) in the acute phase and 88.45 S/CO (95% CI, 82.79 to 94.12) in the recovery phase. Serum IgA can be detected in the first week post-symptom onset (PSO) and showed an almost linear increase within 5 weeks PSO. Compared with those of breakthrough cases, IgG and IgA titers of the postimmune group were much lower (4.70 S/CO and 0.46 S/CO, respectively). Multivariate regression showed that serum IgG and IgA levels in Omicron breakthrough cases were mainly affected by the weeks PSO (P < 0.001). Receiver operating characteristic ROC0 curve analysis showed that the area under the curve (AUC) was 0.744 and 0.806 when the cutoff values of IgA and IgG were 1 S/CO and 15 S/CO, respectively. Omicron breakthrough infection can lead to a further increase in IgG and IgA levels relative to those of the immunized population. When nucleic acid real-time PCR was negative, we would use the kinetics of IgG and IgA levels to distinguish the breakthrough cases from the immunized population. IMPORTANCE This study fills a gap in the epidemiological evidence by investigating the value of serological indicators, particularly IgG and IgA levels, in the auxiliary diagnosis of COVID-19 infections when nucleic acid results are undetectable. The findings reveal that among Omicron breakthrough cases, both IgG and IgA antibody levels exhibit significant changes. Serum IgG levels increase during the acute phase and rise further in the recovery phase. Serum IgA can be detected as early as the first week post-symptom onset (PSO), showing a consistent linear increase within 5 weeks PSO. Furthermore, receiver operating characteristic (ROC) curve analysis demonstrates the potential of IgG and IgA cutoff values as diagnostic markers. The study's conclusion underscores the importance of monitoring IgG and IgA kinetics in distinguishing Omicron breakthrough cases from vaccinated individuals. These findings contribute to the development of more accurate diagnostic approaches and help inform public health strategies during the ongoing COVID-19 pandemic.

Development of Chimeric Hepatitis B (HBV) – Norovirus (NoV) P particle as candidate vaccine against Hepatitis B and norovirus infection

IntroductionHepatitis B remains a global problem with no effective treatment. Here, a mucosal vaccine candidate was developed with HBsAg and HBcAg, to provide both prophylactic and therapeutic protection against hepatitis B. The antigens were presented using the P particle of human norovirus (HuNov). As a result, the chimeric HBV – HuNoV P particle can act as a dual vaccine for hepatitis B and HuNoV. MethodsThe vaccine candidate was expressed and purified from Escherichia coli BL21 (DE3) cells. HBV-HuNoV chimeric P particles were successfully expressed and isolated, with sizes of approximately 25.64 nm. Then, the HBV-HuNoV chimeric P particles were evaluated for safety and immunogenicity in mice and gnotobiotic (Gn) pigs. After three doses (5 µg/dose in mice and 200 µg/dose in Gn pigs) of intranasal immunization, humoral and cellular immune responses, as well as toxicity, were evaluated. ResultsThe vaccine candidate induced strong HBV-HuNoV specific IFN-γ producing T-cell responses in the ileum, spleen, and blood of Gn pigs. Serum IgG and IgA antibodies against HBV-HuNoV chimeric P particles also increased significantly in Gn pigs. Increased HBsAg- and HuNoV-specific serum IgG responses were observed in mice and Gn pigs, although not statistically significant. The vaccine candidate did not show any toxicity in mice. ConclusionsIn summary, the chimeric HBV-HuNoV P particle vaccine given intranasally was safe and induced strong cellular and humoral immune responses in Gn pig. Modifications to the vaccine structure and dosage need to be evaluated in future studies to further enhance immunogenicity and induce more balanced humoral and cellular responses.

Effect of a probiotic formula on gastrointestinal health, immune responses and metabolic health in adults with functional constipation or functional diarrhea.

Our aim was to determine the efficacy of four-week probiotic supplementation on gastrointestinal health. The secondary objectives were to assess probiotic effects on immune reaction, as well as weight control and metabolic health. We conducted two randomized sub-trials, respectively, among subjects who were diagnosed with functional constipation (FC) or functional diarrhea (FDr) according to the Rome IV criteria. In each sub-trial, 70 eligible Chinese adults were randomized to receive a multi-strain probiotic combination or a placebo. Gastrointestinal symptoms, defecation habits, stool characteristics, blood and fecal biochemistry markers, anthropometrics measures, stress-associated responses, and intestinal flora changes were assessed at baseline and after probiotics intervention. Four weeks of probiotic supplementation reduced overall gastrointestinal symptoms scores in FC participants (p < 0.0001). Their mean weekly stool frequency increased from 3.3 times to 6.2 times; immune response and inflammation markers improved with increases in serum IgA, IFN-γ and fecal sIgA, and decrease in hsCRP; most components of lipid profile were significantly ameliorated, with increases in HDL-C and reductions in TC and TG; body weight, body mass index and basal metabolic rate decreased following probiotics consumption. For FDr participants, probiotics consumption markedly reduced overall gastrointestinal symptom scores (p < 0.0001); decreased stool frequency by 3 times per week; increased IgA, IFN-γ, sIgA concentrations, while lowered hsCRP and IL-4 levels. Both FC and FDr participants had improvement in the scores of defecation habits, anxiety or depression, and perceived stress. Probiotics supplementation promoted the production of all three major short-chain fatty acids. No changes were observed in LDL-C, IgG, IgM, IL-8, IL-10 and motilin. Supplementation with the probiotic formula over a four-week period could help relieving gastrointestinal symptoms, improving satisfaction with defecation habits, emotional state and immune response, and ameliorating dysbacteriosis in participants with FC or FDr. It also had beneficial effects on lipid metabolism and weight control for FC participants.

Separate Gut Plasma Cell Populations Produce Auto-Antibodies against Transglutaminase 2 and Transglutaminase 3 in Dermatitis Herpetiformis.

Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extra intestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are auto-antibodies to transglutaminase 2 (TG2) and transglutaminase 3 (TG3), respectively. DH patients have auto-antibodies reactive with both transglutaminase enzymes. Here it is reported that in DH both gut plasma cells and serum auto-antibodies are specific for either TG2 or TG3 with no TG2-TG3 cross reactivity. By generating monoclonal antibodies from TG3-specific duodenal plasma cells of DH patients, three conformational epitope groups are defined. Both TG2-specific and TG3-specific gut plasma cells have few immunoglobulin (Ig) mutations, and the two transglutaminase-reactive populations show distinct selection of certain heavy and light chain V-genes. Mass spectrometry analysis of TG3-specific serum IgA corroborates preferential usage of IGHV2-5 in combination with IGKV4-1. Collectively, these results demonstrate parallel induction of anti-TG2 and anti-TG3 auto-antibody responses involving separate B-cell populations in DH patients.

Secretory IgA as Biomarker for Gastrointestinal Nematodes Natural Infection in Different Breed Sheep.

Specific IgA antibody has been shown to play an important role in resistance to gastrointestinal nematode (GIN) infections in sheep, particularly in Teladorsagia circumcincta parasitosis. In some breeds, negative associations have been shown between IgA levels and worm burden in experimentally infected sheep. In the present study, we have studied the relationship between IgA levels in naturally infected sheep (582 ewes in total; 193 younger than one year old and 389 older than one year old) and fecal egg count (FEC) in the Assaf, Castellana, and Churra breeds. ELISA assays were performed to measure IgA levels against the somatic antigen of T. circumcincta third larval stage (L3) and a 203-amino-acid fragment of the protein disulfide isomerase from the same GIN species. A multilevel random intercept model was developed to predict the infection risk according to age or breed. Spearman's correlation rank was used for statistical analysis. The prediction model showed that breed was not an influential factor in this study, although the Assaf breed could be considered slightly more susceptible than the others. In addition, age affected the infection risk, with the young ewes more susceptible to infection than the adult groups, except for the Castellana breed, whose risk of infection was similar at all ages. The most significant positive association was found between FEC and IgA measured in the nasal secretions of young ewes using both antigens (Rho = 0.5; p = 0.00); the correlation of FEC with IgA in serum was moderately significant (Rho = 0.306; p = 0.00). Comparing both antigens, the protein disulfide isomerase antigen was less reactive than the somatic antigen from L3. In conclusion, under natural conditions, specific IgA against GIN was positively associated with FEC in sheep, with nasal secretions from young animals being the sample where this association is stronger, which, therefore, could be used as a marker of infection in further studies.

Effect of replacing inorganic iron with iron-rich microbial preparations on growth performance, serum parameters and iron metabolism of weaned piglets.

This study aimed to investigate the effects of replacing of dietary inorganic iron with iron-rich Lactobacillus plantarum and iron-rich Candida utilis on the growth performance, serum parameters, immune function and iron metabolism of weaned piglets. Fifty-four 28-day-old healthy Duroc × Landrace × Yorkshire castrated male weanling piglets of similar body weight were randomly and equally divided into three groups. The piglets were kept in three pens per group, with six pigs in each pen. The dietary treatments were (1) a basal diet + ferrous sulfate preparation containing 120mg/kg iron (CON); (2) a basal diet + iron-rich Candida utilis preparation containing 120mg/kg iron (CUI); and (3) a basal diet + iron-rich Lactobacillus plantarum preparation containing 120mg/kg iron (LPI). The entire feeding trial lasted for 28 days, after which blood, viscera, and intestinal mucosa were collected. The results showed no significant difference in growth parameters and organ indices of the heart, liver, spleen, lung, and kidney of weaned piglets when treated with CUI and LPI compared with the CON group (P > 0.05). However, CUI and LPI significantly reduced the serum contents of AST, ALP, and LDH (P < 0.05). Serum ALT content was significantly lower in the LPI treatment compared to the CON group (P < 0.05). Compared to CON, CUI significantly increased the contents of serum IgG and IL-4 (P < 0.05), and CUI significantly decreased the content of IL-2. LPI significantly increased the contents of serum IgA, IgG, IgM and IL-4 (P < 0.05), while LPI significant decreased the levels of IL-1β, IL-2, IL-6, IL-8, and TNF-α compared to CON (P < 0.05). CUI led to a significant increase in ceruloplasmin activity and TIBC (P < 0.05). LPI significantly increased the contents of serum Fe and ferritin, and increased the serum ceruloplasmin activity and TIBC compared to CON (P < 0.05). Furthermore, CUI resulted in a significant increase in the relative mRNA expression of FPN1 and DMT1 in the jejunal mucosa (P < 0.05). LPI significantly increased the relative mRNA expression of TF, FPN1, and DMT1 in the jejunal mucosa (P < 0.05). Based on these results, the replacement of dietary inorganic iron with an iron-rich microbial supplement could improve immune function, iron absorption and storage in piglets.

MTMR3 risk alleles enhance Toll Like Receptor 9-induced IgA immunity in IgA nephropathy

Multiple genome-wide association studies (GWASs) have reproducibly identified the MTMR3/HORMAD2/LIF/OSM locus to be associated with IgA nephropathy (IgAN). However, the causal variant(s), implicated gene(s), and altered mechanisms remain poorly understood. Here, we performed fine-mapping analyses based on GWAS datasets encompassing 2762 IgAN cases and 5803 control individuals, and identified rs4823074 as the candidate causal variant that intersects the MTMR3 promoter in B-lymphoblastoid cells. Mendelian randomization studies suggested the risk allele may modulate disease susceptibility by affecting serum IgA levels through increased MTMR3 expression. Consistently, elevated MTMR3 expression in peripheral blood mononuclear cells was observed in patients with IgAN. Further mechanistic studies invitro demonstrated that MTMR3 increased IgA production dependent upon its phosphatidylinositol 3-phosphate binding domain. Moreover, our study provided the invivo functional evidence that Mtmr3-/- mice exhibited defective Toll Like Receptor 9-induced IgA production, glomerular IgA deposition, as well as mesangial cell proliferation. RNA-seq and pathway analyses showed that MTMR3 deficiency resulted in an impaired intestinal immune network for IgA production. Thus, our results support the role of MTMR3 in IgAN pathogenesis by enhancing Toll Like Receptor 9-induced IgA immunity.

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.

Frequency of dyspeptic symptoms, anxiety, depression and health-related quality of life among patients with chronic gastritis according to Helicobacter pylori CagA and VacA status: a cross-sectional study

Objective — to determine the frequency of dyspeptic symptoms, anxiety and depression and to describe health‑related quality of life in patients with chronic gastritis according to Helicobacter pylori cytotoxin‑associated gene A and vacuolating cytotoxin A status.&#x0D; Materials and methods. This cross‑sectional study included a total of 84 patients with H. pylori‑associated chronic gastritis (CG). Based on H. pylori virulence factors status patients were categorized into 2 groups: 50 patients with the cytotoxin‑associated gene A (CagA) and vacuolating cytotoxin A (VacA)‑positive H. pylori strains (Group 1) and 34 patients with CagA‑ and VacA‑negative H. pylori strains (Group 2). The H. pylori virulence factors were determined by the polymerase chain reaction using paraffin stomach biopsies. Serum IgA and IgG antibodies to CagA and VacA were evaluated by solid‑phase enzyme‑linked immunoabsorbent assay. The Hospital Anxiety and Depression Scale (HADS) was used to identify anxiety disorders and depression. The MOS 36‑Item Short Form Health Survey (SF‑36) questionnaire was used to assess the health‑related quality of life (HRQoL). Statistical analysis was performed using Stata 11 and Statistica 6 software packages.&#x0D; Results. Patients with CagA‑ and VacA‑positive H. pylori strains were more likely to have epigastric pain than patients with CagA‑ and VacA‑negative H. pylori strains (60% vs. 35.3%, p=0.026). No statistical difference was observed between the frequency of epigastric burning, early satiety, and postprandial fullness in both groups (р &gt;0.05). Anxiety and depression were significantly more prevalent in patients with CagA‑ and VacA‑positive H. pylori strains (p=0.041; р=0.032, respectively). Patients of Group 1 had significantly lower HRQoL in the domains of Role‑Physical (50 vs. 75; p=0.0001), Bodily Pain (57.5 vs. 77.5; p=0.0001), General Health (45 vs. 75; p=0.0001), Vitality (55 vs. 80; p=0.0011) and Mental Health (56 vs. 84; p=0.0001).&#x0D; Conclusions. H. pylori CagA and VacA‑positive status is an important factor that may have an impact on the clinical course of H. pylori‑associated gastritis. Higher frequency of epigastric pain, anxiety, and depression, as well as lower health‑related quality of life were observed in patients with CagA‑ and VacA‑positive H. pylori strains.&#x0D;

Elevated levels of enteric IgA in an unimmunised mouse model of Hyper IgM syndrome derived from gut-associated secondary lymph organs even in the absence of germinal centres.

Patients with Human Hyper IgM syndromes (HIGM) developed pulmonary and gastrointestinal infections since infancy and most patients have mutations in the CD40 ligand (CD40L) gene. Most HIGM patients compared to healthy subjects have higher/similar IgM and lower IgG, and IgA serum concentrations but gut antibody concentrations are unknown. CD40L on activated T-cells interacts with CD40 on B-cells, essential for the formation of germinal centres (GCs) inside secondary lymphoid organs (SLOs), where high-affinity antibodies, long-lived antibody-secreting plasma cells, and memory B-cells, are produced. C57BL6-CD40 ligand deficient mice (C57BL6-cd40l -/-), are a model of HIGM, because serum immunoglobulin concentrations parallel levels observed in HIGM patients and have higher faecal IgA concentrations. In mice, TGFβ and other cytokines induce IgA production. To compare and evaluate B-cell populations and IgA-producing plasma cells in peritoneal lavage, non-gut-associated SLOs, spleen/inguinal lymph nodes (ILN), and gut-associated SLOs, mesenteric lymph nodes (MLN)/Peyer´s patches (PP) of unimmunised C57BL6-cd40l -/- and C57BL6-wild-type (WT)mice. Peritoneal lavages, spleens, ILN, MLN, and PP from 8-10 weeks old C57BL6-cd40l -/- and WT mice, were obtained. Organ cryosections were analysed by immunofluorescence and B-cell populations and IgA-positive plasma cell suspensions by flow cytometry. In unimmunised WT mice, GCs were only observed in the gut-associated SLOs, but GCs were absent in all C57BL6-cd40l -/- SLOs. PP and MLN of C57BL6-cd40l -/- mice exhibited a significantly higher number of IgA-producing cells than WT mice. In the spleen and ILN of C57BL6-cd40l- /- mice IgA-producing cells significantly decreased, while IgM-positive plasma cells increased. C57BL6-cd40l -/- B-1 cells were more abundant in all analysed SLOs, whereas in WT mice most B-1 cells were contained within the peritoneal cavity. C57BL6-cd40l -/- B-cells in MLN expressed a higher TGFβ receptor-1 than WT mice. Mouse strains small intestine microvilli (MV), have a similar frequency of IgA-positive cells. Together our results confirm the role of PP and MLN as gut inductive sites, whose characteristic features are to initiate an IgA preferential immune response production in these anatomical sites even in the absence of GCs. IgA antibodies play a pivotal role in neutralising, eliminating, and regulating potential pathogens and microorganisms in the gut.

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.

A Case Report of Hyper-IgM Syndrome Patient with Normal Serum IgA Level

Hyper IgM syndromes are a group of disorders characterized by defective T and B cell interactions resulting in the lack of Immunoglobulin class switching. The most common hyper IgM syndrome is CD40 ligand (CD40L) deficiency. Patients with CD40L deficiency present with recurrent infection, neutropenia, and autoimmunity. These patients typically have absent serum IgA and IgG due to the class switch defect. Here we present a case of CD40L deficiency who presented with oral ulcers, failure to thrive, and recurrent fever. His laboratory evaluation was notable for intermittent neutropenia, elevated IgM (397mg/dl), normal IgA (78mg/dl) and low IgG (51mg/dl). Antibody responses to tetanus and measles were undetectable despite full vaccination. Whole exome sequencing showed a likely pathologic variant in CD40LG (c.674 T&gt;C, p.L225S). This case highlights the importance of considering the diagnosis of hyper IgM syndrome in the appropriate clinical setting, even if the patient has a normal serum IgA level.

Allergic Rhinitis and Other Allergic and Autoimmune Disorders in Children with IgA Deficiency

Background: Selective IgA imunodeficiency is the most frequently occurring primary antibody deficiency. Serum IgA level is decreased or even completly absened, while IgM and IgG antibodies displey normal serum levels. IgA plays an important role in immune protection in the gastrointestinal and respiratory tract. Patients with selective IgA imunodeficiency can be asimptomatic (&gt;50% of cases) and can suffer from recurrent gastointestinal and respiratory infecitions, allergies and autoimmune diseases. Allergic rhinitis (AR) is the most common cause of chronic rhinitis. Characteristic feature of allergic rhinitis is eosinophilic inflammation of the nasal mucosa. Several studied have shown that IgA represents a potent trigger of eosinophil degranulation, while other studies have shown that IgA imunodeficiency is a well-known risk factor for atopy. Objective: Objective of this study was to evaluate the frequency of allergic rhinitis and other allergic and autoimmune disorders in children with IgA immunodeficiency. Methods: The study included 36 children diagnosed with IgA imunodeficiency. The presence of allergic and autoimmune disorders was evaluated by specialist of allergology, immunology, rheumatology and otorhinolaryngology. Results: 22 (71,1%) of children were male and the mean age of the patients was 10.5 years. Among the patients 31 (86,11%) had at least one allergic disease: 20 (55,55%) had asthma, 17 (47,22%) had allergic rhinitis, 6 (16,67%) had atopic dermatitis and 5 (13,89%) had urticaria. 14 (38,89%) had at least one of autoimmune disordes: 8 (22,22%) had reactive arthritis, 5 (13,89%) had juvenile idiopathic arthritis, 2 (5,56%) had Mb Hashimoto and 1 (2,78%) had SLE. Conclusion: This study showed that the main clinical manifestations in patients with IgA deficiency were asthma and allergic rhinitis. Results also show increased frequencies in other allergic and autoimmune diseases, compared to available data from general population.