Gut and respiratory microbiota landscapes in IgA nephropathy: a cross-sectional study.

BACKGROUND: IgA nephropathy (IgAN) is intimately linked to mucosal immune responses, with nasopharyngeal and intestinal lymphoid tissues being crucial for its abnormal mucosal immunity. The specific pathogenic bacteria in these sites associated with IgAN, however, remain elusive. Our study employs 16S rRNA sequencing and machine learning (ML) approaches to identify specific pathogenic bacteria in these locations and to investigate common pathogens that may exacerbate IgAN. METHODS: In this cross-sectional analysis, we collected pharyngeal swabs and stool specimens from IgAN patients and healthy controls. We applied 16SrRNA sequencing to identify differential microbial populations. ML algorithms were then used to classify IgAN based on these microbial differences. Spearman correlation analysis was employed to link key bacteria with clinical parameters. RESULTS: We observed a reduced microbial diversity in IgAN patients compared to healthy controls. In the gut microbiota of IgAN patients, increases in Bacteroides, Escherichia-Shigella, and Parabacteroides, and decreases in Parasutterella, Dialister, Faecalibacterium, and Subdoligranulum were notable. In the respiratory microbiota, increases in Neisseria, Streptococcus, Fusobacterium, Porphyromonas, and Ralstonia, and decreases in Prevotella, Leptotrichia, and Veillonella were observed. Post-immunosuppressive therapy, Oxalobacter and Butyricoccus levels were significantly reduced in the gut, while Neisseria and Actinobacillus levels decreased in the respiratory tract. Veillonella and Fusobacterium appeared to influence IgAN through dual immune loci, with Fusobacterium abundance correlating with IgAN severity. CONCLUSIONS: This study revealing that changes in flora structure could provide important pathological insights for identifying therapeutic targets, and ML could facilitate noninvasive diagnostic methods for IgAN.

Prognosis of IgA nephropathy patient with proteinuria remission by supportive therapy: cohort from screening failed Chinese patients in TESTING study.

BACKGROUND: During the run-in phase of the TESTING study, approximately half of patients with IgA nephropathy (IgAN) were excluded due to proteinuria below 1 g/24 h after intensive supportive therapy. The long-term prognosis of these patients needs further investigation. METHODS: 112 screening failed patients in the TESTING study from 10 centers in China were enrolled in this retrospective study. The prognosis of 88 patients, who were excluded because of proteinuria below 1 g/24 h, was analyzed by Landmark Kaplan-Meier analysis. The composite kidney endpoint was defined by a ≥ 50% reduction in eGFR, ESKD (eGFR <15 mL/min per 1.73 m2), chronic dialysis for at least 6 months, or renal transplantation. RESULTS: In total, 88 patients were excluded due to proteinuria less than 1 g/24 h. During the follow-up, 73/88 (83.0%) patients received renin-angiotensin system blocker. 72/88 (81.8%) had stable proteinuria remission and did not receive immunosuppressive therapy (IST), and 16/88 (18.2%) received IST because of a relapse of proteinuria. Landmark Kaplan-Meier analysis revealed that, the kidney survival from dialysis or composite kidney outcome of these excluded patients with IST was similar to those without IST during the early stages of follow-up (dialysis, before 60 months, p = 0.778; composite kidney outcome, before 48 months, p = 0.862); whereas the risk for dialysis of patients receiving IST was significantly higher than those without IST after 60 months (OR = 11.3, p = 0.03). Similarly, the risk for the composite kidney outcome of patients receiving IST was also significantly higher than those without IST after 48 months (OR = 5.92, p = 0.029). CONCLUSIONS: IgAN patients who maintained a persistent remission of proteinuria after intensive supportive therapy had a much better long-term kidney outcome than those who experienced a relapse of proteinuria and needed IST.

The efficacy of rituximab in the treatment of IgA vasculitis nephritis.

The utility of Rituximab (RTX) for IgA vasculitis nephritis (IgAVN) is not well established. Up to now, we analysed the largest samples of IgAVN patients treated by RTX with a total of 41 retrieved subjects up to December 29, 2023 in the present systematic review. We assessed the clinical profiles, efficacy, and safety of RTX treatments. The present review showed that the renal function tended to be stabilized (P = 1.000) and urinalysis tended to normalize after RTX treatment with no serious adverse events reported. Moreover, 40% (16/40) of patients was freed use of glucocorticoid after RTX administration (P < 0.001). The remission rate was 92.7% (38/41) and complete remission rate was 46.3% (19/41) in IgAVN patients. Interestingly, 76.9% (10/13) of IgAVN child patients achieved complete remission when compared with 32.1% (9/28) of adult patients (P = 0.017). In summary, our results support the benefit of RTX therapy in IgAVN patients, especially children subjects.

Correlation analysis of cofilin-1 with renal prognosis in primary IgA nephropathy.

PURPOSE: The purpose of this study was to investigate the correlation between podocyte related biomarker cofilin-1 and renal function, and explore the value of cofilin-1 in predicting the risk of renal adverse prognosis in IgA nephropathy (IgAN). METHODS: Patients with primary IgAN diagnosed by initial renal biopsy performed in our hospital from January 2019 to February 2022 were included. This study was a prospective cohort study. All IgAN patients were detected the expression of cofilin-1 and other related biomarkers (RhoA, NGAL) in urine by enzyme-linked immunosorbent assay (ELISA) and follow-up at least 6 months. We also collected baseline clinicopathologial data of IgAN. The decreased renal function group was defined as baseline eGFR < 60 ml/min/1.73m2. Logistic and Cox regression model were used to analyze the correlation among cofilin-1 and renal prognosis. RESULTS: 133 IgAN patients were included, with a male-to-female ratio of 1.25:1 and an age of 37.67 ± 13.78 years, as well as an average of eGFR was 71.63 (40.42,109.33) ml/min/1.73m2. 56 patients (42.1%) had decreased renal function at baseline, with the average of eGFR was 34.07 (16.72, 49.21) ml/min/1.73 m2. 12 of which developed to renal adverse prognosis. The average of follow-up time was 22.035 ± 8.992 months. The multivariate regression analysis showed that increased urinary cofilin-1 was an independent risk factor associated with baseline renal function decline and renal adverse prognosis in IgAN patients (P < 0.05). ROC curves showed great efficacy of urinary cofilin-1 levels in diagnosing baseline renal function decline and predicting renal adverse prognosis (the area under the ROC curve was 0.708 and 0.803). CONCLUSION: Cofilin-1 as a novel biomarker of podocyte lesion is closely related to renal function decline in IgAN. Cofilin-1 has certain clinical value in predicting the risk of renal adverse prognosis. Podocyte fusion affects the renal prognosis of IgAN.

Serum IgA antibody level against porcine epidemic diarrhea virus is a potential pre-evaluation indicator of immunization effects in sows during parturition under field conditions.

BACKGROUND: Porcine Epidemic Diarrhea (PED) is a highly contagious disease caused by Porcine Epidemic Diarrhea Virus (PEDV), resulting in a mortality rate of suckling piglets as high as 100%. Vaccination is the primary strategy for controlling PEDV infection, however, there is currently a lack of reliable methods for assessing the efficacy of vaccination. This study aimed to analyze serum and colostrum samples from 75 parturient sows with a specific vaccination strategy to measure levels of IgG, IgA, and neutralizing antibodies (nAbs) against PEDV, and to investigate the correlation between serum and colostrum antibody levels, as well as to identify potential biomarkers that can be used to evaluate immunization effects under field conditions. RESULTS: The findings of correlation analysis between antibody levels of IgA, IgG, and nAbs in serum or colostrum samples revealed that IgG demonstrated the most robust correlation with nAbs exhibiting a correlation coefficient of 0.64 in serum samples. Conversely, IgA exhibited the highest correlation with nAbs, with a correlation coefficient of 0.47 in colostrum samples. Additionally, the correlation analysis of antibody levels between serum and colostrum samples indicated that serum IgA displayed the strongest correlation with colostrum IgA, with a coefficient of 0.63, indicating that serum IgA may serve as a viable alternative indicator for evaluating IgA levels in colostrum samples. To further evaluate the suitability of serum IgA as a substitute marker for colostrum IgA, levels of IgA antibodies in serum samples from sows were examined both pre- and post-parturition. The findings indicated that serum IgA levels were initially low prior to the initial immunization, experienced a notable rise 21 days after immunization, and maintained a significant elevation compared to pre-immunization levels from 21 days pre-parturition to 14 days postpartum, spanning a total of 35 days. CONCLUSIONS: Serum anti-PEDV IgA antibody levels may serve as a valuable predictor for immunization effects, allowing for the assessment of colostrum IgA antibody levels up to 21 days in advance. This insight could enable veterinarians to timely adjust or optimize immunization strategies prior to parturition, thereby ensuring adequate passive immunity is conferred to piglets through colostral transfer postpartum.

Interpretable Machine Learning Model Based on Superb Microvascular Imaging for Non-Invasive Determination of Crescent Status of IgAN.

Purpose: To assess the crescentic status of IgA nephropathy (IgAN) non-invasively using a superb microvascular imaging (SMI)-based radiomics machine learning (ML) model. Patients and Methods: IgAN patients who underwent renal biopsy from June 2022 to October 2023, with two-dimensional ultrasound (US) and SMI examinations conducted one day prior to the renal biopsy. The patients selected were divided randomly into a training group and a test group in a 7:3 ratio. Radiomic features were extracted from US and SMI images, then radiomic features were constructed and ML models were further established using logistic regression (LR) and extreme gradient boosting (XGBoost)XGBoost to determine the crescentic status. The utility of the proposed model was evaluated using receiver operating characteristics, calibration, and decision curve analysis. The SHapley Additive exPlanations (SHAP) was utilized to explain the best-performing ML model. Results: A total of 147 IgAN patients were included in the study, with 103 in the training group and 44 in the test group .Among them, the US-SMI based XGBoost model achieved the best results, with an the area under the curve (AUC) of 0.839 (95% CI,0.756-0.910) and an accuracy of 78.6% in the training group.In the test group, the AUC was 0.859 (95% CI,0.721-0.964), and the accuracy was 81.8%, significantly surpassing the ML model of a single modality and the clinical model established based on occult blood. Additionally, the decision curve analysis (DCA) demonstrated that the XGBoost model provided a higher overall net benefit in the both groups. Conclusion: The SMI radiomics ML model has the capability to accurately predict the crescentic status of IgAN patients, providing effective assistance for clinical treatment decisions.

COVID-19 mRNA vaccines induce robust levels of IgG but limited amounts of IgA within the oronasopharynx of young children.

BACKGROUND: Understanding antibody responses to SARS-CoV-2 vaccination is crucial for refining COVID-19 immunization strategies. Generation of mucosal immune responses, including mucosal IgA, could be of potential benefit to vaccine efficacy, yet limited evidence exists regarding the production of mucosal antibodies following the administration of current mRNA vaccines to young children. METHODS: We measured the levels of antibodies against SARS-CoV-2 from a cohort of children under 5 years of age (N=24) undergoing SARS-CoV-2 mRNA vaccination (serially collected, matched serum and saliva samples) or in a convenience sample of children under 5 years of age presenting to pediatric emergency department (nasal swabs, N=103). Further, we assessed salivary and nasal samples for the ability to induce SARS-CoV-2 spike-mediated neutrophil extracellular traps (NET) formation. RESULTS: Longitudinal analysis of post-vaccine responses in saliva revealed the induction of SARS-CoV-2 specific IgG but not IgA. Similarly, SARS-CoV-2 specific IgA was only observed in nasal samples obtained from previously infected children with or without vaccination, but not in vaccinated children without a history of infection. In addition, oronasopharyngeal samples obtained from children with prior infection were able to trigger enhanced spike-mediated NET formation, and IgA played a key role in driving this process. CONCLUSIONS: Despite the induction of specific IgG in the oronasal mucosa, current intramuscular vaccines have limited ability to generate mucosal IgA in young children. These results confirm the independence of mucosal IgA responses from systemic humoral responses following mRNA vaccination and suggest potential future vaccination strategies for enhancing mucosal protection in this young age group.

The risk factor for adverse pregnancy outcomes and its impact on clinical effect in IgA nephropathy: A retrospective observational study.

AIM: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Pregnant IgAN patients are more susceptible to adverse pregnancy outcomes (APO). However, the risk factor for APO and its effects on the long-term renal outcome of pregnant IgAN patients remained unclear. METHODS: We performed a retrospective observational study covering 2003-2019 that included 44 female IgAN patients with pregnancy history to investigate the risk factor for APO and its impact on clinical outcome in IgAN. Renal function outcome and proteinuria remission were evaluated in pregnant IgAN women with and without APO. RESULTS: In this retrospective and observational study, we found that patients with APO exhibited higher levels of serum creatinine and IgM, and lower haemoglobin levels while other clinical characteristics, pathological characteristics and therapy protocol had no significant difference. We found that anaemia and a higher level of serum IgM were independent risk factors for APO. IgAN pregnant women without APO experienced a higher proportion of proteinuria remission than those with APO, but there is no difference in the renal function outcome. CONCLUSION: Pregnant IgAN patients with higher risks, including lower haemoglobin levels and higher IgM levels deserve intensive monitoring, and aggressive therapy to reduce proteinuria should be carried out in pregnant IgAN patients with APO.

Blood soluble CD89-IgA complex may be a potential biomarker for predicting multi-organ involvement, especially renal involvement in children with immunoglobulin A vasculitis.

BACKGROUND: Immunoglobulin A vasculitis (IgAV) is a kind of systemic vasculitis mediated by IgA immune complexes (IgA-ICs). Soluble CD89-IgA complex (sCD89-IgA) as a type of IgA-IC associated with renal involvement in IgAV, the ability of blood sCD89-IgA as a biomarker to predict renal or multi-organ involvement in children with IgAV is not evident, and this study mainly focused on this. METHODS: The clinical characteristics and blood samples of 57 pediatric patients with IgAV were collected. ELISA was used to detect plasma IgA-ICs and sCD89-IgA levels. Serum IgA levels were detected by Nephelometry method. Statistical analysis was conducted to analyze the relationship between sex, age, serum IgA levels, plasma IgA-ICs levels, plasma sCD89-IgA levels and the involvement of multiple organs (except skin) including kidneys in these patients. RESULTS: Compared to patients with simple skin involvement, patients with multi-organ involvement, especially kidneys, had higher levels of plasma IgA-ICs and sCD89-IgA, and the statistical difference was significant. In addition, a high level of plasma sCD89-IgA was a high-risk factor for patients to develop multi-organ or renal involvement in addition to the skin. ROC curve analysis showed that the AUC was 0.861 (Sensitivity: 83 %, Specificity: 88 %, p < 0.0001) when plasma sCD89-IgA predicted multi-organ involvement, and AUC 0.926 (Sensitivity: 94 %, Specificity: 88 %, p < 0.0001) for predicting renal involvement. CONCLUSIONS: The results suggested that plasma sCD89-IgA may be a potential biomarker for predicting multi-organ involvement (in addition to skin), especially renal involvement in IgAV pediatric patients.

SARS-CoV-2 as a trigger of IgA vasculitis: a clinical case and literature review.

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, has negatively affected global health. COVID-19 has been associated with a variety of autoimmune and inflammatory disorders, complicating its respiratory manifestations. SARS-CoV-2 triggers inflammatory reactions which may involve multiple organs and systems. The proof for IgA involvement in the immune reactions to coronavirus infection is growing, particularly in the case of IgA immune complex deposition diseases such as IgA vasculitis (IgAV) and IgA nephropathy.This report presents a case of IgAV caused by SARS-CoV-2 in a 53-year-old man. His symptoms included papillomatous, bright red rashes, urticaria throughout the body, aphthous stomatitis, pain in all joints and muscles, weakness, malaise, abdominal pain, face swelling, and arterial hypertension (160/100 mmHg). He received intravenous methylprednisolone (250 mg) and then oral methylprednisolone (16 mg) treatment, which improved his condition. This improvement included the disappearance of abdominal and joint pain and skin rashes.This article also provides an overview of published cases of IgAV after SARS-CoV-2. It may alert rheumatologists and allied specialists of clinical features of IgAV and guide them how to diagnose and treat this disease.

Denovo glomerulonephritis associated with IgA anti-GBM alloantibodies after kidney transplantation in Alport syndrome: A case report with diagnostic implications.

Alport syndrome (AS) is a hereditary disorder caused by pathogenic variants in COL4A3, COL4A4, or COL4A5 genes expressing α3, α4, and α5 chains of basement membrane type IV collagen (COL4). The triple-helical α3α4α5(IV) protomer is a major component of the mature glomerular basement membrane (GBM) whose defective formation in AS leads to structural GBM disruption and kidney dysfunction, often resulting in kidney replacement therapy. A genetically intact renal graft exposes the immune system to a non-tolerized α3α4α5(IV) component and an alloimmune response eventually ensues. So far, only IgG alloantibodies reacting against COL4 have been reported in AS alloimmune responses. Here, we report alloimmune glomerulonephritis mediated by IgA antibodies against the non-collagenous C-terminal domain 1 of the α5(IV) chain in a patient with autosomal recessive AS following a second kidney transplantation. The patient presented a not previously described biallelic variant in the COL4A4 gene. Immunological, diagnostic, and clinical implications are discussed.

Understanding antibody magnitude and durability following vaccination against SARS-CoV-2.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in transient antibody response against the spike protein. The individual immune status at the time of vaccination influences the response. Using mathematical models of antibody decay, we determined the dynamics of serum immunoglobulin G (IgG) and serum immunoglobulin A (IgA) over time. Data fitting to longitudinal IgG and IgA titers was used to quantify differences in antibody magnitude and antibody duration among infection-naïve and infection-positive vaccinees. We found that prior infections result in more durable serum IgG and serum IgA responses, with prior symptomatic infections resulting in the most durable serum IgG response and prior asymptomatic infections resulting in the most durable serum IgA response. These findings can guide vaccine boosting schedules.

The serological diagnostic value of EBV-related IgA antibody panels for nasopharyngeal carcinoma: a diagnostic test accuracy meta-analysis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is diagnosed relatively late and has a poor prognosis, requiring early detection to reduce the disease burden. This diagnostic test accuracy meta-analysis evaluated the serological diagnostic value of nine EBV-related IgA antibody panels (EBNA1-IgA, VCA-IgA, EA-IgA, Zta-IgA, EBNA1-IgA + VCA-IgA, VCA-IgA + EA-IgA, VCA-IgA + Rta-IgG, EBNA1-IgA + VCA-IgA + Zta-IgA and VCA-IgA + EA-IgA + Rta-IgG), aiming to identify suitable serological detection biomarkers for NPC screening. METHODS: PubMed, Embase, China National Knowledge Infrastructure and Chinese BioMedical Literature Database were searched from January 1st, 2000 to September 30th, 2023, with keywords nasopharyngeal carcinoma, IgA, screening, early detection, early diagnosis, sensitivity and specificity. Articles on the diagnostic value of serum EBV-related IgA antibody panels for NPC were included. Study selection, data extraction, and quality assessment were performed independently by two researchers, and a third researcher was consulted in the case of disagreement. Bivariate models were used for statistical analysis. The quality of included studies was evaluated through Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). RESULTS: A total of 70 articles were included, involving 11 863 NPC cases and 34 995 controls. Among the nine EBV-related IgA antibody panels, EBNA1-IgA + VCA-IgA [0.928 (0.898, 0.950)], VCA-IgA + Rta-IgG [0.925 (0.890, 0.949)], EBNA1-IgA + VCA-IgA + Zta-IgA [0.962 (0.909, 0.985)] and VCA-IgA + EA-IgA + Rta-IgG [0.945 (0.918, 0.964)] demonstrated higher pooled sensitivity (95%CI). In terms of diagnostic odds ratio (DOR) (95%CI), EBNA1-IgA + VCA-IgA [107.647 (61.173, 189.430)], VCA-IgA + Rta-IgG [105.988 (60.118, 186.857)] and EBNA1-IgA + VCA-IgA + Zta-IgA [344.450 (136.351, 870.153)] showed superior performance. Additionally, the SROC curves for EBNA1-IgA + VCA-IgA and VCA-IgA + Rta-IgG were more favorable. However, publication bias was detected for VCA-IgA (P = 0.005) and EBNA1-IgA + VCA-IgA (P = 0.042). CONCLUSIONS: In general, parallel detection of serum EBNA1-IgA, VCA-IgA and Zta-IgA antibodies using ELISA demonstrates better pooled sensitivity and DOR among the studied panels. In the cases where fewer indicators are used, serum VCA-IgA and EBNA1-IgA/Rta-IgG antibody panel exhibits a comparable performance. TRIAL REGISTRATION: The International Prospective Register of Systematic Reviews registration number: CRD42023426984, registered on May 28, 2023.

Clinical characteristics and outcomes of Brazilian patients with duodenal-type follicular lymphoma: a multicenter retrospective study.

Duodenal-type follicular lymphoma (DFL) is a rare subtype classified by the 5th edition of the WHO and international consensus classifications of lymphoid neoplasms, typically presenting as localized disease with favorable outcomes. This multicenter retrospective study examines 53 Brazilian DFL patients with a median age of 58.2 years (33-85), with males comprising 50% (n = 27). According to Lugano GI tract classification, 40 patients (75%) were stage I. Median follow-up was 2.9 years (range 0.1-11). Incidental diagnosis occurred in 28 patients (52.8%) during routine endoscopy; 24 patients (45%) presented mild gastrointestinal symptoms. Treatments included watchful waiting (32 patients, 60.4%), rituximab monotherapy (15 patients, 28.3%), radiotherapy (three patients, 5.7%), and chemoimmunotherapy (three patients, 5.7%). Three patients experienced disease progression; watchful waiting showed three spontaneous remissions. No deaths occurred during follow-up. This study, the first from Latin America, demonstrates a good prognosis across treatments, highlighting Watchful waiting's effectiveness.

Exploring the crosstalk molecular mechanisms between IgA nephropathy and Sjögren's syndrome based on comprehensive bioinformatics and immunohistochemical analyses.

IgA nephropathy (IgAN) and Sjogren's syndrome (SS) are two autoimmune diseases with undetermined etiology and related to abnormal activation of lymphocytes. This study aims to explore the crucial genes, pathways and immune cells between IgAN and SS. Gene expression profiles of IgAN and SS were obtained from the Gene Expression Omnibus and Nephroseq data. Differentially expressed gene (DEG) and weighted gene co-expression network analyses (WGCNA) were done to identify common genes. Enrichment analysis and protein-protein interaction network were used to explore potential molecular pathways and crosstalk genes between IgAN and SS. The results were further verified by external validation and immunohistochemistry (IHC) analysis. Additionally, immune cell analysis and transcription factor prediction were also conducted. The DEG analysis revealed 28 commonly up-regulated genes, while WGCNA identified 98 interactively positive-correlated module genes between IgAN and SS. The enrichment analysis suggested that these genes were mainly involved in the biological processes of response to virus and antigen processing and presentation. The external validation and IHC analysis identified 5 hub genes (PSMB8, PSMB9, IFI44, ISG15, and CD53). In the immune cell analysis, the effector memory CD8 T and T follicular helper cells were significantly activated, and the corresponding proportions showed positively correlations with the expressions of the 5 hub genes in the two autoimmune diseases. Together, our data identified the crosstalk genes, molecular pathways, and immune cells underlying the IgAN and SS, which provides valuable insights into the intricate mechanisms of these diseases and offers potential intervention targets.

Requirement of a Wnt5A-microbiota axis in the maintenance of gut B-cell repertoire and protection from infection.

We investigated the influence of a Wnt5A-gut microbiota axis on gut B-cell repertoire and protection from infection, having previously demonstrated that Wnt5A in association with gut commensals helps shape gut T-cell repertoire. Accordingly, Wnt5A heterozygous mice, which express less than wild-type level of Wnt5A, and their isolated Peyer's patches (PPs) were studied in comparison with the wild-type counterparts. The percentages of IgM- and IgA-expressing B cells were quite similar in the PP of both sets of mice. However, the PP of the Wnt5A heterozygous mice harbored significantly higher than wild-type levels of microbiota-bound B cell-secreted IgA, indicating the prevalence of a microbial population therein, which is significantly altered from that of wild-type. Additionally, the percentage of PP IgG1-expressing B cells was appreciably depressed in the Wnt5A heterozygous mice in comparison to wild-type. Wnt5A heterozygous mice, furthermore, exhibited notably higher than the wild-type levels of morbidity and mortality following infection with Salmonella typhimurium, a common gut pathogen. Differences in morbidity/mortality correlated with considerable disparity between the PP-B-cell repertoires of the Salmonella-infected Wnt5A heterozygous and wild-type mice, in which the percentage of IgG1-expressing B1b cells in the PP of heterozygous mice remains significantly low as compared to wild-type. Overall, these results suggest that a gut Wnt5A-microbiota axis is intrinsically associated with the maintenance of gut B-cell repertoire and protection from infection.IMPORTANCEAlthough it is well accepted that B cells and microbiota are required for protection from infection and preservation of gut health, a lot remains unknown about how the optimum B-cell repertoire and microbiota are maintained in the gut. The importance of this study lies in the fact that it unveils a potential role of a growth factor termed Wnt5A in the safeguarding of the gut B-cell population and microbiota, thereby protecting the gut from the deleterious effect of infections by common pathogens. Documentation of the involvement of a Wnt5A-microbiota axis in the shaping of a protective gut B-cell repertoire, furthermore, opens up new avenues of investigations for understanding gut disorders related to microbial dysbiosis and B-cell homeostasis that, till date, are considered incurable.

A case of atypical IgA paraprotein interference on multiple chemistry assays: How to deal with it.

This case report discusses how paraproteins interfere with multiple chemistry analyses and protocols to overcome such obstacles. A serum specimen containing two monoclonal IgA (llight chain) paraproteins is subjected to a battery of tests on three wet chemistry platforms - AU5800, Cobas Pure, and Alinityci; the results were compared with those on a Vitros 350/ ECiQ dry chemistry platform. Paraprotein interference was found to affect the bilirubins, inorganic phosphate, and iron, whose repeat runs were also found to be irreproducible. Dilution with normal saline also failed to produce a satisfactory effect. Deproteinization by polyethylene glycol and dilution of the specimen with a normal serum specimen were observed to produce desirable results. Interference by IgA paraprotein on measurement of the bilirubin, phosphate, and iron in the wet chemistry system can be mitigated either by deproteinization or by dilution with normal serum.

Clinical significance of glomerular IgM deposit in IgA nephropathy: a 5-year follow-up study.

The significance of glomerular IgM deposit intensity in IgA Nephropathy (IgAN) remained ambiguous and requires further research. Patients with biopsy-proven IgAN in our hospital from January 2018 to May 2023 were recruited into this retrospective single-center study. Patients who presented with positive IgM deposit were included in IgM + cohort while patients with negative IgM deposit were included in IgM- cohort. Of the IgM+, patients whose IF intensity of IgM deposits exceeded 1+ formed IgM-H cohort while patients whose IF intensity of IgM deposits was equal to 1+ consisted IgM-L cohort. Pairwise comparisons were performed among these cohorts to determine clinical disparities, following the propensity score matching process. Among 982 IgAN patients, 539 patients presented with positive IgM deposit. The Kaplan-Meier analysis showed that the IgM deposit did not contribute adversely to the outcomes (eGFR decreased from the baseline ≥ 50% continuously or reached end-stage renal disease). However, the Cox regression analysis showed that increased intensity of IgM deposit was an independent risk factor (p = 0.03) in IgM+. The IgM-H exhibited more pronounced segmental glomerulosclerosis (p = 0.02) than the IgM-L, which may also be associated more directly with higher urine protein levels (p = 0.02). Moreover, our generalized linear mixed model demonstrated a remarkably higher urine albumin/creatinine ratio (p < 0.01) and serum creatinine (p = 0.04) levels as well as lower serum albumin (p < 0.01) level in IgM-H persistently during the 5-year follow-up. This study concluded that increased intensity of glomerular IgM deposits may contribute adversely to clinicopathologic presentation and outcome in those IgM + patients.

Clinical features and prognosis of patients with anti-GBM disease combined with mesangial IgA deposition.

Introduction: Anti-GBM diseases with IgA deposition in the mesangial region are rarely described.The factors influencing renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition are unknown. Methods: We searched the pathological reports of the First Affiliated Hospital of Zhengzhou University from 2015 to 2023 and found that a total of 72 patients with the anti-GBM disease and 25 patients combined with mesangial IgA deposition. We studied the clinical and pathological features, renal prognosis, and the factors affecting renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition. Results: Their median age was 44 years, and their age distribution was unimodal. The proportion of oliguria or anuria in patients with anti-GBM disease combined with mesangial IgA deposition was significantly lower than that in patients with classic anti-GBM disease (13.04 vs. 42.31%, p=0.030). Their 24-hour urinary protein excretion was significantly higher [median:3.25 vs. 1.12g/24h, Interquartile range(IQR):1.032~3.945 vs. 0.63~1.79g/24h, p=0.020], serum creatinine (SCr) level at the initial diagnosis was lower(median:456.0 vs. 825.5µmol/L, IQR:270.0~702.0 vs. 515.8~1231.2µmol/L, p=0.002), peak SCr level was lower (median: 601.0 vs. 907.2µmol/L, IQR: 376.5~937.0 vs. 607.0~1361.2µmol/L, p=0.007), and their serum complement 3(C3) level was higher(median: 1.275 vs. 1.015g/L, IQR:1.097~1.462 vs. 0.850~1.220g/L, p=0.027). They had better renal outcomes during follow-up (p<0.001). After adjustment for hypertension, oliguria or anuria, and crescents%, IgA deposition in the mesangial region was still an independent protective factor (p=0.003) for ESRD in anti-GBM patients. Hypertension (p=0.026) and SCr levels at initial diagnosis (p=0.004) were risk factors for renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition. Discussion: Patients with anti-GBM disease combined with mesangial IgA deposition have less severe renal impairment and better renal prognosis than patients with classic anti-GBM disease.

Recurrent, atraumatic acute compartment syndrome secondary to IgA vasculitis: A case report.

Acute compartment syndrome is a surgical emergency requiring rapid recognition in the emergency department to minimize morbidity and mortality. It is most commonly caused by traumatic extremity fractures, which account for about 75% of cases. Atraumatic acute compartment syndrome is substantially less common with current evidence mostly limited to case reports, and diagnosis is made more challenging by the absence of an obvious traumatic injury. We present the case of a young adult female patient with IgA vasculitis who developed recurrent, atraumatic acute compartment syndrome and was successfully managed with prompt fasciotomy. This is the first case of spontaneous intramuscular hemorrhage, a rare sequela of IgA vasculitis, leading to recurrent, atraumatic acute compartment syndrome. This case highlights the importance of both a thorough physical exam and maintaining a high suspicion for acute compartment syndrome in the absence of injury to ensure patients receive prompt surgical evaluation for definitive care.