The mucosal immune system and IgA nephropathy

Gesualdo, Loreto; Leo, Vincenzo Di; Coppo, Rosanna

doi:10.1007/s00281-021-00871-y

Cited by 74 publications

(49 citation statements)

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“…Yuan et alfound that the gene of CXCL2 was crucially associated with the immune infiltration between CD and IgA nephropathy [ 29 ]. Alteration of the microbiota could lead to ecological dysregulation, which regulated immune-mediated IBD and IgA nephropathy [ 30 , 31 ]. In a study, a reduction in circulating IgA complexes and proteinuria was observed in patients with IgA nephropathy on a gluten-free diet for 6 months to 4 years [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

The pathological and outcome characteristics of renal lesions in Crohn’s disease

Zhang

Dong

et al. 2022

BMC Nephrol

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Background The inflammatory bowel disease, containing Crohn’s disease and ulcerative colitis, was rare in the population, especially in the complication of kidney disease. A few studies had found proteinuria played a potential indicator of inflammatory bowel disease occurrence and activity. This study aimed to better define the histopathologic spectrum and study the outcome of renal disease in Crohn’s disease. Methods A retrospective study of 3557 Crohn's disease from January 1st, 2016 to July 1st, 2021 in the Sixth Affiliated Hospital of Sun Yat-sen University identified 20 (0.56% [20/3557]) patients who underwent kidney biopsy. All biopsy specimens were examined by standard procedures containing light microscopy, immunofluorescence, and electron microscopy. Results Twenty cases were shown in this review study. Subnephrotic proteinuria (30% [6 of 20]), persistent hematuria and proteinuria (25% [5 of 20]), and isolated hematuria with acanthocytes (25% [5 of 20]) were the main indications for kidney biopsy. The most common diagnosis was IgA nephropathy (70% [14/20]), followed by minimal change disease (10% [2/20]), acute interstitial nephritis (5% [1/20]), granulomatous interstitial nephritis (5% [1/20]), non-IgA mesangial proliferative nephritis (5% [1/20]) and thin basement membrane nephropathy (5% [1/20]). The Lee classification of IgA nephropathy was mostly II or III level. Glomerular mesangial hyperplasia was the most common pathologic manifestation according to the MEST-C Sore. After twelve-month treatment, the majority of patients turned to complete remission of renal disease by measuring proteinuria, while 3 patients still stayed in the relapse stage and 6 patients turned to partial remission by measuring hematuria. Conclusions IgA nephropathy is the most common kidney biopsy diagnosis in Crohn's disease. Renal damage in Crohn's disease mainly involves the glomerulus, especially the mesangial matrix. After the treatment, proteinuria might be in remission, but hematuria remains.

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Section: Discussionmentioning

confidence: 99%

The pathological and outcome characteristics of renal lesions in Crohn’s disease

Zhang

Dong

et al. 2022

BMC Nephrol

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“… 50 Therefore, aberrant mucosal immune response is considered to be involved in the pathogenesis of IgAN. 51 …”

Section: Discussionmentioning

confidence: 99%

“…Some of these cytokines can then cause podocyte injury and induce proteinuria. The figure refers to the pathogenesis of IgAN by Gesualdo et al 51 …”

Section: Discussionmentioning

confidence: 99%

New-onset IgA nephropathy following COVID-19 vaccination

2022

QJM: An International Journal of Medicine

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Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused significant economic and health damage worldwide. Rapid vaccination is one of the key strategies to curb severe illness and death due to SARS-CoV-2 infection. Hundreds of millions of people worldwide have received various COVID-19 vaccines, including mRNA vaccines, inactivated vaccines, and adenovirus-vectored vaccines, but the side effects and efficacy of most vaccines have not been extensively studied. Recently, there have been increasing reports of immunoglobulin A nephropathy (IgAN) after COVID-19 vaccination, however, whether their relationship is causal or coincidental remains to be verified. Here, we summarize the latest clinical evidence of IgAN diagnosed by renal biopsy associated with the COVID-19 vaccine published by July 10, 2022 with the largest sample size, and propose a hypothesis for the pathogenesis between them. At the same time, the new opportunity presented by COVID-19 vaccine allows us to explore the mechanism of IgAN recurrence for the first time. Indeed, we recognize that large-scale COVID-19 vaccination has enormous benefits in preventing COVID-19 morbidity and mortality. The purpose of this review is to help guide the clinical assessment and management of IgA nephropathy post COVID-19 vaccination and to enrich the “multi-hit” theory of IgA nephropathy.

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“…As mentioned above, the “first hit” is that individuals with a genetic susceptibility develop abnormal immune responses to common and environmental antigens, which leads to an increase of galactose-deficient IgA1 in circulation. A growing body of evidence suggests that abnormality of intestinal mucosal immunity plays an important role in IgAN [ 25 ]. Integrin alpha M (ITGAM) encodes the integrin alpha M chain (CD11b) and belongs to the integrin family.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of glomerulotubular crosstalk genes mediating IgA nephropathy by integrated bioinformatics

Bai

2022

BMC Nephrol

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Background IgA nephropathy (IgAN), which has been reported as the most prevalent glomerulonephritis globally, is the major contributor to end-stage renal diseases. This bioinformatics study aimed to explore glomerulotubular crosstalk genes and dysregulated pathways relating to the pathogenesis of IgAN. Methods The microarray datasets from the Gene Expression Omnibus (GEO) database were searched. Weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) of both glomeruli and tubulointerstitium were conducted individually. The co-expression gene modules of glomeruli and tubulointerstitium were compared via gene function enrichment analysis. Subsequently, the crosstalk co-expression network was constructed via the STRING database and key genes were mined from the crosstalk network. Finally, key genes were validated using another GEO dataset (GSE99340) containing RNA-seq data of IgAN and lupus nephritis, and their potential diagnostic values were shown using receiver operating characteristic (ROC) analysis. Results Five hundred eighty-three DEGs and eight modules were identified in glomerular samples, while 272 DEGs and four modules were in tubulointerstitial samples. There were 119 overlapping DEGs between the two groups. Among the distinctive modules, four modules in glomeruli and one module in tubulointerstitium were positively associated with IgAN. While four modules in glomeruli and two modules in tubulointerstitium were negatively associated with IgAN. The top ten key genes screened by CytoHubba were ITGAM, ALB, TYROBP, ITGB2, CYBB, HCK, CSF1R, LAPTM5, FN1, and CTSS. Compared with lupus nephritis, there were significant differences in the expression levels of CYBB, CTSS and TYROBP (P < 0.05), while other key genes showed no significant difference. Meanwhile, CYBB, CTSS, and TYROBP demonstrated possible diagnostic significance. Conclusions The crosstalk genes confirmed in this study may provide novel insight into the pathogenesis of IgAN. Immune-related pathways are associated with both glomerular and tubulointerstitial injuries in IgAN. The glomerulotubular crosstalk might perform a role in the pathogenesis of IgAN.

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The mucosal immune system and IgA nephropathy

Cited by 74 publications

References 100 publications

The pathological and outcome characteristics of renal lesions in Crohn’s disease

The pathological and outcome characteristics of renal lesions in Crohn’s disease

New-onset IgA nephropathy following COVID-19 vaccination

Identification and validation of glomerulotubular crosstalk genes mediating IgA nephropathy by integrated bioinformatics

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