Anti-CD8 Monoclonal Antibody Protects against Spontaneous IgA Nephropathy in ddY Mice

Shimamine, Ryosuke; Shibata, Ryuichiro; Ozono, Yoshiyuki; Harada, Takashi; Taguchi, Takashi; Hara, Kohei; Kono, Shigeru

doi:10.1159/000044941

Cited by 10 publications

(3 citation statements)

References 21 publications

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“…In addition, Tomino et al uncovered that CD8 + T cells were the most abundant glomerular-infiltrating cell in IgAN patients [ 74 ]. Anti-CD8 T cell treatment has been proved to trigger a profitable effect of suppressing mesangial expansion in an animal model of IgAN [ 75 ]. Another study showed that, compared to children with non-progressive IgAN, significantly higher percentages of CD8 + T cells in the glomeruli and in the interstitium were detected in the children with progressive IgAN [ 76 ].…”

Section: Discussionmentioning

confidence: 99%

Identifying potential biomarkers for the diagnosis and treatment of IgA nephropathy based on bioinformatics analysis

Liu

et al. 2023

BMC Med Genomics

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Background IgA nephropathy (IgAN) has become the leading cause of end-stage renal disease in young adults. Nevertheless, the current diagnosis exclusively relies on invasive renal biopsy, and specific treatment is deficient. Thus, our study aims to identify potential crucial genes, thereby providing novel biomarkers for the diagnosis and therapy of IgAN. Methods Three microarray datasets were downloaded from GEO official website. Differentially expressed genes (DEGs) were identified by limma package. GO and KEGG analysis were conducted. Tissue/organ-specific DEGs were distinguished via BioGPS. GSEA was utilized to elucidate the predominant enrichment pathways. The PPI network of DEGs was established, and hub genes were mined through Cytoscape. The CTD database was employed to determine the association between hub genes and IgAN. Infiltrating immune cells and their relationship to hub genes were evaluated based on CIBERSORT. Furthermore, the diagnostic effectiveness of hub markers was subsequently predicted using the ROC curves. The CMap database was applied to investigate potential therapeutic drugs. The expression level and diagnostic accuracy of TYROBP was validated in the cell model of IgAN and different renal pathologies. Results A total of 113 DEGs were screened, which were mostly enriched in peptidase regulator activity, regulation of cytokine production, and collagen-containing extracellular matrix. Among these DEGs, 67 genes manifested pronounced tissue and organ specificity. GSEA analysis revealed that the most significant enriched gene sets were involved in proteasome pathway. Ten hub genes (KNG1, FN1, ALB, PLG, IGF1, EGF, HRG, TYROBP, CSF1R, and ITGB2) were recognized. CTD showed a close connection between ALB, IGF, FN1 and IgAN. Immune infiltration analysis elucidated that IGF1, EGF, HRG, FN1, ITGB2, and TYROBP were closely associated with infiltrating immune cells. ROC curves reflected that all hub genes, especially TYROBP, exhibited a good diagnostic value for IgAN. Verteporfin, moxonidine, and procaine were the most significant three therapeutic drugs. Further exploration proved that TYROBP was not only highly expressed in IgAN, but exhibited high specificity for the diagnosis of IgAN. Conclusions This study may offer novel insights into the mechanisms involved in IgAN occurrence and progression and the selection of diagnostic markers and therapeutic targets for IgAN.

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Section: Discussionmentioning

confidence: 99%

Identifying potential biomarkers for the diagnosis and treatment of IgA nephropathy based on bioinformatics analysis

Liu

et al. 2023

BMC Med Genomics

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“…However, some experimental studies have indicated that CD8 + cells and the soluble factor secreted by them might directly and/or indirectly promote tissue damage [16]. Recently, Shimamine et al [17] reported that anti-CD8 T-lymphocyte treatment produced a protective effect against mesangial injury in ddY mice, an animal model of spontaneous IgAN.…”

Section: Discussionmentioning

confidence: 99%

Glomerular CD8 + cells predict progression of childhood IgA nephropathy

Watanabe¹,

Kawachi²,

Ikezumi³

et al. 2001

Pediatric Nephrology

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The aim of this study was to evaluate whether the infiltrating T-lymphocyte can be a predictor in the disease progression of IgA nephropathy (IgAN). Twenty children with IgAN, followed for more than 5 years, were divided into progressive (n=5) and non-progressive groups (n=15). We assessed glomerular and interstitial infiltration of T-lymphocytes (CD4+ and CD8+ cells) and expression of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta (TGF-beta) using an indirect immunofluorescence method on the renal biopsies. We analyzed their relationship to the degree of proteinuria, histological changes, and prognosis. The number of CD8+ cells in glomeruli and in interstitium was higher in the progressive group than in the non-progressive group. The glomerular alpha-SMA staining was more intensive in the progressive group than in the non-progressive group. Urinary protein and the degree of histological changes were also higher in the progressive group than in the non-progressive group. Among these markers, the number of glomerular CD8+ cells was the most apparent difference between the two groups. In conclusion, these results indicate that the number of glomerular CD8+ cells is the most sensitive predictor of disease progression in childhood IgAN.

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“…Sabadini et al (88) reported that the degree of interstitial CD8 + lymphocyte infiltration was correlated with the severity of interstitial fibrosis and renal impairment. Shimamine et al (89) reported that anti-CD8 T-lymphocyte treatment produced a protective effect against mesangial injury in ddY mice, an animal model of spontaneous IgAN. In another study, 20 children with IgAN who were followed for >5 years were divided into the progressive (n=5) and non-progressive groups (n=15).…”

Section: Cd8 + Cellsmentioning

confidence: 99%

T lymphocytes in IgA nephropathy (Review)

Tang

et al. 2020

Exp Ther Med

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Immunoglobulin A nephropathy (IgAN), the most common primary glomerulonephritis worldwide, is the main cause of end-stage renal disease. IgAN is characterized by the accumulation of immune complexes in the circulation, which contain abnormal levels of IgA. IgAN primarily results from galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1 deposition in the renal mesangium, causing local proliferation and matrix expansion. Gd-IgA1 has been confirmed as one of the key effectors in the pathogenesis of IgAN, but the origin of Gd-IgA1 is not clear. Recent studies have shown that Gd-IgA1 deposition could be the result of mucosally primed plasma cells and is associated with T cell dysregulation. T cells contribute to the IgA response and play an important role in the development of IgAN. In the present review, the latest discoveries regarding the role of T lymphocytes in the pathogenesis of IgAN have been summarized. Understanding these advances will allow novel therapeutic strategies for the treatment of IgAN.

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Anti-CD8 Monoclonal Antibody Protects against Spontaneous IgA Nephropathy in ddY Mice

Cited by 10 publications

References 21 publications

Identifying potential biomarkers for the diagnosis and treatment of IgA nephropathy based on bioinformatics analysis

Identifying potential biomarkers for the diagnosis and treatment of IgA nephropathy based on bioinformatics analysis

Glomerular CD8 + cells predict progression of childhood IgA nephropathy

T lymphocytes in IgA nephropathy (Review)

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