Immunological abnormalities in patient with IgA nephropathy

Ihm, Chun-Gyoo; Woo, Jeong Taek; Chang, Young‐Wook; Kwon, Oh‐Jun; Kim, M. J.

doi:10.3346/jkms.1986.1.1.43

Cited by 3 publications

(4 citation statements)

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“…Although the pathogenesis of IgA nephropathy is not well defined, it is suggested that immunoregulatory dysfunciton plays a major role 1 – 5 ) . In IgA nephropathy, many evidences of immunological involvements such as the elevated level of serum IgA 30 ) and the circulating IgA immune complexes 31 – 34 ) , the deposition of IgA in dermal capillaries, liver, lung, and gut 35 , 52 ) , and the recurrence of original disease in renal allograft 36 ) were demonstrated.…”

Section: Discussionmentioning

confidence: 99%

“…Although the immunopathogenesis of IgA nephropathy is not completely defined, it is suggested that immunoregulatory dysfunction plays an important role in the pathogenesis of IgA nephropathy 1 – 5 ) . Recent studies also suggest the association between the disordered immunoregulation of T cell and the disease activity of IgA nephropathy 6 – 8 ) .…”

Section: Introductionmentioning

confidence: 99%

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Production of Interleukin-2 IL-2 and Expression of IL-2 Receptor in Patients with IgA Nephropathy

Lee

Kim

1992

Korean J Intern Med

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BackgroundIL-2 production has been measured in several disease including type I diabetes mellitus9), systemic lupus erythematosus10,11), acquired immunodeficiency syndrome12,13) and active pulmonary sarcoidosis14) and its pathogenetic role was suggested. In IgA nephropathy, altered T cell subsets were reported to be associated with increased synthesis of IgA15–19). The altered IL-2 production and the expression of IL-2 receptor might be involved in the pathogenesis of IgA nephropathy20–23).MethodsTo investigate the role of T cell mediated immunity in the pathogenesis of IgA nephropathy, the immune parameters such as T cell subsets, NK cell activity, interleukih-2 (IL-2) production and IL-2 receptor expression on peripheral blood mononuclear cells (PBMC) were measured before and/or after phytohemagglutinin (PHA) stimulation in 15 patients with IgA nephropathy. Age and sex matched 15 healthy controls and the correlations between the IL-2 production and immune parameters were evaluated.ResultsThe mean percentages of T helper/inducer cells (CD4), T suppressor/cytotoxic cells (CD8) end the CD4/CD8 ratio of the patients were not different from those of controls and the proportions of CD8 CD11b cell in the patients (21.0±3.6%) were significantly lower than those in controls (30.5±5.3%) (p<0.005). The production of IL-2 by fresh PBMC of both patients and controls was in undetectable ranges. The production of IL-2 by PHA stimulated PBMC of patients was significantly higher than that of controls (140.03±43.2 U/ml vs 106.5±42.1 U/ml, p<0.05). The proportions of lymphocytes expressing the IL-2 receptor (CD25) before the stimulation with PHA in patients were 1.22±1.00 percents and were not different from those in controls (1.12±0.78 percents). The correlations between the production of IL-2 and the concentrations of serum IgA, the degrees of histologic alterations and the proportions of CD8 and CD8CD11b cells were not significant. There was a weak tendency of a positive correlation (p<0.1) between the production of IL-2 and the proportions of CD4 cells, and the CD4/CD8 ratio showed a significant correlation with the production of IL-2 (p<0.05). After PHA stimulation, the mean percentages of lymphocytes expressing the IL-2 receptors in patients were increased to 47.6±8.9 percents which is higher than those (40.4±9.9%) in controls (p<0.05). The NK cell activity of the patients was higher than that of controls (75.6±19.6% vs 56.1±16.2%, p<0.005), and was well correlated with the production of IL-2 by PBMC (r = 0.89, p<0.05).ConclusionsIt seemed that patients with IgA nephropathy have an 'latent' cellular immunoregulatory dysfunciton that becomes apparent on the stimulation of extrinsic antigens or mitogens.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Production of Interleukin-2 IL-2 and Expression of IL-2 Receptor in Patients with IgA Nephropathy

Lee

Kim

1992

Korean J Intern Med

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“…S5B). Previous two studies have suggested that the decrease in number and function of NK cells were associated with the disease progression of IgAN [ 31 , 32 ]. Altered monocyte gene expression patterns and numbers were found to be pathogenic factors in IgAN [ 33 , 34 ].…”

Section: Resultsmentioning

confidence: 99%

Single-cell RNA-sequencing reveals distinct immune cell subsets and signaling pathways in IgA nephropathy

Zeng

Wang

et al. 2021

Cell Biosci

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Background IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally. Increasing evidence suggests the importance of host immunity in the development of IgAN, but its dynamics during the early stage of IgAN are still largely unclear. Results Here we successfully resolved the early transcriptomic changes in immune cells of IgAN by conducting single-cell RNA-sequencing (scRNA-seq) with peripheral blood mononuclear cells. The differentially expressed genes (DEGs) between control and IgAN were predominantly enriched in NK cell-mediated cytotoxicity and cell killing pathways. Interestingly, we discovered that the number and cytotoxicity of NK cells are significantly reduced in IgAN patients, where both the number and marker genes of NK cells were negatively associated with the clinical parameters, including the levels of urine protein creatinine ratio (UPCR), serum galactose-deficient IgA1 and IgA. A distinctive B cell subset, which had suppressed NFκB signaling was predominantly in IgAN and positively associated with disease progression. Moreover, the DEGs of B cells were enriched in different viral infection pathways. Classical monocytes also significantly changed in IgAN and a monocyte subset expressing interferon-induced genes was positively associated with the clinical severity of IgAN. Finally, we identified vast dynamics in intercellular communications in IgAN. Conclusions We dissected the immune landscape of IgAN at the single-cell resolution, which provides new insights in developing novel biomarkers and immunotherapy against glomerulonephritis.

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“…Yano N [ 53 ] reported that HLA-DR-positive NK cells were significantly increased in IgA nephropathy patients, and HLA-DR-positive NK cells had greater ability to produce IFN-γ than HLA-DR-negative NK cells, thus exacerbating kidney injury [ 54 ]. Previous studies have shown that the decline in the number and function of NK cells was closely related to the disease progression of IgA nephropathy [ 55 , 56 ]. Recently Zeng H [ 13 ] further confirmed through single-cell RNA-sequencing that total NK (CD56 + CD3 ±) and NK-1 and NK-2 (CD56 + CD3-) cell numbers were significantly reduced in IgA nephropathy.…”

Section: Discussionmentioning

confidence: 99%

Causal role of immune cells in IgA nephropathy: a mendelian randomization study

Shu,

Ge,

2024

Renal Failure

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Background Previous observational studies have shown that immune cells play an important role in IgA nephropathy. However, the specific causal relationship between the two is inconsistent. Methods We used a two-sample mendelian randomization(MR) analysis to investigate the causal association between 731 immune cell signatures and IgA nephropathy in this study. Based on published GWAS data, immune cells were characterized by four immune types absolute cell (AC) counts, median fluorescence intensity (MFI), morphological parameters (MP), relative cell (RC) counts. Meanwhile, heterogeneity test, horizontal pleiotropy and sensitivity test were used to evaluate the robustness and reliability of the results. Results An important causal association was achieved for 14 RC traits/IgA nephropathy, 3 AC traits/IgA nephropathy, 10 MFI traits/IgA nephropathy, and 1 MP trait/IgA nephropathy. However, after false discovery rate (FDR) correction, only one immunophenotype was found to be protective against IgA nephropathy. The OR of herpesvirus entry mediator (HVEM) on terminally differentiated CD4+ T cell (maturation stages of T-cell panel) on IgA nephropathy risk was estimated to be 0.727 (95%CI: 0.624-0.847, p = 4.20e − 05, P FDR = 0.023) according to inverse variance weighting (IVW) method, and the weighted-median method yielded similar results (OR = 0.743, 95% CI: 0.596-0.927, p = 0.008). Although not statistically significant, the association was consistent with MR-Egger, simple mode and weighted mode. Conclusions Our study further confirmed that immune cells play a complex and important role in the pathogenesis of IgA nephropathy, providing evidence for clinical research.

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Immunological abnormalities in patient with IgA nephropathy

Cited by 3 publications

References 0 publications

Production of Interleukin-2 IL-2 and Expression of IL-2 Receptor in Patients with IgA Nephropathy

Production of Interleukin-2 IL-2 and Expression of IL-2 Receptor in Patients with IgA Nephropathy

Single-cell RNA-sequencing reveals distinct immune cell subsets and signaling pathways in IgA nephropathy

Causal role of immune cells in IgA nephropathy: a mendelian randomization study

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