The Emerging Role of Pathogenesis of IgA Nephropathy

Wu, Mengyu; Chen, Chien‐Sheng; Yiang, Giou‐Teng; Cheng, Pei‐Wen; Chen, Yulong; Chiu, Hsiao-Chen; Liu, Kuan-Hung; Lee, Wen‐Chin; Li, Chia-Jung

doi:10.3390/jcm7080225

Cited by 30 publications

(23 citation statements)

References 110 publications

(120 reference statements)

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“…Thus, isotype shifting from IgM to IgG in the lung likely exacerbates lupus pathogenesis. IgA AAbs might also have pathogenic roles, particularly in the context of glomerulonephritis [82,83]. While IgA nephropathy is the most common IgA-associated autoimmune disease [18], this isotype has been linked to other autoimmune diseases, including lupus [84][85][86].…”

Section: Discussionmentioning

confidence: 99%

Omega-3 fatty acid intake suppresses induction of diverse autoantibody repertoire by crystalline silica in lupus-prone mice

Rajasinghe

Zhu

et al. 2020

Autoimmunity

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Inhalation of crystalline silica (cSiO 2) in the workplace is etiologically linked to lupus and other autoimmune diseases. Exposing lupus-prone NZBWF1 mice to respirable cSiO 2 unleashes a vicious cycle of inflammation and cell death in the lung that triggers interferon-regulated gene expression, ectopic lymphoid structure (ELS) development, elevation of local and systemic autoantibodies (AAbs), and glomerulonephritis. However, cSiO 2-induced inflammation and onset of autoimmunity can be prevented by inclusion of the x-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) into the diet of these mice. Since cSiO 2 both causes cell death and interferes with efferocytosis, secondary necrosis of residual cell corpses might provide a rich and varied autoantigen (AAg) source in the lung. While it is known that the particle induces anti-nuclear and anti-dsDNA AAbs in NZBWF1 mice, the full extent of the cSiO 2-induced AAb response relative to specificity and isotype is not yet understood. The purpose of this study was to test the hypotheses that cSiO 2 exposure induces a wide spectrum of AAbs in the pulmonary and systemic compartments, and that dietary DHA intervention prevents these changes. Archived tissue fluid samples were obtained from a prior study in which NZBWF1 mice were fed purified isocaloric diets containing no DHA (control) or DHA corresponding calorically to human doses of 2 and 5 g/day. Mice were intranasally instilled with 1 mg cSiO 2 or saline vehicle weekly for 4 weeks, then groups euthanized 1, 5, 9, or 13 weeks post-instillation (PI) of the last cSiO 2 dose. Bronchoalveolar lavage fluid (BALF) and plasma from each time point were subjected to AAb profiling using a microarray containing 122 AAgs. cSiO 2 triggered robust IgG and IgM AAb responses against lupus-associated AAgs, including DNA, histones, ribonucleoprotein, Smith antigen, Ro/SSA, La/SSB, and complement as early as 1 week PI in BALF and 5 weeks PI in plasma, peaking at 9 and 13 weeks PI, respectively. Importantly, cSiO 2 also induced AAbs to AAgs associated with rheumatoid arthritis (collagen II, fibrinogen IV, fibrinogen S, fibronectin, and vimentin), Sj€ ogren's syndrome (a-fodrin), systemic sclerosis (topoisomerase I), vasculitis (MPO and PR3), myositis (Mi-2, TIF1-c, MDA5), autoimmune hepatitis (LC-1), and celiac disease (TTG). cSiO 2 elicited comparable but more modest IgA AAb responses in BALF and plasma. cSiO 2-induced AAb production was strongly associated with time dependent inflammatory/autoimmune gene expression, ELS development, and glomerulonephritis. AAb responses were dose-dependently suppressed by DHA supplementation and negatively correlated with the x-3 index, an erythrocyte biomarker of x-3 content in tissue phospholipids. Taken together, these findings suggest that cSiO 2 exposure elicits a diverse multi-isotype repertoire of AAbs, many of which have been reported in individuals with lupus and other autoimmune diseases. Furthermore, induction of this broad AAb spectrum could be impeded by increasing x-3 tissue content v...

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Section: Discussionmentioning

confidence: 99%

Omega-3 fatty acid intake suppresses induction of diverse autoantibody repertoire by crystalline silica in lupus-prone mice

Rajasinghe

Zhu

et al. 2020

Autoimmunity

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“…Studies have shown that the administration of LPS activates TLR4 receptors on mesangial cells, and causes the release of chemokines (CXCs), which promotes neutrophil infusion and the development of glomerulonephritis [114][115][116]. In addition, the IFN-γ and IFN-α responses induced by TLR activation induce overexpression of the B-cell activation factor (BAFF) in dendritic cells, favoring the expansion of B-cells and increasing IgA synthesis [117][118][119][120][121]. It was also shown that in kidney biopsies of patients with IgAN, CD19+/CD5+ B cell infiltration is present, which in the progressive forms of this disease produce significant amounts of IFN-γ and IgA and are more resistant to apoptosis compared to cells obtained from healthy donors [122,123].…”

Section: Iga Nephropathy (Igan)mentioning

confidence: 99%

Toll-Like Receptor as a Potential Biomarker in Renal Diseases

Mertowski

Lipa

Morawska

et al. 2020

IJMS

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One of the major challenges faced by modern nephrology is the identification of biomarkers associated with histopathological patterns or defined pathogenic mechanisms that may assist in the non-invasive diagnosis of kidney disease, particularly glomerulopathy. The identification of such molecules may allow prognostic subgroups to be established based on the type of disease, thereby predicting response to treatment or disease relapse. Advances in understanding the pathogenesis of diseases, such as membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, IgA (immunoglobulin A) nephropathy, and diabetic nephropathy, along with the progressive development and standardization of plasma and urine proteomics techniques, have facilitated the identification of an increasing number of molecules that may be useful for these purposes. The growing number of studies on the role of TLR (toll-like receptor) receptors in the pathogenesis of kidney disease forces contemporary researchers to reflect on these molecules, which may soon join the group of renal biomarkers and become a helpful tool in the diagnosis of glomerulopathy. In this article, we conducted a thorough review of the literature on the role of TLRs in the pathogenesis of glomerulopathy. The role of TLR receptors as potential marker molecules for the development of neoplastic diseases is emphasized more and more often, as prognostic factors in diseases on several epidemiological backgrounds.

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“…The B cell activation factor of TNF family (BAFF) and a proliferation-inducing ligand (APRIL) has been indicated as modulating factors of B cell in the IgA pathogenesis by reducing both IgA serum levels and IgA glomerular deposition. These molecules may represent intriguing therapeutic targets for new IgAN treatments (26).…”

Section: Iga Nephropathy In the Native Kidneymentioning

confidence: 99%

Immunoglobulin A Nephropathy. Recurrence After Renal Transplantation

et al. 2019

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IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. The disease generally runs an indolent course but may lead to ESRD in 20–30% of patients in 20 years or more after diagnosis. Patients with IgA nephropathy are ideal candidates for renal transplant because they are generally relatively young and with few comorbidities. Their graft survival is better or comparable to that of controls at 10 years, though few data are available after 10 years of follow-up. Recurrence of the original disease in the graft is a well-known complication of transplant in IgAN and is a significant cause of deterioration of graft function. Recurrent IgAN rarely manifests clinically before 3 years post transplantation. Recurrence rate is estimated to be around 30% with considerable differences among different series. Despite these factors there is no certain recurrence predictor, young age at renal transplant, rapid progression of the original disease and higher levels of circulating galactose-deficient IgA1 and IgA-IgG immune complexes are all associated with a higher rate of recurrence. Which pathogenetic mechanisms are responsible for the progression of the recurrence to graft function deterioration, and what therapy can prevent or slow down the progression of the disease in the graft, are open questions. The aim of this review is to describe the clinical outcome of renal transplantation in IgA patients with attention to the rate and the predictors of recurrence and to discuss the available therapeutic options for the management of recurrence.

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The Emerging Role of Pathogenesis of IgA Nephropathy

Cited by 30 publications

References 110 publications

Omega-3 fatty acid intake suppresses induction of diverse autoantibody repertoire by crystalline silica in lupus-prone mice

Omega-3 fatty acid intake suppresses induction of diverse autoantibody repertoire by crystalline silica in lupus-prone mice

Toll-Like Receptor as a Potential Biomarker in Renal Diseases

Immunoglobulin A Nephropathy. Recurrence After Renal Transplantation

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