DNA Methylation in Cosmc Promoter Region and Aberrantly Glycosylated IgA1 Associated with Pediatric IgA Nephropathy

Sun, Qiang; Zhang, Jianqian; Zhou, Nan; Liu, Xiaorong; Shen, Ying

doi:10.1371/journal.pone.0112305

Cited by 28 publications

(31 citation statements)

References 26 publications

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“…Upper respiratory tract infections and tonsillitis are also among the clinical manifestations seen in IgAN patients. Infections are correlated with disease onset or exacerbations . Interestingly, C1GALT1C1 levels are further diminished with more pronounced glycosylation defects detected in IgA1‐positive a human B lymphoma cell line and in an IgAN patient blood and tonsillar lymphocytes upon LPS, α‐hemolytic Streptococcus and Helicobacter pilori stimulation .…”

Section: The Immunological Impact Of Glycosylation Defects—an Update mentioning

confidence: 99%

CDG and immune response: From bedside to bench and back

Pascoal

Francisco

Ferro

et al. 2019

J of Inher Metab Disea

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Glycosylation is an essential biological process that adds structural and functional diversity to cells and molecules, participating in physiological processes such as immunity. The immune response is driven and modulated by protein‐attached glycans that mediate cell‐cell interactions, pathogen recognition and cell activation. Therefore, abnormal glycosylation can be associated with deranged immune responses. Within human diseases presenting immunological defects are congenital disorders of glycosylation (CDG), a family of around 130 rare and complex genetic diseases. In this review, we have identified 23 CDG with immunological involvement, characterized by an increased propensity to—often life‐threatening—infection. Inflammatory and autoimmune complications were found in 7 CDG types. CDG natural history(ies) and the mechanisms behind the immunological anomalies are still poorly understood. However, in some cases, alterations in pathogen recognition and intracellular signaling (eg, TGF‐β1, NFAT, and NF‐κB) have been suggested. Targeted therapies to restore immune defects are only available for PGM3‐CDG and SLC35C1‐CDG. Fostering research on glycoimmunology may elucidate the involved pathophysiological mechanisms and open new therapeutic avenues, thus improving CDG patients' quality of life.

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Section: The Immunological Impact Of Glycosylation Defects—an Update mentioning

confidence: 99%

CDG and immune response: From bedside to bench and back

Pascoal

Francisco

Ferro

et al. 2019

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

“…Interestingly, even though the elevation of Cosmc mRNA levels it induces is more significant in IgAN patients, the decrease it causes in Cosmc promoter methylation is less remarkable in the IgAN group in comparison to the other two groups. Furthermore, in the IgAN group (conversely to the other two) there is a very strong negative correlation between Cosmc DNA methylation and Cosmc mRNA expression, thus indicating that the degree of methylation could possibly be a crucial element in the regulation of the mRNA levels [16]. However, according to Sun et al [16] results, Cosmc promoter methylation is not significantly different in IgAN patients compared to controls, possibly suggesting that Cosmc mRNA production is not determined by the level of methylation of the promoter, but by the change in the methylation status.…”

Section: Dna Methylationmentioning

confidence: 95%

“…Decreased Cosmc expression has been linked to IgA1-aberrant glycosylation observed in IgAN [14,15]. Sun et al [16] investigated the methylation levels of CpG islands (CGIs) of the Cosmc gene promoter as a possible factor involved in its downregulation. In their research, they proved that Interleukin 4 (IL-4) enhances the divergence in Cosmc mRNA levels between IgAN patients (who already demonstrate lower Cosmc mRNA expression) and healthy subjects or patients with other renal diseases.…”

Section: Dna Methylationmentioning

confidence: 99%

Epigenetics of IgA Nephropathy: A Brief Review

Stai¹

2018

obm genet

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Immunoglobin A Nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Its development is characterized by the deposition of immune complexes that consist of abnormally galactosylated IgA1 molecules and IgG or IgA autoantibodies in the mesangium and the subsequent induction of renal injury. Recent research has shed light to many aspects of the pathogenesis of the disease, including the contribution of epigenetic modifications in its onset and progression. This review aims to present some of the most important epigenetic mechanisms mediating IgA1 development, including alterations in DNA methylation and histone modifications. Though a lot of progress has been made in this field, there is still much to be uncovered to have full understanding the full understanding of the epigenetics involved in IgAN, which can finally lead to a new, more promising approach to IgAN patients.

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“…Cosmc is essential for galactosyltransferase activity. Therefore, elevated levels of galactose-deficient glycans are produced [ 19 ]. Microbiota dysbiosis leads to increased production of IgA and in particular, galactose deficient IgA.…”

Section: Reviewmentioning

confidence: 99%

Progress in Pathogenesis of Immunoglobin A Nephropathy

Stanley¹,

Deng²

2020

Cureus

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The understanding of the pathogenesis of any disease is the key to effective and specific treatment of the disease. immunoglobulin A (IgA) nephropathy is an autoimmune disease of the kidney. Oxford MEST classification is commonly used to stratify patients according to the severity of the disease. Patients with IgA nephropathy seem to produce anti-GalNAc antibodies against a particularly defective IgA1. This immune complex deposits in the kidneys, leading to a type 3 hypersensitivity reaction which ultimately damages the kidneys. People of a certain genetic background and who experience upregulation of certain defective receptors seem to develop primary IgA nephropathy. Secondary IgA nephropathy could be due to dysbiosis of the microbiota in the gut, compromised gut immunity or other gut pathologies, pulmonary function abnormalities, or amyloidosis. Overproduction of IgA due to plasma cell dyscrasia or reduced clearance of IgA due to liver abnormalities could also be potential causes. Genes that predispose individuals to IgA nephropathy and intestinal abnormalities, such as Celiac disease, seem to overlap and these people tend to have a poorer prognosis and need to be placed on more intensive treatment regimens. IgA Vasculitis seems to be a systemic form of IgA nephropathy, whereby IgA deposits systemically and leads to multiple disease manifestations. Patients in high-risk groups could also be prophylactically screened for the disease and closely monitored by immunohistochemical methods such as an enzyme-linked immunosorbent assay (ELISA) or identified by genetic testing. Currently, the major treatment regimens involve supportive therapy or immunosuppressive therapy which has major side effects. More specific treatment methods such as monoclonal antibodies, immunoglobulin replacement therapy, or low-antigen-content diet could also be looked into as potential treatment options. Stem cell replacement, by way of bone marrow transplant and tonsillectomy, has been suggested as a treatment option in patients with indications.

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DNA Methylation in Cosmc Promoter Region and Aberrantly Glycosylated IgA1 Associated with Pediatric IgA Nephropathy

Cited by 28 publications

References 26 publications

CDG and immune response: From bedside to bench and back

CDG and immune response: From bedside to bench and back

Epigenetics of IgA Nephropathy: A Brief Review

Progress in Pathogenesis of Immunoglobin A Nephropathy

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