C1GALT1 expression is associated with galactosylation of IgA1 in peripheral B lymphocyte in immunoglobulin a nephropathy

Abstract

Background: More and more studies demonstrated that genetic variation at C1GALT1 influences Gd-IgA1 level in IgAN. However, whether the expression of β1, 3-galactosyltransferase (β1, 3Gal-T) was influenced may provide insights into how Gd-IgA1 levels are controlled in IgAN. Methods: Thirty IgAN patients diagnosed in Tianjin Medical University General Hospital from April to September 2018 and 30 healthy volunteers whose age and gender matched with patients were enrolled in this study. Total Gd-IgA1 levels in plasma were determined by ELISA and C1GALT1 levels were determined by RT-PCR. Four databases (PubMed, EMBASE, CNKI, WanFang Medical Network) were searched to identify eligible studies that evaluated a difference in the expression of C1GALT1 in IgAN patients compared with total controls (non-IgAN and health controls). The C1GALT1C1 expression levels, which was indispensable to β1, 3Gal-T of IgA1, was also been compared. Results: Gd-IgA1 levels were remarkable higher in IgAN patients compared with healthy control. The expression levels of C1GALT1 gene were remarkably down-regulated in IgAN patients compared with healthy control. And the mRNA level of C1GALT1 was inversely correlated to Gd-IgA1 levels. In meta-analysis, six articles including 316 participants that analyzed the expression of β1, 3Gal-T were met inclusion criteria. There was no significant difference in the expression of C1GALT1 between IgAN patients compared with controls. And we found patients with IgAN had lower levels of C1GALT1 gene expression in the B cells compared to controls. The C1GALT1C1 levels in the IgAN patients were not different from the levels in the control group, which were unchanged no matter according to different ethnic population, different control group and different cell source. Two studies including 46 persons compared enzymatic activity of β1, 3Gal-T in B cells, and the result showed the β1, 3Gal-T activity was decreased in B cells. Conclusions: We found expression levels of C1GALT1 were remarkably downregulated in IgAN patients and negatively correlated with higher levels of Gd-IgA1. Subsequent meta-analysis validated the low expression and activity of β1, 3Gal-T in B cells in patients with IgAN. However, there was no apparent disparity in the aspect of C1GALT1C1 expression between IgAN and control groups.

C1GALT1 in health and disease (Review)

“…Kiryluk et al ( 57 ) used in vitro small interfering (si)RNA knockdown to demonstrate that C1GALT1 can determine the secretion rate of Gd-IgA1 in serum IgA1-producing cells. Xing et al ( 58 ) discovered that C1GALT1 expression in peripheral B lymphocytes of patients with IgAN has a negative correlation with increased Gd-IgA1 levels and is markedly downregulated compared with the increase of Gd-IgA1 level. The aforementioned study involved 30 patients with IgAN and 30 healthy volunteers in China ( 58 ).…”

“…Xing et al ( 58 ) discovered that C1GALT1 expression in peripheral B lymphocytes of patients with IgAN has a negative correlation with increased Gd-IgA1 levels and is markedly downregulated compared with the increase of Gd-IgA1 level. The aforementioned study involved 30 patients with IgAN and 30 healthy volunteers in China ( 58 ). Gd-IgA1 level was measured by an enzyme-linked immunosorbent assay, and the results revealed that Gd-IgA1 levels ranged between 8.55 and 14.48 U/ml in patients with IgAN and between 3.97 and 12.15 U/ml in healthy controls ( 58 ).…”

“…The aforementioned study involved 30 patients with IgAN and 30 healthy volunteers in China ( 58 ). Gd-IgA1 level was measured by an enzyme-linked immunosorbent assay, and the results revealed that Gd-IgA1 levels ranged between 8.55 and 14.48 U/ml in patients with IgAN and between 3.97 and 12.15 U/ml in healthy controls ( 58 ). In comparison with those in healthy controls, Gd-IGA1 levels were determined to be significantly higher in patients with IgAN (P < 0.001) ( 58 ).…”

“…Gd-IgA1 level was measured by an enzyme-linked immunosorbent assay, and the results revealed that Gd-IgA1 levels ranged between 8.55 and 14.48 U/ml in patients with IgAN and between 3.97 and 12.15 U/ml in healthy controls ( 58 ). In comparison with those in healthy controls, Gd-IGA1 levels were determined to be significantly higher in patients with IgAN (P < 0.001) ( 58 ). By reverse transcription-quantitative PCR, the expression levels of C1GALT1 were detected in peripheral B lymphocytes of both patients with IgAN and healthy controls, revealing that C1GALT1 expression was significantly downregulated in patients with IgAN compared with that in healthy controls (P=0.04) ( 58 ).…”

“…In comparison with those in healthy controls, Gd-IGA1 levels were determined to be significantly higher in patients with IgAN (P < 0.001) ( 58 ). By reverse transcription-quantitative PCR, the expression levels of C1GALT1 were detected in peripheral B lymphocytes of both patients with IgAN and healthy controls, revealing that C1GALT1 expression was significantly downregulated in patients with IgAN compared with that in healthy controls (P=0.04) ( 58 ). It has been suggested that a decrease in C1GALT1 expression in B lymphocytes may contribute to the increased production of Gd-IgA1 and eventually lead to IgAN pathogenesis ( 59 ).…”