Investigation the Pathology Role of O-glycosylation of IgA using a Nephritis Mouse Model

• Main Authors: LIU, PENG-SIN, 劉芃欣
• Other Authors: KA,SHUK-MAN
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/6h5rz9

碩士 === 國防醫學院 === 航太及海底醫學研究所 === 107 === IgA nephropathy (IgAN) is one of the major causes of chronic renal failure and uremia in young people worldwide. However, it still need do the renal biopsy for confirming the diagnosis. Some literatures mentioned that auto- antibodies such as IgG may be induced by the lacking galactose in the O-glycan of the IgA1 in the circulation of IgAN patients, and subsequent forming an IgG-IgA1 immune complexes. The immune complexes will deposit in the glomerular mesangial area with a variety of histopathologic injuries. Although the pathogenic mechanism underlying IgAN has yet to be determined, circulating IgA immune complexes is considered to act an important role in the development and progression of IgAN. Therefore, we (1) generated enzyme-treated galactose deficient IgA1 protein; (2) examined clearance kinetics of disappearances and tissues distribution of galactose deficient IgA1 using I125-labelled techniques in mouse; (3) detected protein levels of galactose deficient IgA in renal tissues by immunohistochemistry, and evaluated the relationship between the protein levels of galactose deficient IgA in IgAN patients and their distinct clinico-pathological severities. In present study, the results showed that (1) higher uptake levels of I125-labbled abnormal O-glycosylated IgA1 were detected in renal tissues, while uptake levels of I125-labbled normal O-glycosylated IgA1 in liver tissues with upward trend were observed; (2) protein expression levels of galactose deficient IgA significantly increased in the renal glomeruli of IgAN patients; (3) the magnitudes of galactose deficient IgA in renal tissues were significantly positively correlated to BUN, but negatively correlated to eGFR. We concluded that the abnormal O-glycosylated IgA1 is a key step directing IgA1 immune complex glomerular deposition in IgAN.