AnatomyⅡ

大山 友香子

オオヤマ ユカコ  (Yukako Ohyama)

基本情報

所属
藤田医科大学 医学部 医学科 生体構造学 講師
学位
医学博士(2020年9月 藤田医科大学 医学部 医学研究科)

J-GLOBAL ID
202001000313786524
researchmap会員ID
R000007461

学歴

 2

論文

 11
  • Yukako Ohyama, Hisateru Yamaguchi, Soshiro Ogata, Samantha Chiurlia, Sharon N Cox, Nikoletta-Maria Kouri, Maria J Stangou, Kazuki Nakajima, Hiroki Hayashi, Daijo Inaguma, Midori Hasegawa, Yukio Yuzawa, Naotake Tsuboi, Matthew B Renfrow, Jan Novak, Aikaterini A Papagianni, Francesco P Schena, Kazuo Takahashi
    iScience 25(11) 105223-105223 2022年11月18日  
    Galactose (Gal)-deficient IgA1 (Gd-IgA1) is involved in IgA nephropathy (IgAN) pathogenesis. To reflect racial differences in clinical characteristics, we assessed disease- and race-specific heterogeneity in the O-glycosylation of the IgA1 hinge region (HR). We determined serum Gd-IgA1 levels in Caucasians (healthy controls [HCs], n = 31; IgAN patients, n = 63) and Asians (HCs, n = 20; IgAN patients, n = 60) and analyzed profiles of serum IgA1 HR O-glycoforms. Elevated serum Gd-IgA1 levels and reduced number of Gal residues per HR were observed in Caucasians. Reduced number of N-acetylgalactosamine (GalNAc) residues per HR and elevated relative abundance of IgA1 with three HR O-glycans were common features in IgAN patients; these features were associated with elevated blood pressure and reduced renal function. We speculate that the mechanisms underlying the reduced GalNAc content in IgA1 HR may be relevant to IgAN pathogenesis.
  • Katerina Zachova, Jana Jemelkova, Petr Kosztyu, Yukako Ohyama, Kazuo Takahashi, Josef Zadrazil, Jiri Orsag, Karel Matousovic, Dana Galuszkova, Nadezda Petejova, Jiri Mestecky, Milan Raska
    Journal of the American Society of Nephrology : JASN 33(5) 908-917 2022年5月  
    BACKGROUND: IgA nephropathy (IgAN) primary glomerulonephritis is characterized by the deposition of circulating immune complexes composed of polymeric IgA1 molecules with altered O-glycans (Gd-IgA1) and anti-glycan antibodies in the kidney mesangium. The mesangial IgA deposits and serum IgA1 contain predominantly λ light (L) chains, but the nature and origin of such IgA remains enigmatic. METHODS: We analyzed λ L chain expression in peripheral blood B cells of 30 IgAN patients, 30 healthy controls (HCs), and 18 membranous nephropathy patients selected as disease controls (non-IgAN). RESULTS: In comparison to HCs and non-IgAN patients, peripheral blood surface/membrane bound (mb)-Gd-IgA1+ cells from IgAN patients express predominantly λ L chains. In contrast, total mb-IgA+, mb-IgG+, and mb-IgM+ cells were preferentially positive for kappa (κ) L chains, in all analyzed groups. Although minor in comparison to κ L chains, λ L chain subsets of mb-IgG+, mb-IgM+, and mb-IgA+ cells were significantly enriched in IgAN patients in comparison to non-IgAN patients and/or HCs. In contrast to HCs, the peripheral blood of IgAN patients was enriched with λ+ mb-Gd-IgA1+, CCR10+, and CCR9+ cells, which preferentially home to the upper respiratory and digestive tracts. Furthermore, we observed that mb-Gd-IgA1+ cell populations comprise more CD138+ cells and plasmablasts (CD38+) in comparison to total mb-IgA+ cells. CONCLUSIONS: Peripheral blood of IgAN patients is enriched with migratory λ+ mb-Gd-IgA1+ B cells, with the potential to home to mucosal sites where Gd-IgA1 could be produced during local respiratory or digestive tract infections.
  • Yukako Ohyama, Masahiko Yazawa, Yoichiro Haji, Akihiro Ryuge, Naoho Takizawa, Atsushi Nomura, Hideaki Shimizu, Yoshiro Fujita
    Journal of nephrology 35(2) 687-688 2022年3月  
  • Yukako Ohyama, Hisateru Yamaguchi, Kazuki Nakajima, Tomohiro Mizuno, Yukihiro Fukamachi, Yasuto Yokoi, Naotake Tsuboi, Daijo Inaguma, Midori Hasegawa, Matthew B Renfrow, Jan Novak, Yukio Yuzawa, Kazuo Takahashi
    Scientific reports 11(1) 21209-21209 2021年10月21日  
  • Yukako Ohyama, Matthew B Renfrow, Jan Novak, Kazuo Takahashi
    Journal of clinical medicine 10(16) 2021年8月5日  
    IgA nephropathy (IgAN), the most common primary glomerular disease worldwide, is characterized by glomerular deposition of IgA1-containing immune complexes. The IgA1 hinge region (HR) has up to six clustered O-glycans consisting of Ser/Thr-linked N-acetylgalactosamine usually with β1,3-linked galactose and variable sialylation. Circulating levels of IgA1 with abnormally O-glycosylated HR, termed galactose-deficient IgA1 (Gd-IgA1), are increased in patients with IgAN. Current evidence suggests that IgAN is induced by multiple sequential pathogenic steps, and production of aberrantly glycosylated IgA1 is considered the initial step. Thus, the mechanisms of biosynthesis of aberrantly glycosylated IgA1 and the involvement of aberrant glycoforms of IgA1 in disease development have been studied. Furthermore, Gd-IgA1 represents an attractive biomarker for IgAN, and its clinical significance is still being evaluated. To elucidate the pathogenesis of IgAN, it is important to deconvolute the biosynthetic origins of Gd-IgA1 and characterize the pathogenic IgA1 HR O-glycoform(s), including the glycan structures and their sites of attachment. These efforts will likely lead to development of new biomarkers. Here, we review the IgA1 HR O-glycosylation in general and the role of aberrantly glycosylated IgA1 in the pathogenesis of IgAN in particular.

MISC

 17

共同研究・競争的資金等の研究課題

 3