• HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
  • CONTACT US
Friday, September 22, 2023
BIOENGINEER.ORG
No Result
View All Result
  • Login
  • HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
        • Lecturer
        • PhD Studentship
        • Postdoc
        • Research Assistant
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
  • CONTACT US
  • HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
        • Lecturer
        • PhD Studentship
        • Postdoc
        • Research Assistant
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
  • CONTACT US
No Result
View All Result
Bioengineer.org
No Result
View All Result
Home NEWS Science News Health

Discovery of anti-mesangial autoantibodies redefines the pathogenesis of IgA nephropathy

Bioengineer by Bioengineer
March 22, 2023
in Health
Reading Time: 5 mins read
0
Share on FacebookShare on TwitterShare on LinkedinShare on RedditShare on Telegram

IgA nephropathy (IgAN) is a kidney disorder characterized by the buildup of immunoglobin A (IgA) in the glomeruli, which are bundles of capillaries that filter blood in the kidney. In advanced stages of the disease, the buildup of IgA in the glomeruli disrupts kidney functioning and, in approximately 30% to 40% of cases, leads to kidney failure. IgA is thought to form complexes with IgG, IgM, and C3 proteins in the blood and then accumulate in the glomeruli during filtration. However, the accepted explanation does not explain a unique hallmark of the disease: during the initial stages of IgAN, IgA deposition is seen in the mesangium, an area composed of mesangial cells and matrix within the glomerulus.

Pathogenesis of IgA nephropathy revealed in this study.

Credit: Daisuke Kitamura from TUS, Japan

IgA nephropathy (IgAN) is a kidney disorder characterized by the buildup of immunoglobin A (IgA) in the glomeruli, which are bundles of capillaries that filter blood in the kidney. In advanced stages of the disease, the buildup of IgA in the glomeruli disrupts kidney functioning and, in approximately 30% to 40% of cases, leads to kidney failure. IgA is thought to form complexes with IgG, IgM, and C3 proteins in the blood and then accumulate in the glomeruli during filtration. However, the accepted explanation does not explain a unique hallmark of the disease: during the initial stages of IgAN, IgA deposition is seen in the mesangium, an area composed of mesangial cells and matrix within the glomerulus.

In a study that was recently published in Science Advances, a group of researchers from Japan has uncovered the reason for IgA deposition being restricted to the mesangium. The researchers, including Professor Daisuke Kitamura from Tokyo University of Science and Dr. Yoshihito Nihei and Professor Yusuke Suzuki from Juntendo University, investigated the development of IgAN using specially bred mice, called gddY mice, which exhibit a disease similar to human IgAN.

The researchers found that unlike the serum of control mice that did not develop IgAN, the serum of gddY mice contained autoantibodies (antibodies that attack the cells of one’s own body) that recognize a protein called βII-spectrin found in the mesangial cells. “We have demonstrated that βII-spectrin, previously thought to be an intracellular protein, is in fact exposed on the surface of mesangial cells and directly recognized by the IgA autoantibodies produced by gddY mice. Similarly, anti-βII-spectrin IgA antibodies were found in the sera of many patients with IgAN,” explains lead researcher Prof. Kitamura.

The researchers conducted serum analyses, which revealed that a whopping 70% of the gddY mice produced IgA autoantibodies, whereas only 6% of the control mice were found to have them. Similarly, while about 60% of patients with IgAN tested in the study produced autoantibodies to βII-spectrin, none of the individuals in the control group had them. The researchers further discovered that cells producing IgA antibody called IgA+ plasmablasts accumulated in the kidneys of gddY mice and patients with IgAN.

To determine whether IgA autoantibodies specifically recognize and bind to βII-spectrin, the researchers introduced βII-spectrin in embryonic kidney-derived cell line and analyzed by flow cytometry, a laser-mediated analysis of immunofluorescence-stained cells. The result confirmed that the IgA autoantibodies did indeed bind specifically to βII-spectrin on the cell surface. The researchers further confirmed their findings by injecting mice with IgA autoantibodies and visualizing the structures of the glomeruli in kidney using immunofluorescence staining. “IgA antibodies isolated from gddY mice bound to βII-spectrin on the surface of mesangial cells, and when administered intravenously, bound to the renal mesangial cells. Thus, this study showed for the first time that IgA-type autoantibody production against mesangial cells may be the cause of IgAN,” Prof. Kitamura notes.

Understanding the mechanism of initial disease development in IgAN can help design better treatments for the disease in the future. Moreover, the findings of this study can make testing for IgAN easier than ever before. “Until now, IgAN could only be diagnosed by risky kidney biopsy. Now that we know that 36% to 60% of IgAN patients have IgA-type autoantibodies to beta 2-spectrin in their blood, we will be able to diagnose IgAN using the patient’s blood,” Prof. Kitamura concludes.

 

***

 

Reference                    

DOI: https://doi.org/10.1126/sciadv.add6734

Authors: Yoshihito Nihei1,2, Kei Haniuda2†, Mizuki Higashiyama2, Shohei Asami2, Hiroyuki Iwasaki1,2, Yusuke Fukao1, Maiko Nakayama1, Hitoshi Suzuki1, Mika Kikkawa3, Saiko Kazuno3, Yoshiki Miura3, Yusuke Suzuki1, Daisuke Kitamura2

Affiliations:

1Department of Nephrology, Juntendo University Faculty of Medicine

2Division of Cancer Cell Biology, Research Institute for Biomedical Sciences, Tokyo University of Science

3Laboratory of Proteomics and Biomolecular Science, Biomedical Research Core Facilities, Juntendo University Graduate School of Medicine

 

Further information

Prof. Daisuke Kitamura

Division of Cancer Cell Biology, Research Institute for Biomedical Sciences

Tokyo University of Science

Email: [email protected]

 

Prof. Yusuke Suzuki

Department of Nephrology

Juntendo University Faculty of Medicine

Email: [email protected]

 

 

Media contact

Hiroshi Matsuda

Public Relations Division

Tokyo University of Science

Email: [email protected]

Website: https://www.tus.ac.jp/en/mediarelations/

 

 

Public Relations Division

Juntendo University

E-mail: [email protected]

Website: https://en.juntendo.ac.jp/

 

 

Funding information: This work was supported by the Japan Society for the Promotion of Science KAKENHI, 720 Grant-in-Aid for Scientific Research (A) 20H00510 (D.K.).



Journal

Science Advances

DOI

10.1126/sciadv.add6734

Method of Research

Observational study

Subject of Research

Animal tissue samples

Article Title

Identification of IgA autoantibodies targeting mesangial cells redefines the pathogenesis of IgA nephropathy

Article Publication Date

22-Mar-2023

COI Statement

Yusuke Suzuki, Yoshihito Nihei, and Daisuke Kitamura are inventors on patent application (PCT/JP2021/044409) submitted by Juntendo Educational Foundation and Tokyo University of Science Foundation that covers “Autoantibodies related to IgA nephropathy.” All other authors declare they have no competing interests.

Share12Tweet8Share2ShareShareShare2

Related Posts

inside cover image

One-stop implementation from signal detection to processing

September 22, 2023
Ochsner Medical Center - New Orleans

Ochsner offers tuition assistance to aspiring nurses and doctors

September 22, 2023

Study shows millions of people live with co-occuring chronic pain and mental health symptoms

September 21, 2023

Scientists reveal intricate mechanisms cells use to build protein destruction signals

September 21, 2023

POPULAR NEWS

  • blank

    Microbe Computers

    58 shares
    Share 23 Tweet 15
  • University of South Florida scientist: Barnacles may help reveal location of lost Malaysia Airlines flight MH370

    46 shares
    Share 18 Tweet 12
  • Lithuanian invention at the forefront of solar technology breakthrough

    41 shares
    Share 16 Tweet 10
  • A pioneering study from Politecnico di Milano sheds light on one of the still poorly understood aspects of cancer

    34 shares
    Share 14 Tweet 9

About

We bring you the latest biotechnology news from best research centers and universities around the world. Check our website.

Follow us

Recent News

One-stop implementation from signal detection to processing

Australian research leads to clinical trial for rare women’s cancers

Ochsner offers tuition assistance to aspiring nurses and doctors

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

Join 57 other subscribers
  • Contact Us

Bioengineer.org © Copyright 2023 All Rights Reserved.

No Result
View All Result
  • Homepages
    • Home Page 1
    • Home Page 2
  • News
  • National
  • Business
  • Health
  • Lifestyle
  • Science

Bioengineer.org © Copyright 2023 All Rights Reserved.

Welcome Back!

Login to your account below

Forgotten Password?

Retrieve your password

Please enter your username or email address to reset your password.

Log In