• HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
Thursday, July 31, 2025
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
  • HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
        • Lecturer
        • PhD Studentship
        • Postdoc
        • Research Assistant
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
No Result
View All Result
Bioengineer.org
No Result
View All Result
Home NEWS Science News Biology

Pivotal role found for IgG autoantibodies in IgA nephropathy

Bioengineer by Bioengineer
September 24, 2019
in Biology
Reading Time: 4 mins read
0
Share on FacebookShare on TwitterShare on LinkedinShare on RedditShare on Telegram

IgA nephropathy is the leading primary glomerulonephritis worldwide

IMAGE

Credit: UAB

BIRMINGHAM, Ala. – The most common form of the kidney disease called glomerulonephritis is IgA nephropathy.

IgA nephropathy is believed to be caused by IgA1-containing immune complexes formed in the blood that ultimately deposit in the glomeruli — the filtering apparatus of the kidneys. When kidney glomeruli become damaged, the kidneys lose their ability to remove waste from the blood and to retain blood proteins, and the injury can lead to kidney failure.

In IgA nephropathy kidney biopsies, IgA1 is the main immunoglobulin detected in the glomeruli by a clinical test called routine immunofluorescence. But those tests were often failing to detect immunoglobulin IgG, which was believed to be another vital contributor to the disease.

Now a study published in the Journal of the American Society of Nephrology by researchers at the University of Alabama at Birmingham largely validates the hypothesis that a second immunoglobulin, IgG, is a crucial part of the pathogenic immunodeposits in glomeruli of patients with IgA nephropathy. Up to now, routine immunofluorescence microscopy — which identifies the presence of IgA in all cases of IgA nephropathy — failed to show IgG in 50 to 80 percent of kidney biopsies. In addition, IgG found in those positive tests had never been tested for antigenic specificity, such as specificity against the IgA1.

UAB researchers hypothesized that the IgA1 was blocking the IgG from being detected in routine immunofluorescence microscopy, say co-corresponding authors Dana Rizk, M.D., and Jan Novak, Ph.D. When a different reagent, a small nanobody that detects the very end of the IgG molecule was used, IgG was detected in all biopsy specimens, including those that did not show IgG by routine immunofluorescence. Moreover, a highly sensitive confocal microscopy showed co-localization of the IgA1 and IgG in glomerular deposits of the biopsy-tissue specimens.

Furthermore, the IgG that UAB researchers extracted from both groups of biopsies specifically bound to the galactose-deficient IgA1, the glycoform of IgA1 that is known to be elevated in IgA nephropathy. The IgG autoantibody specific for galactose-deficient IgA1was not found in control extracts from two other forms of glomerulonephritis that do not involve galactose-deficient IgA1 — primary membranous nephropathy and lupus nephritis. These tests together confirmed that the IgG autoantibodies specific for galactose-deficient IgA1 are unique for immunodeposits of patients with IgA nephropathy.

“These results reveal, for the first time, that IgA nephropathy kidney biopsies, with or without IgG by routine immunofluorescence, contain IgG autoantibodies specific for galactose-deficient IgA1,” Novak said. “These findings support the importance of these autoantibodies in the pathogenesis of IgA nephropathy.”

“These IgG autoantibodies specific for galactose-deficient IgA1are present also in blood of patients with IgA nephropathy, and the autoantibody levels predict disease progression. Thus, we can measure these autoantibodies in blood to identify patients who could benefit from a future disease-specific therapy, or monitor patients for responses to the therapy,” Novak said. “And better understanding of these autoantibodies can help us to develop new, disease-specific treatments for IgA nephropathy.”

###

The study, Novak and Rizk say, largely validates the four-hit hypothesis of IgA nephropathy pathogenesis: 1) Patients with IgA nephropathy have elevated levels of circulatory galactose-deficient IgA1; 2) This leads to development of autoantibodies, mostly of the IgG subclass; 3) The IgG autoantibodies bind galactose-deficient IgA1 to form pathogenic immune complexes; and 4) Those pathogenic immune complexes deposit in glomeruli to incite kidney injury.

Further support for this hypothesis comes from multiple findings. For example, previous studies showed that IgA1 immunodeposits in IgA nephropathy are enriched for galactose-deficient IgA1, likely originating from the IgA1-IgG complexes formed in the circulation. This study thus provided a key piece of evidence for the pathogenic role of IgG autoantibodies in IgA nephropathy.

At UAB, Novak is professor in the UAB Department of Microbiology and Rizk is associate professor in the UAB Department of Medicine’s Division of Nephrology. She also directs clinical trials research in that division.

Co-authors with Rizk and Novak in the JASN paper, “Glomerular immunodeposits of patients with IgA nephropathy are enriched for IgG autoantibodies specific for galactose-deficient IgA1,” are Manish K. Saha and Bruce A. Julian, Division of Nephrology, UAB Department of Medicine; Stacy Hall, Rhubell Brown and Zhi-Qiang Huang, UAB Department of Microbiology; and Huma Fatima and Lea Novak, UAB Department of Pathology.

Jan Novak and Bruce Julian designed the study. Support came from National Institutes of Health grants DK078244 and DK082753, and from a gift from the IGA Nephropathy Foundation of America. Manish Saha had support from NIH T32 training grant DK07545.

Media Contact
Jeff Hansen
[email protected]

Original Source

https://www.uab.edu/news/research/item/10784-pivotal-role-found-for-igg-autoantibodies-in-iga-nephropathy

Related Journal Article

http://dx.doi.org/10.1681/ASN.2018111156

Tags: BiotechnologyDiagnosticsImmunology/Allergies/AsthmaInternal MedicineMedicine/HealthUrogenital System
Share12Tweet8Share2ShareShareShare2

Related Posts

Leopard Seals Sing: Under-Ice Sounds Flow Like Nursery Rhymes

Leopard Seals Sing: Under-Ice Sounds Flow Like Nursery Rhymes

July 31, 2025
blank

New Book Investigates How Antibiotics Affect Women’s Reproductive Health

July 31, 2025

Western Biologists Uncover Long-Standing Mystery Behind Cricket Song Mechanism

July 31, 2025

How ‘Scrumping’ Apes Might Have Sparked Our Craving for Alcohol

July 31, 2025
Please login to join discussion

POPULAR NEWS

  • Blind to the Burn

    Overlooked Dangers: Debunking Common Myths About Skin Cancer Risk in the U.S.

    60 shares
    Share 24 Tweet 15
  • Dr. Miriam Merad Honored with French Knighthood for Groundbreaking Contributions to Science and Medicine

    46 shares
    Share 18 Tweet 12
  • Study Reveals Beta-HPV Directly Causes Skin Cancer in Immunocompromised Individuals

    37 shares
    Share 15 Tweet 9
  • Engineered Cellular Communication Enhances CAR-T Therapy Effectiveness Against Glioblastoma

    35 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

Zinc Found in Blocked Syringes: A Closer Look at Contamination Sources

Landmark Bird Survey Reveals Rainforest Clearing for Cattle Farming Harms Nature More Than Expected

Scientists Uncover Why Optimal Transport Theory Excels in Generative Models

  • Contact Us

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
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.