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Potential Autoantigen Identified in Aggressive Kidney Disease

By Labmedica International staff writers
Posted on 13 Nov 2017
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Image: An immunohistochemistry of the new biomarker DNAJB9 greatly improves diagnostic sensitivity for the rare kidney disease, fibrillary glomerulonephritis (Photo courtesy of Mayo Clinic).
Image: An immunohistochemistry of the new biomarker DNAJB9 greatly improves diagnostic sensitivity for the rare kidney disease, fibrillary glomerulonephritis (Photo courtesy of Mayo Clinic).
Fibrillary glomerulonephritis (FGN) is an aggressive kidney disease, and nearly half of patients become dependent on dialysis within several years of diagnosis. No unique clinical markers of FGN have been identified to help diagnose FGN, and current tests involve time-consuming analyses with light microscopy, immunofluorescence, and electron microscopy.

Once a diagnosis of FGN is made, most patients are treated non-specifically with immunosuppressive therapy, which is often not effective and can be associated with significant adverse effects. The presence of abundant levels of a certain protein in the kidneys of patients with fibrillary glomerulonephritis (FGN) has been discovered. In FGN, large amounts of this protein become trapped in the millions of filtering units or glomeruli that make up the kidney.

Working independently scientists from the Mayo Clinic (Rochester, MN, USA) and the University of Washington (Seattle, WA, USA) analyzed the protein content of glomeruli in patient biopsy specimens. The latter group isolated glomeruli from formalin-fixed and paraffin-embedded biopsy specimens using laser capture microdissection and analyzed them with liquid chromatography and data-dependent tandem mass spectrometry. The Mayo clinic team analyzed the proteomic content of glomeruli in patient biopsy specimens.

Both groups detected DnaJ heat shock protein family member B9 (DNAJB9) as an abundant protein in FGN glomeruli, but not in glomeruli from healthy individuals. An accumulation of antibodies was also found along with DNAJB9 in glomeruli from patients with FGN, suggesting that DNAJB9 and antibodies that are likely directed against the protein contribute to the glomerular deposits that are a hallmark of FGN. The resulting new DNAJB9 immunohistochemistry (IHC) test is highly sensitive (98%) and specific (99.7%) to FGN. Therefore, DNAJB9 may be an autoantigen, or a normal protein that is the target of an autoimmune response.

Samih Nasr, MD, co–senior author of the Mayo study, said, “Now that we know that large amounts of this protein are deposited in the kidneys of patients with FGN, future therapies that reduce the rate of deposition of this protein in the treatment of this intriguing disease.” Kelly Smith, MD, PhD, the senior author of the University of Washington study, added, “The discovery of DNAJB9 as a putative autoantigen in FGN paves the way for the development of new diagnostic and therapeutic tools to help care for patients with this disease.” The studies were published on November 2, 2017, in the Journal of the American Society of Nephrology.

Related Links:
Mayo Clinic
University of Washington

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