Fibrillary glomerulonephritis is a glomerular disease historically defined by glomerular deposition of Congo red-negative, randomly oriented straight fibrils that lack a hollow center and stain with antisera to immunoglobulins. It was initially considered to be an idiopathic disease, but recent studies highlighted association in some cases with autoimmune disease, malignant neoplasm, or hepatitis C viral infection. Prognosis is poor with nearly half of patients progressing to end-stage renal disease within 4 years. There is currently no effective therapy, aside from kidney transplantation, which is associated with disease recurrence in a third of cases. The diagnosis has been hampered by the lack of biomarkers for the disease and the necessity of electron microscopy for diagnosis, which is not widely available. Recently, through the use of laser microdissection-assisted liquid chromatography-tandem mass spectrometry, a novel biomarker of fibrillary glomerulonephritis, DnaJ homolog subfamily B member 9, has been identified. Immunohistochemical studies confirmed the high sensitivity and specificity of DnaJ homolog subfamily B member 9 for this disease; dual immunofluorescence showed its colocalization with IgG in glomeruli; and immunoelectron microscopy revealed its localization to individual fibrils of fibrillary glomerulonephritis. The identification of this tissue biomarker has already entered clinical practice and undoubtingly will improve the diagnosis of this rare disease, particularly in developing countries where electron microscopy is less available. Future research is needed to determine whether DnaJ homolog subfamily B member 9 is an autoantigen or just an associated protein in fibrillary glomerulonephritis, whether it can serve as a noninvasive biomarker, and whether therapies that target this protein are effective in improving prognosis.
Keywords: Congo red; DNAJB9; DnaJ homolog subfamily B member 9; fibrillary glomerulonephritis; mass spectrometry; tissue biomarker.
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