Mayo Clinic Laboratory and pathology research roundup: November 16
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The research roundup provides an overview of the past week’s research from Mayo Clinic Laboratories consultants, including featured abstracts and a complete list of published studies and reviews.
Featured Abstract
Discovery of autoantibodies targeting nephrin in minimal change disease supports a novel autoimmune etiology.
Background Failure of the glomerular filtration barrier, primarily by loss of slit diaphragm architecture, underlies nephrotic syndrome in minimal change disease. The etiology remains unknown. The efficacy of B cell-targeted therapies in some patients, together with the known proteinuric effect of antinephrin antibodies in rodent models, prompted us to hypothesize that nephrin autoantibodies may be present in patients with minimal change disease. Methods We evaluated sera from patients with minimal change disease enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) cohort and from our own institutions for circulating nephrin autoantibodies by indirect ELISA and by immunoprecipitation of full-length nephrin from human glomerular extract or a recombinant purified extracellular domain of human nephrin. We also evaluated renal biopsies from our institutions for podocyte-associated punctate IgG colocalizing with nephrin by immunofluorescence Results In two independent patient cohorts, we identified in a subset of patients with minimal change disease circulating nephrin autoantibodies during active disease that were significantly reduced or absent during treatment response. We correlated the presence of these autoantibodies with podocyte-associated punctate IgG in renal biopsies from our institutions. We also identified a patient with steroid-dependent childhood minimal change disease that progressed to end-stage kidney disease; she developed a massive posttransplant recurrence of proteinuria that was associated with high pretransplant circulating nephrin autoantibodies. Conclusions Our discovery of nephrin autoantibodies in a subset of adults and children with minimal change disease aligns with published animal studies and provides further support for an autoimmune etiology. We propose a new molecular classification of nephrin autoantibody minimal change disease to serve as framework for instigation of precision therapeutics for these patients.
Published to PubMed This Week
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encephalitis is a cytokine release syndrome: evidences from cerebrospinal fluid analyses.
Clinical Infectious Diseases - Home self-collection and specimen pooling: tools for convenient and economical detection of sexually transmitted infections.
Clinical Infectious Diseases - Decrease in enteroviral meningitis: an unexpected benefit of coronavirus disease 2019 (COVID-19) mitigation?
Clinical Infectious Diseases - Enzalutamide-induced and PTH1R-mediated TGFBR2 degradation in osteoblasts confers resistance in prostate cancer bone metastases.
Cancer Letters - Implementation of a comprehensive patient blood management program for hospitalized patients at a large United States medical center.
Mayo Clinic Proceedings - SARS-CoV-2 testing before international airline travel, December 2020 to May 2021.
Mayo Clinic Proceedings - On the road back to normalcy: following science over noise in SARS-CoV-2.
Mayo Clinic Proceedings - Uterine epithelioid trophoblastic tumor.
Mayo Clinic Proceedings - Pharmacogenomics testing in patients with liver transplant and potential impact on prospective management.
Pharmacogenomics - Immune checkpoint inhibitor-induced thyroiditis Is associated with increased intrathyroidal T lymphocyte subpopulations.
Thyroid
