Autoantigens PLA2R and THSD7A in membranous nephropathy share a common epitope motif in the N-terminal domain.

Journal of Autoimmunity
Maryline FresquetPaul E Brenchley

Abstract

Patients with membranous nephropathy have autoantibodies against PLA2R (up to 80%), or THSD7A (up to 2%). We previously described the immunodominant epitope within PLA2R but epitopes in THSD7A are still unknown. To find anti-THSD7A sera for this study, we screened 1843 sera from biopsy-proven MN patients by ELISA and identified 22 sera as anti-THSD7A positive representing 1.2% of MN cases. Anti-THSD7A positive sera were further characterized by western blotting and slot blotting on THSD7A protein fragments and peptides. Real time interaction analyses and antibodies off-rate could be reliably determined using bio-layer interferometry. A signature motif in the N-terminal domain of THSD7A (T28mer) with sequence homology to the major PLA2R epitope (P28mer) was identified. B-cell epitope prediction analysis and homology modelling revealed this sequence to be antigenic and surface available suggesting it is accessible for the antibody to bind. All ten selected sera bound to the T28mer confirming this sequence as a dominant epitope in THSD7A. Reactivity to this sequence was lost following kallikrein protease cleavage within the predicted epitope. Importantly, cross-reactivity of both PLA2R and THSD7A autoantibodies was observed at the...Continue Reading

Citations

Jul 31, 2020·Clinical Reviews in Allergy & Immunology·Carlo Selmi
Dec 4, 2019·Frontiers in Medicine·Paolo CravediOriol Bestard
Sep 13, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Scott TaylorAthanasios Didangelos
Apr 4, 2021·Biomolecules·Yan GuDamu Tang
Apr 30, 2021·Néphrologie & thérapeutique·Jens Lutz
Jul 11, 2021·Journal of the Formosan Medical Association = Taiwan Yi Zhi·Shan-Shan LiYong Dai

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy
ELISA
PCR
surface plasmon resonance
chip
circular dichroism
biopsies

Clinical Trials Mentioned

NCT01180036

Software Mentioned

BepiPred
BeStSel
PEP
BLAST
Phyre
iProt
Sub Protease Specificity Prediction
Softmax
Sub
BepiPred -

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.