-
J. Am. Soc. Nephrol. · Jan 2020
Clinical Relevance of Domain-Specific Phospholipase A2 Receptor 1 Antibody Levels in Patients with Membranous Nephropathy.
- Linda Reinhard, Gunther Zahner, Stephan Menzel, Friedrich Koch-Nolte, StahlRolf A KRAKIII. Department of Medicine and ehoxha@uke.de rstahl@uke.de., and Elion Hoxha.
- III. Department of Medicine and.
- J. Am. Soc. Nephrol. 2020 Jan 1; 31 (1): 197-207.
BackgroundAntibodies against phospholipase A2 receptor 1 (PLA2R1) are found in 80% of patients with membranous nephropathy, and previous studies described three autoantibody-targeted PLA2R1 epitope regions. Although anti-PLA2R1 antibody levels are closely associated with treatment response and disease prognosis, the clinical role of epitope regions targeted by autoantibodies is unclear.MethodsIn a prospective cohort of 150 patients with newly diagnosed PLA2R1-associated membranous nephropathy, we investigated the clinical role of epitope-recognition patterns and domain-specific PLA2R1 antibody levels by western blot and ELISA.ResultsWe identified a fourth epitope region in the CTLD8 domain of PLA2R1, which was recognized by anti-PLA2R1 antibodies in 24 (16.0%) patients. In all study patients, anti-PLA2R1 antibodies bound both the N-terminal (CysR-FnII-CTLD1) region and the C-terminal (CTLD7-CTLD8) region of PLA2R1 at study enrollment. The total anti-PLA2R1 antibody levels of patients determined detection of domain-specific PLA2R1 antibodies, and thereby epitope-recognition patterns. A remission of proteinuria occurred in 133 (89%) patients and was not dependent on the domain-recognition profiles. A newly developed ELISA showed that domain-specific PLA2R1 antibody levels targeting CysR, CTLD1, and CTLD7 strongly correlate with the total anti-PLA2R1 antibody level (Spearman's rho, 0.95, 0.64, and 0.40; P<0.001, P<0.001, and P=0.002, respectively) but do not predict disease outcome independently of total anti-PLA2R1 antibody levels.ConclusionsAll patients with PLA2R1-associated membranous nephropathy recognize at least two epitope regions in the N- and C-terminals of PLA2R1 at diagnosis, contradicting the hypothesis that PLA2R1 "epitope spreading" determines the prognosis of membranous nephropathy. Total anti-PLA2R1 antibody levels, but not the epitope-recognition profiles at the time of diagnosis, are relevant for the clinical outcome of patients with this disease.Copyright © 2020 by the American Society of Nephrology.
Notes
Knowledge, pearl, summary or comment to share?You can also include formatting, links, images and footnotes in your notes
- Simple formatting can be added to notes, such as
*italics*
,_underline_
or**bold**
. - Superscript can be denoted by
<sup>text</sup>
and subscript<sub>text</sub>
. - Numbered or bulleted lists can be created using either numbered lines
1. 2. 3.
, hyphens-
or asterisks*
. - Links can be included with:
[my link to pubmed](http://pubmed.com)
- Images can be included with:
![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
- For footnotes use
[^1](This is a footnote.)
inline. - Or use an inline reference
[^1]
to refer to a longer footnote elseweher in the document[^1]: This is a long footnote.
.