OPEN IN READ APP
JOURNAL ARTICLE

Clinical Relevance of Domain-Specific Phospholipase A 2 Receptor 1 Antibody Levels in Patients with Membranous Nephropathy

Linda Reinhard, Gunther Zahner, Stephan Menzel, Friedrich Koch-Nolte, Rolf A K Stahl, Elion Hoxha
Journal of the American Society of Nephrology: JASN 2020, 31 (1): 197-207
31843985

BACKGROUND: Antibodies against phospholipase A2 receptor 1 (PLA2 R1) are found in 80% of patients with membranous nephropathy, and previous studies described three autoantibody-targeted PLA2 R1 epitope regions. Although anti-PLA2 R1 antibody levels are closely associated with treatment response and disease prognosis, the clinical role of epitope regions targeted by autoantibodies is unclear.

METHODS: In a prospective cohort of 150 patients with newly diagnosed PLA2 R1-associated membranous nephropathy, we investigated the clinical role of epitope-recognition patterns and domain-specific PLA2 R1 antibody levels by western blot and ELISA.

RESULTS: We identified a fourth epitope region in the CTLD8 domain of PLA2 R1, which was recognized by anti-PLA2 R1 antibodies in 24 (16.0%) patients. In all study patients, anti-PLA2 R1 antibodies bound both the N-terminal (CysR-FnII-CTLD1) region and the C-terminal (CTLD7-CTLD8) region of PLA2 R1 at study enrollment. The total anti-PLA2 R1 antibody levels of patients determined detection of domain-specific PLA2 R1 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 PLA2 R1 antibody levels targeting CysR, CTLD1, and CTLD7 strongly correlate with the total anti-PLA2 R1 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-PLA2 R1 antibody levels.

CONCLUSIONS: All patients with PLA2 R1-associated membranous nephropathy recognize at least two epitope regions in the N- and C-terminals of PLA2 R1 at diagnosis, contradicting the hypothesis that PLA2 R1 "epitope spreading" determines the prognosis of membranous nephropathy. Total anti-PLA2 R1 antibody levels, but not the epitope-recognition profiles at the time of diagnosis, are relevant for the clinical outcome of patients with this disease.

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
31843985
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"