Clinical Relevance of Domain-Specific Phospholipase A2 Receptor 1 Antibody Levels in Patients with Membranous Nephropathy
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Clinical Relevance of Domain-Specific Phospholipase A2 Receptor 1 Antibody Levels in Patients with Membranous Nephropathy. / Reinhard, Linda; Zahner, Gunther; Menzel, Stephan; Koch-Nolte, Friedrich; Stahl, Rolf A K; Hoxha, Elion.
In: J AM SOC NEPHROL, Vol. 31, No. 1, 01.2020, p. 197-207.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Clinical Relevance of Domain-Specific Phospholipase A2 Receptor 1 Antibody Levels in Patients with Membranous Nephropathy
AU - Reinhard, Linda
AU - Zahner, Gunther
AU - Menzel, Stephan
AU - Koch-Nolte, Friedrich
AU - Stahl, Rolf A K
AU - Hoxha, Elion
N1 - Copyright © 2020 by the American Society of Nephrology.
PY - 2020/1
Y1 - 2020/1
N2 - BACKGROUND: Antibodies 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.METHODS: In 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.RESULTS: We 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.CONCLUSIONS: All 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.
AB - BACKGROUND: Antibodies 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.METHODS: In 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.RESULTS: We 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.CONCLUSIONS: All 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.
U2 - 10.1681/ASN.2019030273
DO - 10.1681/ASN.2019030273
M3 - SCORING: Journal article
C2 - 31843985
VL - 31
SP - 197
EP - 207
JO - J AM SOC NEPHROL
JF - J AM SOC NEPHROL
SN - 1046-6673
IS - 1
ER -