Cross-reactivity of anti-PLA2R1 autoantibodies to rabbit and mouse PLA2R1 antigens and development of two novel ELISAs with different diagnostic performances in idiopathic membranous nephropathy.
About 70% of patients with idiopathic membranous nephropathy (iMN) have autoantibodies to the phospholipase A2 receptor PLA2R1. We screened sera from iMN patients for their cross-reactivity to human (h), rabbit (rb) and mouse (m) PLA2R1 by western blot (WB) and antigen-specific ELISAs. All iMN patients recognized hPLA2R1 and rbPLA2R1 by WB, and a rbPLA2R1 ELISA was as sensitive as the standardized hPLA2R1 ELISA to monitor anti-PLA2R1 in patients with active disease or in drug-induced remission. In contrast, only 51% of patients were reactive to mPLA2R1 by WB, and a maximum of 78% were weakly to highly positive in the mPLA2R1 ELISA, suggesting that iMN patients exhibit different subsets of anti-PLA2R1 autoantibodies against epitopes that are shared or not among PLA2R1 orthologs. In a cohort of 41 patients with a mean follow-up of 42 months from anti-PLA2R1 assay, the detection of anti-mPLA2R1 autoantibodies was an independent predictor of clinical outcome in multivariate analysis (p = 0.009), and a ROC curve analysis identified a threshold of 605 RU/mL above which 100% of patients (12 patients) had a poor renal outcome (p < 0.001). A similar threshold could not be defined in hPLA2R1 and rbPLA2R1 ELISAs. We conclude that rbPLA2R1 is an alternative antigen to hPLA2R1 to measure anti-PLA2R1 in active disease while mPLA2R1 is a unique antigen that can detect a subset of anti-PLA2R1 autoantibodies present at high levels (>605 RU/mL) only in iMN patients at risk of poor prognosis, and is thus useful to predict iMN outcome.
['Seitz-Polski|Barbara|B|', 'Dolla|Guillaume|G|', 'Payré|Christine|C|', 'Tomas|Nicola M|NM|', 'Lochouarn|Marine|M|', 'Jeammet|Louise|L|', 'Mariat|Christophe|C|', 'Krummel|Thierry|T|', 'Burtey|Stéphane|S|', 'Courivaud|Cécile|C|', 'Schlumberger|Wolfgang|W|', 'Zorzi|Kévin|K|', 'Benzaken|Sylvia|S|', 'Bernard|Ghislaine|G|', 'Esnault|Vincent L M|VL|', 'Lambeau|Gérard|G|']
D000818:Animals D001323:Autoantibodies D001324:Autoantigens D015153:Blotting, Western D003429:Cross Reactions D004797:Enzyme-Linked Immunosorbent Assay D015433:Glomerulonephritis, Membranous D006801:Humans D011817:Rabbits D054507:Receptors, Phospholipase A2
Mouse PLA2R1 ELISA Membranous nephropathy Orthologs Autoimmunity Conformational epitope PLA2R1 autoantibodies Rabbit PLA2R1