Thread by @Tiff_Caza

I really enjoyed the membranous nephropathy session (happy 10th birthday PLA2R) at #KidneyWk, and here were some highlights:

@LaurenceHBeckJ1 PLA2R titers fall 3-6 months before reduction in proteinuria in MN. PLA2R titers are used as a secondary endpoint for both the GEMRITUX trial and MENTOR trials #KidneyWk.

@LaurenceHBeckJ1 Treat patients with PLA2R positive MN until the ELISA is <2 or the IFA is negative (more sensitive) #KidneyWk

@LaurenceHBeckJ1 The CysR/ricin domain is the immunodominant epitope in PLA2R. High titer correlates with poorer prognosis and epitope spreading may play a role. #KidneyWk

Antigens in membranous nephropathy include PLA2R, THSD7A, EXT, and NELL1. Distinctions between "primary" and "secondary" membranous are evolving towards antigen-based identification. #KidneyWk

@kirylukk GWAS for membranous identified PLA2R with an increased odds ratio of 2.2. HLA and other loci were also identified. #KidneyWk

@kirylukk Membranous nephropathy has a highly unusual genetic architecture with high SNP heritability, and 4 GWAS loci covering around 1/3 of all disease risk. #KidneyWk

@kirylukk Permissive HLA alleles may be required for MN susceptibility. #KidneyWk

@kirylukk A polygenic risk score in MN by top effect sizes in a GWAS correlates with anti-PLA2R titers and proteinuria. #KidneyWk

Dr. Hofstra: The immune response for primary membranous nephropathy mimics an allergic response, being IgG4 dominant. IgG1 and IgG3 antibodies are instead derived from IgM-dominant immune responses (after class switching). #KidneyWk

Dr. Hofstra: The immunodominant epitopes of PLA2R are rich in S-S bonds and are in areas of conservation across species. This suggests a role for molecular mimicry. #KidneyWk

Dr. Hofstra: Complement components in MN include C3c, C5b-9, C4d, and MBL. #KidneyWk

Dr. Hofstra: Depleting complement cofactors (Factor B, Factor D) reduce proteinuria in animal models. #KidneyWk

Dr. Hofstra: Emerging therapeutic opportunities in MN: ligand based therapies, immune adsorption, chimeric autoAbs, CAR T cells, and complement inhibitors #KidneyWk

PLA2R is expressed in the lung and smoking or air pollution may be risk factors for auto reactivity. #KidneyWk

Dr. Dahan: 30% of MN patients progress to ESKD at 10 years. We need to identify patients at risk of poor outcomes. #KidneyWk

Dr. Dahan: Use immunologic remission (anti-PLA2R <2) as a surrogate for clinical remission (proteinuria < 0.5 g/d) as a surrogate for renal survival. #KidneyWk

Dr. Dahan: According to the GEMRITUX and MENTOR trials, remission rates for MN on rituximab therapy are 61-65%. #KidneyWk

Dr. Dahan: Recommendation to test anti-PLA2R in sera bimonthly. If >90% reduction in proteinuria, stop therapy. If 50-90% continue therapy, if poor response (<50%) change therapy. #KidneyWk