Table 1.

Target antigens and biomarkers in patients with membranous nephropathy

	PLA2R1	THSD7A	EXT1/EXT2	NCAM1	NELL-1	Sema3B
UniProt ID	Q13018	Q9UPZ6	Q16394, Q93063	P13591 (120 kDa isoform)	Q92832	Q13214
Size (in amino acids)	1463	1657	746, 718	858	810	749
Compartment	Transmembrane glycoprotein	Transmembrane glycoprotein	Glycosyltransferase in Golgi and secreted	Transmembrane glycoprotein	Secreted	Secreted
Evidence for expression by podocyte	Strong	Strong	Moderate (EXT2 > EXT1)	Weak if any	Weak	Strong Sema3A ??? Sema3B
Presence in subepithelial deposits	Yes	Yes	Yes	Yes	Yes, often segmental	Yes
Circulating Ab	Yes	Yes	No	Yes	Yes	Yes, reduced Ag
Predominant subclass in deposits	IgG4	IgG4	IgG1	IgG1 +/− other subclasses	IgG1	IgG1 / not IgG4
Distinctive associations	Prototype for primary MN	Malignancy in a minority of cases	Lupus (#30%) or other systemic autoimmune disease	Lupus (#7%)	Association with malignancy (NELL-1 in tumor cells)	Pediatric MN; early onset

Adapted from Hayashi and Beck [22]. A comparison of target antigens or pathological biomarkers in subtypes of membranous nephropathy is shown. It is noticeable that the ‘new’ antigens are secreted except for NCAM, have at best a weak expression in podocytes, are associated with IgG1 deposits, and observed in different settings from PLA2R-associated membranous nephropathy. Bold characters indicate the features that differentiate the newly discovered antigen from PLA2R and THSD7A. EXT1/2, exostosins 1 and 2; MN, membranous nephropathy; NCAM1, neural cell adhesion molecule 1; NELL-1, neural epidermal growth factor-like 1 protein; Sema3B, semaphorin 3B.