Primary
membranous nephropathy (MN) is an autoimmune glomerular disease in which
autoantibodies are directed against podocyte
proteins. In about 80% of cases the main targeted
antigen is the
phospholipase A2 receptor 1 (PLA2R1). Anti-PLA2R1
antibodies are mainly
immunoglobulin G type 4 (
IgG4). However, the antigenic target remains to be defined in 20% of cases. MN can be associated with chronic inflammatory demyelinating
polyneuropathy, an
autoimmune disease of the peripheral nervous system where a common antigenic target has yet to be identified. To ascertain a possible novel target
antigen, we analyzed kidney biopsies from five patients positive for anti-
contactin 1 antibodies and presenting with MN combined with chronic inflammatory demyelinating
polyneuropathy. Eluted
IgG from biopsy sections against
contactin 1 and nerve tissue were screened. Western blot revealed
contactin 1 expression in normal kidney glomeruli. Confocal microscopic analysis showed the presence and colocalization of
contactin 1 and
IgG4 on the glomerular basement membrane of these patients. Glomerular
contactin 1 was absent in patients with anti-PLA2R1-associated MN or membranous
lupus nephritis or a healthy control. The eluted
IgG from contactin 1-positive biopsy sections but not the
IgG eluted from patients with PLA2R1 MN bound
contactin 1 with the main eluted subclass
IgG4. Eluted
IgG could bind paranodal tissue (myelinated axon) and colocalized with commercial anti-
contactin 1 antibody. Thus,
contactin 1 is a novel common antigenic target in MN associated with chronic inflammatory demyelinating
polyneuropathy. However, the precise pathophysiology remains to be elucidated.