Contactin-1 is a novel target antigen in membranous nephropathy associated with chronic inflammatory demyelinating polyneuropathy

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. 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. When contactin antibodies hit the podocyte: a new neurorenal syndromeKidney InternationalVol. 100Issue 6PreviewMembranous nephropathy can be associated with various etiologies and antigens. In this issue of Kidney International, Le Quintrec et al. described contactin-1 cell adhesion molecule as a novel target antigen shared by the peripheral nerve and podocyte in patients with neurological disease and membranous nephropathy. Full-Text PDF In This IssueKidney InternationalVol. 100Issue 6PreviewThe over-the-counter supplement lipoic acid (LA) is thought to be an antioxidant. Spain et al. report the unexpected development of proteinuria in 3 patients with multiple sclerosis (MS) who were receiving LA in a clinical trial for MS. Two patients had kidney biopsies and were found to have a histologic pattern of membranous nephropathy (MN), and their kidney tissue stained for neural epidermal growth factor-like 1 (NELL1). Two other patients from the investigators’ nephrology clinics also developed NELL1-positive MN and were taking LA. Full-Text PDF Contactin-1–associated membranous nephropathy: complete immunologic and clinical remission with rituximabKidney InternationalVol. 100Issue 6PreviewIn this issue of Kidney International, Le Quintrec et al.1 identified contactin-1 (CNTN1) as the potential antigen in 5 patients with membranous nephropathy (MN) associated with chronic inflammatory demyelinating polyneuropathy (CIDP). Here, we report the case of an additional patient with this rare association who experienced remission of his neurologic disease and nephrotic syndrome after the addition of rituximab, after having failed therapy with i.v. Ig alone. Full-Text PDF