Characteristics of Anti-Contactin1 Antibody-Associated Autoimmune Nodopathies With Concomitant Membranous Nephropathy

Abstract

BackgroundThe concurrence of anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN) has previously been reported in the literature. CIDP with autoantibodies against paranodal proteins are defined as autoimmune nodopathies (AN) in the latest research. In view of the unclear relationship between CIDP and MN, we performed a case study and literature review to investigate the clinical characteristics of anti-CNTN antibody-associated AN with MN.MethodsWe detected antibodies against NF155, NF186, CNTN1, CNTN2, CASPR1 and PLA2R in blood samples of a patient with clinically manifested MN and concomitant peripheral neuropathy via double immunofluorescence staining and conducted a quantitative measurement of anti-PLA2R IgG antibodies via enzyme-linked immunosorbent assay (ELISA). Case reports of anti-CNTN1 antibody-associated AN, anti-CNTN1 antibody-associated AN with MN, and CIDP with MN were retrieved through a literature search for a comparative analysis of clinical characteristics. The cases were grouped according to the chronological order of CIDP and MN onset for the comparison of clinical characteristics.ResultsA 57-year-old man with anti-PLA2R positive MN was admitted to the hospital due to limb numbness, weakness, and proprioceptive sensory disorder. He was diagnosed with anti-CNTN1 antibody-associated AN and recovered well after immunotherapy. Our literature search returned 22 cases of CIDP with MN that occurred before, after, or concurrently with CIDP. Good responses were achieved with early single-agent or combination immunotherapy, but eight out of the 22 patients with CIDP and concomitant MN ultimately developed different motor sequelae. Five patients had anti-CNTN1 antibody-associated AN with MN. Among these patients, males accounted for the majority of cases (male:female=4:1), the mean age at onset was late (60.2 ± 15.7 years, range 43–78 years), and 40% had acute to subacute onset. Clinical manifestations included sensory-motor neuropathy, sensory ataxia caused by proprioceptive impairment, and elevated cerebrospinal fluid protein levels.ConclusionThe age at onset of CIDP with MN was earlier than that of anti-CNTN1 antibody-associated AN. MN may occur before, after or concurrently with CIDP. The early detection and isotyping of anti-CNTN1 and anti-PLA2R antibodies and the monitoring of isotype switching may be essential for suspected CIDP patients.

CIDP/autoimmune nodopathies with nephropathy: a case series study

“…Several previous reports have described the association of CIDP with nephropathy. [6][7][8][15][16][17][18][19][20][21][22][25][26][27][28][29][30][31][32][33] In recent years, a variety of autoantibodies directing against the nodes/paranodes, including neurofascin 155 (NF155), contactin-1 (CNTN1), contactin-associated protein 1 (Caspr1), and neurofascin 186 (NF186) have been identified. Atay Vural et al 11 defined seropositive CIDP as patients with antibodies against neurofascin, CNTN1 and Caspr1 and suggested these subgroups of patients had unique characteristics that distinguished them from patients with seronegative CIDP.…”

“…The new diagnostic criteria defined seropositive CIDP as the autoimmune nodopathies, not regarded as the CIDP variants, 23 though in the previous literature, considered as the special subtypes of CIDP. Interestingly, thirteen of the patients with co-morbid CIDP and membranous nephropathy were consistently found to be positive to anti-CNTN1 antibodies, [15][16][17][18][19][20][21][22]33 while two cases with anti-NF186 antibodies were reported to present with acute-onset CIDP and focal segmental glomerulosclerosis (FSGS). 34 So pathological types of nephrotic syndrome might vary depending on the types of nodal/paranodal antibodies.…”

Effect of low-dose rituximab treatment on autoimmune nodopathy with anti-contactin 1 antibody

“…Specifically, 2 patients shortly died after the first rituximab injection ( 5 , 35 ). Another 3 patients treated with rituximab of 650mg once, 375 mg/m 2 weekly for 4 consecutive weeks and of 375 mg/m 2 twice respectively showed remission of nephrotic syndrome ( 40 – 42 ). Standard-dose of rituximab was recommended in membranous nephropathy and only 60–70% of patients could reach persistent clinical remission ( 43 ), the same protocol has been used to treat immune related peripheral neuropathy.…”

Case report: Immunoadsorption therapy for anti-caspr1 antibody-associated nodopathy

“…The first-line treatments for CIDP are corticosteroids, IVIG, and PE, while RTX is recommended in seropositive CIDP patients, especially those with paranodal antibodies ( 11 , 12 ). Poor response to IVIG in nodopathy patients was observed in a prospective clinical trial, and was explained by the lack of complement fixation capacity of IgG4 subtype antibodies ( 27 ). In our case, the patient was resistant to steroids and allergic to RTX, but exhibited a prominent response to IA therapy.…”