A Systematic Review and Meta-Analysis of Autoantibodies for Diagnosis and Prognosis in Patients With Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Abstract

Objectives: To review the available evidence on sensitivity and specificity of anti-NF155 antibody detection in diagnosing a specific subset of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to calculate the frequencies of different autoantibodies to paranodal proteins.Background: Diagnosis of CIDP relies on clinical and neurophysiologic criteria and lacks useful diagnostic biomarkers. A subset of CIDP patients exhibit atypical clinical phenotypes and impaired response to conventional treatments. These patients were reported as having autoantibodies targeting paranodal protein neurofascin isoform 155 (NF155), contactin-1 (CNTN1), and contactin-associated protein-1 (CASPR1). Here, we conducted a meta-analysis to summarize evidence on the diagnostic and prognostic value of these autoantibodies, especially for anti-NF155 antibody.Methods: We searched the following electronic bibliographic databases: PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science. Eligible studies provided information to calculate the frequencies of anti-NF155 antibody and anti-CNTN1 antibody, the sensitivity and specificity of anti-NF155 antibody, and the incidence of improvement and deterioration among anti-NF155 antibody seropositive CIDP patients. Heterogeneity was assessed using Q and I2 statistics.Results: The pooled frequency of anti-NF155 autoantibody across 14 studies was 7% [95% confidence interval (CI): 0.05–0.10] with high heterogeneity; the overall pooled sensitivity and specificity of anti-NF155 antibody for the diagnosis of a specific subgroup of CIDP patients were 0.45 (95% CI: 0.29–0.63) and 0.93 (95% CI: 0.86–0.97), respectively.Conclusions: For diagnosing of a specific subset of CIDP characterized by poor response to intravenous immunoglobulin (IVIg), we found a moderate sensitivity and a high specificity. The anti-NF155 antibody test should be used as a confirmatory test rather than a screening test.Systematic Review Registration: PROSPERO, identifier: CRD42020203385 and CRD42020190789.

Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy

“…Previous case series and systematic reviews suggested that patients with anti-NF155+ AN respond poorly to IVIg or that IVIg response is less frequent than in seronegative CIDP. 3 , 30 , 31 , 33 This has been described in other IgG4-mediated diseases such as anti-muscle-specific tyrosine kinase-positive myasthenia gravis. 34 There are different hypotheses on why this happens in IgG4-mediated diseases, although none has been validated.…”

Pathophysiology of the Different Clinical Phenotypes of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

“…The standard treatment, considered an autoimmune origin of CIDP, is based on the administration of corticosteroids, immunoglobulins, plasma exchange and immunosuppressive therapy [ 6 ]. The subgroup of patients with disruption of axoglial junctions in the node/paranode region tends to show tremor, ataxia, cranial nerve involvement and poor response to intravenous immunoglobulin (IVIg) [ 19 , 51 , 52 , 53 ].…”

“…Patients without defined presence of antibodies (seronegative) CIDP respond to immunotherapy in 60–80% of cases, while as much as 80% of patients with nodal/paranodal antibodies have poor response to the therapy [ 50 , 52 ]. IVIg in seronegative CIDP patients might inhibit the complement pathway and modulate the Fc receptors on macrophages, promoting remyelination, although some data are contrary to this theory [ 54 ].…”

“…The exact mechanism of nodal and paranodal antibodies remains unclear, and probably there are some discrepancies among distinct classes [ 52 ]. The poor response to IVIg in some IgG4 positive patients (seropositive CIDP) may be due to the lack of complement-mediated inflammatory cascade and macrophage-mediated demyelination [ 55 , 56 ].…”

Rituximab Responsive Relapsing–Remitting IgG4 Anticontactin 1 Chronic Inflammatory Demyelinating Polyradiculoneuropathy Associated With Membranous Nephropathy: A Case Description and Brief Review

“…[5][6][7][8] Anticontactin (CNTN1) antibodies can be detected from 1% to 8% of CIDP and exceptionally seen in association with nephrotic syndrome. 9 To date, only 24 cases of association between CIDP and membranous nephropathy were reported. 1,3,4,10,11 We aim to describe an exceptional case of rituximab responsive relapsing-remitting anti-CNTN1 IgG4 CIDP associated with a nephrotic syndrome and to compare our observation with previously reported similar cases.…”