Anti-NF155 chronic inflammatory demyelinating polyradiculoneuropathy strongly associates to HLA-DRB15

Abstract

BackgroundThe aim of the research is to study the human leukocyte antigen (HLA) class II allele frequencies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with anti-neurofascin 155 (NF155) antibodies.MethodsThirteen anti-NF155+ and 35 anti-NF155 negative (anti-NF155neg) CIDP patients were included in a case-control study. The frequencies of the DRB1 HLA allele were analyzed in all patients while DQ frequencies were only studied in patients sharing the DRB1*15 allele. In silico HLA-peptide binding and NF155 antigenicity, predictions were performed to analyze overlap between presented peptides and antigenic regions.ResultsDRB1*15 alleles (DRB1*15:01 and DRB1*15:02) were present in 10 out of 13 anti-NF155+ CIDP patients and in only 5 out of 35 anti-NF155neg CIDP patients (77 vs 14%; OR = 20, CI = 4.035 to 99.13). DRB1*15 alleles appeared also in significantly higher proportions in anti-NF155+ CIDP than in normal population (77 vs 17%; OR = 16.9, CI = 4.434 to 57.30). Seven anti-NF155+ CIDP patients (53%) and 5 anti-NF155neg CIDP patients had the DRB1*15:01 allele (OR = 7, p = 0.009), while 3 anti-NF155+ CIDP patients and none of the anti-NF155neg CIDP patients had the DRB1*15:02 allele (OR = 23.6, p = 0.016). In silico analysis of the NF155 peptides binding to DRB1*15 alleles showed significant overlap in the peptides presented by the 15:01 and 15:02 alleles, suggesting functional homology.ConclusionsDRB1*15 alleles are the first strong risk factor associated to a CIDP subset, providing additional evidence that anti-NF155+ CIDP patients constitute a differentiated disease within the CIDP syndrome.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-0996-1) contains supplementary material, which is available to authorized users.

Intrathecal cytokine profile in neuropathy with anti‐neurofascin 155 antibody

“…By contrast, extensive proximal nerve hypertrophy and pronounced CSF protein elevation, suggesting severe inflammation and/or edema of nerve roots, is unique to this condition, but is difficult to explain solely by IgG4 antibody functions. Recently, a strong association of certain human leukocyte antigen ( HLA ) class II alleles with NF155 + CIDP was reported in a European series, suggesting HLA class II‐restricted T‐cell involvement. These observations prompted us to clarify the CSF cytokine profile in patients with IgG4 NF155 + CIDP to elucidate the mechanism.…”

ARTHUR ASBURY LECTURE: Chronic inflammatory demyelinating polyradiculoneuropathy: clinical aspects and new animal models of auto‐immunity to nodal components

“…In a collaborative study we found that anti‐NF155+ CIDP patients associates with HLA‐DRB15 20 times more frequently than in seronegative CIDP (Martinez‐Martinez and coworkers, unpublished observation) (Martinez‐Martinez et al, ) further supporting the idea that patients with these antibodies constitute a distinct subset of CIDP.…”

Anti‐neurofascin 155 antibody‐related neuropathy

“…Very recently, European researchers reported that the DRB1*15 alleles ( DRB1*15:01 and DRB1*15:02 ) were present in 10 out of 13 anti‐NF155 antibody‐positive CIDP patients and in just five out of 35 anti‐NF155 antibody‐negative CIDP patients (77% vs 14%; odds ratio 20, 95% confidence interval 4.035–99.13) . Strong relationships between particular human leukocyte antigen class II alleles and other IgG4‐mediated autoimmune diseases have been reported, such as anti‐muscle‐specific tyrosine kinase antibody myasthenia gravis ( DR14‐DQ5 haplotype), leucine‐rich glioma inactivated 1 encephalitis ( DRB1*07:01–DQB1*02:02 haplotype) and thrombotic thrombocytopenic purpura ( DRB1*11 ), suggesting that these disorders have common pathomechanisms.…”