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

J Neuroinflammation. 2017 Nov 16;14(1):224. doi: 10.1186/s12974-017-0996-1.

Abstract

Background: The 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.

Methods: Thirteen 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.

Results: DRB1*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.

Conclusions: DRB1*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.

Keywords: Antibodies; CIDP; HLA DRB1*15; NF155.

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • Case-Control Studies
  • Cell Adhesion Molecules / immunology*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Male
  • Middle Aged
  • Nerve Growth Factors / immunology*
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / genetics*
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / immunology*

Substances

  • Autoantibodies
  • Autoantigens
  • Cell Adhesion Molecules
  • HLA-DRB1 Chains
  • HLA-DRB1*15 antigen
  • NFASC protein, human
  • Nerve Growth Factors