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

Laura Martinez-Martinez, Ma Cinta Lleixà, Gemma Boera-Carnicero, Andrea Cortese, Jérôme Devaux, Ana Siles, Yusuf Rajabally, Alicia Martinez-Piñeiro, Alejandra Carvajal, Julio Pardo, Emilien Delmont, Shahram Attarian, Jordi Diaz-Manera, Ilaria Callegari, Enrico Marchioni, Diego Franciotta, Luana Benedetti, Guiseppe Lauria, Oscar de la Calle Martin, Cándido JuárezIsabel Illa, Luis Querol

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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.

Original languageEnglish
Pages (from-to)224
JournalJournal of Neuroinflammation
Volume14
Issue number1
DOIs
Publication statusPublished - Nov 16 2017

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Martinez-Martinez, L., Lleixà, M. C., Boera-Carnicero, G., Cortese, A., Devaux, J., Siles, A., Rajabally, Y., Martinez-Piñeiro, A., Carvajal, A., Pardo, J., Delmont, E., Attarian, S., Diaz-Manera, J., Callegari, I., Marchioni, E., Franciotta, D., Benedetti, L., Lauria, G., de la Calle Martin, O., ... Querol, L. (2017). Anti-NF155 chronic inflammatory demyelinating polyradiculoneuropathy strongly associates to HLA-DRB15. Journal of Neuroinflammation, 14(1), 224. https://doi.org/10.1186/s12974-017-0996-1