Skip to main content
Top
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

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

Authors: 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 Juárez, Isabel Illa, Luis Querol

Published in: Journal of Neuroinflammation | Issue 1/2017

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Querol L, Devaux J, Rojas-Garcia R, Illa I. Autoantibodies in chronic inflammatory neuropathies: diagnostic and therapeutic implications. Nat Rev Neurol. 2017;13:533–47.CrossRefPubMed Querol L, Devaux J, Rojas-Garcia R, Illa I. Autoantibodies in chronic inflammatory neuropathies: diagnostic and therapeutic implications. Nat Rev Neurol. 2017;13:533–47.CrossRefPubMed
2.
go back to reference Querol L, Nogales-Gadea G, Rojas-Garcia R, Martinez-Hernandez E, Diaz-Manera J, Suárez-Calvet X, et al. Antibodies to contactin-1 in chronic inflammatory demyelinating polyneuropathy. Ann Neurol. 2013;73:370–80.CrossRefPubMed Querol L, Nogales-Gadea G, Rojas-Garcia R, Martinez-Hernandez E, Diaz-Manera J, Suárez-Calvet X, et al. Antibodies to contactin-1 in chronic inflammatory demyelinating polyneuropathy. Ann Neurol. 2013;73:370–80.CrossRefPubMed
3.
go back to reference Querol L, Nogales-Gadea G, Rojas-Garcia R, Diaz-Manera J, Pardo J, Ortega-Moreno A, et al. Neurofascin IgG4 antibodies in CIDP associate with disabling tremor and poor response to IVIg. Neurology. 2014;82:879–86.CrossRefPubMedPubMedCentral Querol L, Nogales-Gadea G, Rojas-Garcia R, Diaz-Manera J, Pardo J, Ortega-Moreno A, et al. Neurofascin IgG4 antibodies in CIDP associate with disabling tremor and poor response to IVIg. Neurology. 2014;82:879–86.CrossRefPubMedPubMedCentral
4.
go back to reference Doppler K, Appeltshauser L, Villmann C, Martin C, Peles E, Krämer HH, et al. Auto-antibodies to contactin-associated protein 1 (Caspr) in two patients with painful inflammatory neuropathy. Brain. 2016;139:2617–30.CrossRefPubMed Doppler K, Appeltshauser L, Villmann C, Martin C, Peles E, Krämer HH, et al. Auto-antibodies to contactin-associated protein 1 (Caspr) in two patients with painful inflammatory neuropathy. Brain. 2016;139:2617–30.CrossRefPubMed
5.
go back to reference Delmont E, Manso C, Querol L, Cortese A, Berardinelli A, Lozza A, et al. Autoantibodies to nodal isoforms of neurofascin in chronic inflammatory demyelinating polyneuropathy. Brain. 2017; in press Delmont E, Manso C, Querol L, Cortese A, Berardinelli A, Lozza A, et al. Autoantibodies to nodal isoforms of neurofascin in chronic inflammatory demyelinating polyneuropathy. Brain. 2017; in press
6.
go back to reference Devaux JJ, Miura Y, Fukami Y, Inoue T, Manso C, Belghazi M, et al. Neurofascin-155 IgG4 in chronic inflammatory demyelinating polyneuropathy. Neurology. 2016;86:800–7.CrossRefPubMedPubMedCentral Devaux JJ, Miura Y, Fukami Y, Inoue T, Manso C, Belghazi M, et al. Neurofascin-155 IgG4 in chronic inflammatory demyelinating polyneuropathy. Neurology. 2016;86:800–7.CrossRefPubMedPubMedCentral
7.
go back to reference Querol L, Rojas-Garcia R, Diaz-Manera J, Barcena J, Pardo J, Ortega-Moreno A, et al. Rituximab in treatment-resistant CIDP with antibodies against paranodal proteins. Neurol Neuroimmunol Neuroinflammation. 2015;2:e149.CrossRef Querol L, Rojas-Garcia R, Diaz-Manera J, Barcena J, Pardo J, Ortega-Moreno A, et al. Rituximab in treatment-resistant CIDP with antibodies against paranodal proteins. Neurol Neuroimmunol Neuroinflammation. 2015;2:e149.CrossRef
8.
go back to reference Koike H, Kadoya M, Kaida K, Ikeda S, Kawagashira Y, Iijima M, et al. Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with antineurofascin-155 and anticontactin-1 antibodies. J Neurol Neurosurg Psychiatry. 2017; jnnp-2016-314895 Koike H, Kadoya M, Kaida K, Ikeda S, Kawagashira Y, Iijima M, et al. Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with antineurofascin-155 and anticontactin-1 antibodies. J Neurol Neurosurg Psychiatry. 2017; jnnp-2016-314895
9.
go back to reference Vallat J-M, Yuki N, Sekiguchi K, Kokubun N, Oka N, Mathis S, et al. Paranodal lesions in chronic inflammatory demyelinating polyneuropathy associated with anti-neurofascin 155 antibodies. Neuromuscul Disord Elsevier BV. 2016;27:290–3.CrossRef Vallat J-M, Yuki N, Sekiguchi K, Kokubun N, Oka N, Mathis S, et al. Paranodal lesions in chronic inflammatory demyelinating polyneuropathy associated with anti-neurofascin 155 antibodies. Neuromuscul Disord Elsevier BV. 2016;27:290–3.CrossRef
10.
go back to reference Kim T-J, Lee S-T, Moon J, Sunwoo J-S, Byun J, Lim J, et al. Anti-LGI1 encephalitis is associated with unique HLA subtypes. Ann Neurol. 2017;81:183–92.CrossRefPubMed Kim T-J, Lee S-T, Moon J, Sunwoo J-S, Byun J, Lim J, et al. Anti-LGI1 encephalitis is associated with unique HLA subtypes. Ann Neurol. 2017;81:183–92.CrossRefPubMed
11.
go back to reference Gaig C, Graus F, Compta Y, Högl B, Bataller L, Brüggemann N, et al. Clinical manifestations of the anti-IgLON5 disease. Neurology. 2017;88:1736–43.CrossRefPubMed Gaig C, Graus F, Compta Y, Högl B, Bataller L, Brüggemann N, et al. Clinical manifestations of the anti-IgLON5 disease. Neurology. 2017;88:1736–43.CrossRefPubMed
12.
go back to reference Huijbers MG, Querol LA, Niks EH, Plomp JJ, van der Maarel SM, Graus F, et al. The expanding field of IgG4-mediated neurological autoimmune disorders. Eur J Neurol. 2015;22:1151–61.CrossRefPubMed Huijbers MG, Querol LA, Niks EH, Plomp JJ, van der Maarel SM, Graus F, et al. The expanding field of IgG4-mediated neurological autoimmune disorders. Eur J Neurol. 2015;22:1151–61.CrossRefPubMed
13.
go back to reference Van den Bergh PYK, Hadden RDM, Bouche P, Cornblath DR, Hahn A, Illa I, et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripher. Eur J Neurol. 2010;17:356–63.CrossRefPubMed Van den Bergh PYK, Hadden RDM, Bouche P, Cornblath DR, Hahn A, Illa I, et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripher. Eur J Neurol. 2010;17:356–63.CrossRefPubMed
14.
go back to reference Balas A, García-Sánchez F, Vicario JL. Allelic and haplotypic HLA frequency distribution in Spanish hematopoietic patients. Implications for unrelated donor searching. Tissue Antigens. 2011;77:45–53.CrossRefPubMed Balas A, García-Sánchez F, Vicario JL. Allelic and haplotypic HLA frequency distribution in Spanish hematopoietic patients. Implications for unrelated donor searching. Tissue Antigens. 2011;77:45–53.CrossRefPubMed
15.
go back to reference Wang P, Sidney J, Kim Y, Sette A, Lund O, Nielsen M, et al. Peptide binding predictions for HLA DR, DP and DQ molecules. BMC Bioinformatics. 2010;11:568.CrossRefPubMedPubMedCentral Wang P, Sidney J, Kim Y, Sette A, Lund O, Nielsen M, et al. Peptide binding predictions for HLA DR, DP and DQ molecules. BMC Bioinformatics. 2010;11:568.CrossRefPubMedPubMedCentral
16.
go back to reference Wang P, Sidney J, Dow C, Mothé B, Sette A, Peters B. A systematic assessment of MHC class II peptide binding predictions and evaluation of a consensus approach. Stormo G, editor PLoS Comput Biol. 2008;4:e1000048. Wang P, Sidney J, Dow C, Mothé B, Sette A, Peters B. A systematic assessment of MHC class II peptide binding predictions and evaluation of a consensus approach. Stormo G, editor PLoS Comput Biol. 2008;4:e1000048.
17.
go back to reference Singh H, Raghava GP. ProPred: prediction of HLA-DR binding sites. Bioinformatics. 2001;17:1236–7.CrossRefPubMed Singh H, Raghava GP. ProPred: prediction of HLA-DR binding sites. Bioinformatics. 2001;17:1236–7.CrossRefPubMed
18.
go back to reference Kolaskar AS, Tongaonkar PC. A semi-empirical method for prediction of antigenic determinants on protein antigens. FEBS Lett. 1990;276:172–4.CrossRefPubMed Kolaskar AS, Tongaonkar PC. A semi-empirical method for prediction of antigenic determinants on protein antigens. FEBS Lett. 1990;276:172–4.CrossRefPubMed
19.
go back to reference Niks EH, Kuks JBM, Roep BO, Haasnoot GW, Verduijn W, Ballieux BEPB, et al. Strong association of MuSK antibody-positive myasthenia gravis and HLA-DR14-DQ5. Neurology. 2006;66:1772–4.CrossRefPubMed Niks EH, Kuks JBM, Roep BO, Haasnoot GW, Verduijn W, Ballieux BEPB, et al. Strong association of MuSK antibody-positive myasthenia gravis and HLA-DR14-DQ5. Neurology. 2006;66:1772–4.CrossRefPubMed
20.
go back to reference Blum S, McCombe PA. Genetics of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): current knowledge and future directions. J Peripher Nerv Syst. 2014;19:88–103.CrossRefPubMed Blum S, McCombe PA. Genetics of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): current knowledge and future directions. J Peripher Nerv Syst. 2014;19:88–103.CrossRefPubMed
21.
go back to reference Sutedja NA, Cats EA. Increased frequency of HLA-DRB1* 15 in patients with multifocal motor neuropathy. 2010; Sutedja NA, Cats EA. Increased frequency of HLA-DRB1* 15 in patients with multifocal motor neuropathy. 2010;
22.
go back to reference Doppler K, Appeltshauser L, Krämer HH, Ng JKM, Meinl E, Villmann C, et al. Contactin-1 and neurofascin-155/−186 are not targets of auto-antibodies in multifocal motor neuropathy. PLoS One. 2015;10:e0134274.CrossRefPubMedPubMedCentral Doppler K, Appeltshauser L, Krämer HH, Ng JKM, Meinl E, Villmann C, et al. Contactin-1 and neurofascin-155/−186 are not targets of auto-antibodies in multifocal motor neuropathy. PLoS One. 2015;10:e0134274.CrossRefPubMedPubMedCentral
23.
go back to reference Gourraud P-A, Harbo HF, Hauser SL, Baranzini SE. The genetics of multiple sclerosis: an up-to-date review. Immunol Rev. 2012;248:87–103.CrossRefPubMed Gourraud P-A, Harbo HF, Hauser SL, Baranzini SE. The genetics of multiple sclerosis: an up-to-date review. Immunol Rev. 2012;248:87–103.CrossRefPubMed
24.
go back to reference Mathey EK, Derfuss T, Storch MK, Williams KR, Hales K, Woolley DR, et al. Neurofascin as a novel target for autoantibody-mediated axonal injury. J Exp Med. 2007;204:2363–72.CrossRefPubMedPubMedCentral Mathey EK, Derfuss T, Storch MK, Williams KR, Hales K, Woolley DR, et al. Neurofascin as a novel target for autoantibody-mediated axonal injury. J Exp Med. 2007;204:2363–72.CrossRefPubMedPubMedCentral
25.
go back to reference Kawamura N, Yamasaki R, Yonekawa T, Matsushita T, Kusunoki S, Nagayama S, et al. Anti-neurofascin antibody in patients with combined central and peripheral demyelination. Neurology. 2013;81:714–22.CrossRefPubMed Kawamura N, Yamasaki R, Yonekawa T, Matsushita T, Kusunoki S, Nagayama S, et al. Anti-neurofascin antibody in patients with combined central and peripheral demyelination. Neurology. 2013;81:714–22.CrossRefPubMed
26.
go back to reference Cortese A, Devaux JJ, Zardini E, Manso C, Taieb G, Carra Dallière C, et al. Neurofascin-155 as a putative antigen in combined central and peripheral demyelination. Neurol Neuroimmunol Neuroinflammation. 2016;3:e238.CrossRef Cortese A, Devaux JJ, Zardini E, Manso C, Taieb G, Carra Dallière C, et al. Neurofascin-155 as a putative antigen in combined central and peripheral demyelination. Neurol Neuroimmunol Neuroinflammation. 2016;3:e238.CrossRef
27.
go back to reference Le W-B, Shi J-S, Zhang T, Liu L, Qin H-Z, Liang S, et al. HLA-DRB1*15:01 and HLA-DRB3*02:02 in PLA2R-related membranous nephropathy. J Am Soc Nephrol. 2017;28:1642–50.CrossRefPubMed Le W-B, Shi J-S, Zhang T, Liu L, Qin H-Z, Liang S, et al. HLA-DRB1*15:01 and HLA-DRB3*02:02 in PLA2R-related membranous nephropathy. J Am Soc Nephrol. 2017;28:1642–50.CrossRefPubMed
28.
go back to reference Meyer Zu Horste G, Heidenreich H, Lehmann HC, Ferrone S, Hartung H-P, Wiendl H, et al. Expression of antigen processing and presenting molecules by Schwann cells in inflammatory neuropathies. Glia. 2010;58:80–92.CrossRefPubMed Meyer Zu Horste G, Heidenreich H, Lehmann HC, Ferrone S, Hartung H-P, Wiendl H, et al. Expression of antigen processing and presenting molecules by Schwann cells in inflammatory neuropathies. Glia. 2010;58:80–92.CrossRefPubMed
Metadata
Title
Anti-NF155 chronic inflammatory demyelinating polyradiculoneuropathy strongly associates to HLA-DRB15
Authors
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 Juárez
Isabel Illa
Luis Querol
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-0996-1

Other articles of this Issue 1/2017

Journal of Neuroinflammation 1/2017 Go to the issue