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Autoantibody targets in vaccine-associated narcolepsy

Häggmark-Månberg, Anna; Zandian, Arash; Forsström, Björn; Khademi, Mohsen; Lima Bomfim, Izaura; Hellström, Cecilia; Arnheim-Dahlström, Lisen; Hallböök, Tove LU ; Darin, Niklas and Lundberg, Ingrid E., et al. (2016) In Autoimmunity
Abstract

Narcolepsy is a chronic sleep disorder with a yet unknown cause, but the specific loss of hypocretin-producing neurons together with a strong human leukocyte antigen (HLA) association has led to the hypothesis that autoimmune mechanisms might be involved. Here, we describe an extensive effort to profile autoimmunity repertoires in serum with the aim to find disease-related autoantigens. Initially, 57 serum samples from vaccine-associated and sporadic narcolepsy patients and controls were screened for IgG reactivity towards 10 846 fragments of human proteins using planar microarrays. The discovered differential reactivities were verified on suspension bead arrays in the same sample collection followed by further investigation of 14... (More)

Narcolepsy is a chronic sleep disorder with a yet unknown cause, but the specific loss of hypocretin-producing neurons together with a strong human leukocyte antigen (HLA) association has led to the hypothesis that autoimmune mechanisms might be involved. Here, we describe an extensive effort to profile autoimmunity repertoires in serum with the aim to find disease-related autoantigens. Initially, 57 serum samples from vaccine-associated and sporadic narcolepsy patients and controls were screened for IgG reactivity towards 10 846 fragments of human proteins using planar microarrays. The discovered differential reactivities were verified on suspension bead arrays in the same sample collection followed by further investigation of 14 antigens in 176 independent samples, including 57 narcolepsy patients. Among these 14 antigens, methyltransferase-like 22 (METTL22) and 5'-nucleotidase cytosolic IA (NT5C1A) were recognized at a higher frequency in narcolepsy patients of both sample sets. Upon sequence analysis of the 14 proteins, polymerase family, member 3 (PARP3), acyl-CoA-binding domain containing 7 (ARID4B), glutaminase 2 (GLS2) and cyclin-dependent kinase-like 1 (CDKL1) were found to contain amino acid sequences with homology to proteins found in the H1N1 vaccine. These findings could become useful elements of further clinical assays that aim towards a better phenotypic understanding of narcolepsy and its triggers.

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Contribution to journal
publication status
epub
subject
keywords
autoantibody, Narcolepsy, protein microarray, serum, vaccine-associated
in
Autoimmunity
pages
13 pages
publisher
Taylor & Francis
external identifiers
  • Scopus:84969988196
ISSN
0891-6934
DOI
10.1080/08916934.2016.1183655
language
English
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yes
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097f71cd-08ca-43cd-8385-7cf8f9a4e08a
date added to LUP
2016-06-17 17:17:53
date last changed
2016-11-14 09:42:54
@misc{097f71cd-08ca-43cd-8385-7cf8f9a4e08a,
  abstract     = {<p>Narcolepsy is a chronic sleep disorder with a yet unknown cause, but the specific loss of hypocretin-producing neurons together with a strong human leukocyte antigen (HLA) association has led to the hypothesis that autoimmune mechanisms might be involved. Here, we describe an extensive effort to profile autoimmunity repertoires in serum with the aim to find disease-related autoantigens. Initially, 57 serum samples from vaccine-associated and sporadic narcolepsy patients and controls were screened for IgG reactivity towards 10 846 fragments of human proteins using planar microarrays. The discovered differential reactivities were verified on suspension bead arrays in the same sample collection followed by further investigation of 14 antigens in 176 independent samples, including 57 narcolepsy patients. Among these 14 antigens, methyltransferase-like 22 (METTL22) and 5'-nucleotidase cytosolic IA (NT5C1A) were recognized at a higher frequency in narcolepsy patients of both sample sets. Upon sequence analysis of the 14 proteins, polymerase family, member 3 (PARP3), acyl-CoA-binding domain containing 7 (ARID4B), glutaminase 2 (GLS2) and cyclin-dependent kinase-like 1 (CDKL1) were found to contain amino acid sequences with homology to proteins found in the H1N1 vaccine. These findings could become useful elements of further clinical assays that aim towards a better phenotypic understanding of narcolepsy and its triggers.</p>},
  author       = {Häggmark-Månberg, Anna and Zandian, Arash and Forsström, Björn and Khademi, Mohsen and Lima Bomfim, Izaura and Hellström, Cecilia and Arnheim-Dahlström, Lisen and Hallböök, Tove and Darin, Niklas and Lundberg, Ingrid E. and Uhlén, Mathias and Partinen, Markku and Schwenk, Jochen M. and Olsson, Tomas and Nilsson, Peter},
  issn         = {0891-6934},
  keyword      = {autoantibody,Narcolepsy,protein microarray,serum,vaccine-associated},
  language     = {eng},
  month        = {05},
  pages        = {13},
  publisher    = {ARRAY(0x9eff200)},
  series       = {Autoimmunity},
  title        = {Autoantibody targets in vaccine-associated narcolepsy},
  url          = {http://dx.doi.org/10.1080/08916934.2016.1183655},
  year         = {2016},
}