Screening for autoantibody targets in post-vaccination narcolepsy using proteome arrays

Research output: Contribution to journalArticle

Standard

Screening for autoantibody targets in post-vaccination narcolepsy using proteome arrays. / Lind, Alexander; Eriksson, Daniel; Akel, Omar; Ramelius, Anita; Palm, Lars; Lernmark, Åke; Kämpe, Olle; Elding Larsson, Helena; Landegren, Nils.

In: Scandinavian Journal of Immunology, Vol. 91, No. 4, e12864, 04.2020.

Research output: Contribution to journalArticle

Harvard

APA

CBE

MLA

Vancouver

Author

Lind, Alexander ; Eriksson, Daniel ; Akel, Omar ; Ramelius, Anita ; Palm, Lars ; Lernmark, Åke ; Kämpe, Olle ; Elding Larsson, Helena ; Landegren, Nils. / Screening for autoantibody targets in post-vaccination narcolepsy using proteome arrays. In: Scandinavian Journal of Immunology. 2020 ; Vol. 91, No. 4.

RIS

TY - JOUR

T1 - Screening for autoantibody targets in post-vaccination narcolepsy using proteome arrays

AU - Lind, Alexander

AU - Eriksson, Daniel

AU - Akel, Omar

AU - Ramelius, Anita

AU - Palm, Lars

AU - Lernmark, Åke

AU - Kämpe, Olle

AU - Elding Larsson, Helena

AU - Landegren, Nils

N1 - © 2020 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.

PY - 2020/4

Y1 - 2020/4

N2 - Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a specific loss of hypocretin-producing neurons. The incidence of NT1 increased in Sweden, Finland and Norway following Pandemrix®-vaccination, initiated to prevent the 2009 influenza pandemic. The pathogenesis of NT1 is poorly understood, and causal links to vaccination are yet to be clarified. The strong association with Human leukocyte antigen (HLA) DQB1*06:02 suggests an autoimmune pathogenesis, but proposed autoantigens remain controversial. We used a two-step approach to identify autoantigens in patients that acquired NT1 after Pandemrix®-vaccination. Using arrays of more than 9000 full-length human proteins, we screened the sera of 10 patients and 24 healthy subjects for autoantibodies. Identified candidate antigens were expressed in vitro to enable validation studies with radiobinding assays (RBA). The validation cohort included NT1 patients (n = 39), their first-degree relatives (FDR) (n = 66), population controls (n = 188), and disease controls representing multiple sclerosis (n = 100) and FDR to type 1 diabetes patients (n = 41). Reactivity towards previously suggested NT1 autoantigen candidates including Tribbles homolog 2, Prostaglandin D2 receptor, Hypocretin receptor 2 and α-MSH/proopiomelanocortin was not replicated in the protein array screen. By comparing case to control signals, three novel candidate autoantigens were identified in the protein array screen; LOC401464, PARP3 and FAM63B. However, the RBA did not confirm elevated reactivity towards either of these proteins. In summary, three putative autoantigens in NT1 were identified by protein array screening. Autoantibodies against these candidates could not be verified with independent methods. Further studies are warranted to identify hypothetical autoantigens related to the pathogenesis of Pandemrix®-induced NT1.

AB - Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a specific loss of hypocretin-producing neurons. The incidence of NT1 increased in Sweden, Finland and Norway following Pandemrix®-vaccination, initiated to prevent the 2009 influenza pandemic. The pathogenesis of NT1 is poorly understood, and causal links to vaccination are yet to be clarified. The strong association with Human leukocyte antigen (HLA) DQB1*06:02 suggests an autoimmune pathogenesis, but proposed autoantigens remain controversial. We used a two-step approach to identify autoantigens in patients that acquired NT1 after Pandemrix®-vaccination. Using arrays of more than 9000 full-length human proteins, we screened the sera of 10 patients and 24 healthy subjects for autoantibodies. Identified candidate antigens were expressed in vitro to enable validation studies with radiobinding assays (RBA). The validation cohort included NT1 patients (n = 39), their first-degree relatives (FDR) (n = 66), population controls (n = 188), and disease controls representing multiple sclerosis (n = 100) and FDR to type 1 diabetes patients (n = 41). Reactivity towards previously suggested NT1 autoantigen candidates including Tribbles homolog 2, Prostaglandin D2 receptor, Hypocretin receptor 2 and α-MSH/proopiomelanocortin was not replicated in the protein array screen. By comparing case to control signals, three novel candidate autoantigens were identified in the protein array screen; LOC401464, PARP3 and FAM63B. However, the RBA did not confirm elevated reactivity towards either of these proteins. In summary, three putative autoantigens in NT1 were identified by protein array screening. Autoantibodies against these candidates could not be verified with independent methods. Further studies are warranted to identify hypothetical autoantigens related to the pathogenesis of Pandemrix®-induced NT1.

UR - https://scopus.com/record/display.uri?eid=2-s2.0-85079720992&origin=inward&txGid

U2 - 10.1111/sji.12864

DO - 10.1111/sji.12864

M3 - Article

C2 - 32056243

VL - 91

JO - Scandinavian Journal of Immunology

JF - Scandinavian Journal of Immunology

SN - 0300-9475

IS - 4

M1 - e12864

ER -