TY - JOUR
T1 - High-resolution mapping identifies HLA class II associations with multifocal motor neuropathy
AU - Bos, Jeroen W.
AU - Otten, Henny G.
AU - Herraets, Ingrid J.T.
AU - Goedee, H. Stephan
AU - Cats, E. A.
AU - de Hoop, Talitha
AU - Verduijn, Willem
AU - van der Pol, W. Ludo
AU - van den Berg, Leonard H.
N1 - Funding Information:
Jeroen W. Bos – reports no disclosures. Henny G. Otten – reports no disclosures. Ingrid J.T. Herraets – reports no disclosures. H. Stephan Goedee – receives research support from the Prinses Beatrix Spierfonds, and received a travel grant and speaker fee from Takeda. Elies Cats – reports no disclosures. Talitha de Hoop – reports no disclosures. Willem Verduijn – reports no disclosures. W. Ludo van der Pol - serves on scientific advisory board for SAB SMA Europe, was a member of the Branaplam data monitoring committee (DMC) for Novartis, provided ad hoc consultancy for Biogen and Avexis and receives research support from the Prinses Beatrix Spierfonds, Vriendenloterij and Stichting Spieren voor Spieren. Leonard H. van den Berg - serves on scientific advisory boards for Orion, Biogen, and Cytokinetics; received an educational grant from Takeda; serves on the editorial boards of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration and the Journal of Neurology, Neurosurgery, and Psychiatry; and receives research support from the Prinses Beatrix Spierfonds, Netherlands ALS Foundation, and The Netherlands Organization for Health Research and Development (Vici Scheme, JPND [SOPHIA, STRENGTH, ALSCare]).
Publisher Copyright:
© 2021 The Authors
PY - 2021/5
Y1 - 2021/5
N2 - Objective: To gain further insight in the immunopathology underlying multifocal motor neuropathy (MMN) by exploring the association between MMN and the human leukocyte antigen (HLA) class II DRB1, DQB1, and DQA loci in depth and by correlating associated haplotypes to detailed clinical and anti-ganglioside antibody data. Methods: We performed high-resolution HLA-class II typing for the DRB1, DQB1, and DQA1 loci in 126 well-characterized MMN patients and assessed disease associations with haplotypes. We used a cohort of 1305 random individuals as a reference for haplotype distribution in the Dutch population. Results: The DRB1*15:01-DQB1*06:02 haplotype (OR 1.6 [95% CI 1.1–2.2], p < 0.05) and the DRB1*12:01-DQB1*03:01 haplotype (OR 2.7 [95% CI 1.2–5.5], p < 0.05) were more frequent in patients with MMN than in controls. These haplotypes were not associated with disease course, response to treatment or anti-ganglioside antibodies. Conclusions: MMN is associated with the DRB1*15:01-DQB1*06:02 and DRB1*12:01-DQB1*03:01 haplotypes. These HLA molecules or gene variants in their immediate vicinity may promote the specific inflammatory processes underlying MMN.
AB - Objective: To gain further insight in the immunopathology underlying multifocal motor neuropathy (MMN) by exploring the association between MMN and the human leukocyte antigen (HLA) class II DRB1, DQB1, and DQA loci in depth and by correlating associated haplotypes to detailed clinical and anti-ganglioside antibody data. Methods: We performed high-resolution HLA-class II typing for the DRB1, DQB1, and DQA1 loci in 126 well-characterized MMN patients and assessed disease associations with haplotypes. We used a cohort of 1305 random individuals as a reference for haplotype distribution in the Dutch population. Results: The DRB1*15:01-DQB1*06:02 haplotype (OR 1.6 [95% CI 1.1–2.2], p < 0.05) and the DRB1*12:01-DQB1*03:01 haplotype (OR 2.7 [95% CI 1.2–5.5], p < 0.05) were more frequent in patients with MMN than in controls. These haplotypes were not associated with disease course, response to treatment or anti-ganglioside antibodies. Conclusions: MMN is associated with the DRB1*15:01-DQB1*06:02 and DRB1*12:01-DQB1*03:01 haplotypes. These HLA molecules or gene variants in their immediate vicinity may promote the specific inflammatory processes underlying MMN.
KW - Anti-ganglioside antibodies
KW - Human leucocyte antigen
KW - Multifocal motor neuropathy
KW - Neuroimmunology
UR - http://www.scopus.com/inward/record.url?scp=85100775131&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2021.01.014
DO - 10.1016/j.neurobiolaging.2021.01.014
M3 - Article
C2 - 33582569
AN - SCOPUS:85100775131
SN - 0197-4580
VL - 101
SP - 79
EP - 84
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -