Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis

Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 persons with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9 × 10-22), and increased risk of future MS (OR = 2.22, p = 2 × 10-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6 × 10-6). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10-11). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB1*13:01-DQA1*01:03-DQB1*06:03 haplotype while the main association for IE1B was DRB1*13:02-DQA1*01:02-DQB1*06:04. In conclusion a role for HHV-6A in MS etiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes.

Gustafsson, RasmusKarolinska Institutet (author)
Huang, Jesse (author)
Biström, MartinUmeå universitet,Neurovetenskaper(Swepub:umu)manbim02 (author)
Lima Bomfim, Izaura (author)
Stridh, PernillaKarolinska Institutet (author)
Khademi, MohsenKarolinska Institutet (author)
Brenner, Nicole (author)
Butt, Julia (author)
Michel, Angelika (author)
Jons, Daniel,1974Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience(Swepub:gu)xjdani (author)
Hortlund, MariaKarolinska Institutet (author)
Alonso-Magdalena, Lucia (author)
Hedström, Anna KarinKarolinska Institutet (author)
Flamand, Louis (author)
Ihira, Masaru (author)
Yoshikawa, Tetsushi (author)
Andersen, Oluf,1941Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience(Swepub:gu)xandeo (author)
Hillert, JanKarolinska Institutet (author)
Alfredsson, LarsKarolinska Institutet (author)
Waterboer, Tim (author)
Sundström, PeterUmeå universitet,Neurovetenskaper(Swepub:umu)pesu0002 (author)
Olsson, TomasKarolinska Institutet (author)
Kockum, IngridKarolinska Institutet (author)
Fogdell-Hahn, AnnaKarolinska Institutet (author)
Karolinska InstitutetNeurovetenskaper (creator_code:org_t)

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Microbiology in ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

By the university: Umeå University; Karolinska Institutet; University of Gothenburg

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.