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

Artikel i vetenskaplig tidskrift
Författare Elin Engdahl
Rasmus Gustavsson
Jesse Huang
Martin Biström
Izaura Lima Bomfim
Pernilla Stridh
Mohsen Khadeimi
Nicole Brenner
Julia Butt
Angelica Michel
Daniel Jons
Maria Hortlund
Lucia Alonso-Magdalena
Anna Karin Hedström
Louis Flamand
Masaru Ihira
Tetsushi Yoshikawa
Oluf Andersen
Jan Hillert
Lars Alfredsson
Tim Waterboer
Peter Sundström
Tomas Olsson
Ingrid Kockum
Anna Fogdell-Hahn
Publicerad i Frontiers in Immunology
Volym 10
Nummer/häfte November
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap
Språk en
Länkar https://doi.org/10.3389/fimmu.2019....
Ämnesord human herpesvirus 6A, human herpesvirus 6B, multiple sclerosis, association, risk, Epstein-Barr virus, human leukocyte antigen, serology
Ämneskategorier Klinisk medicin

Sammanfattning

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.

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