Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis, 2019, Engdahl et al

Andy

Retired committee member
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.
Open access, https://www.frontiersin.org/articles/10.3389/fimmu.2019.02715/full

Press release, https://eurekalert.org/pub_releases/2019-11/ki-mlt112519.php
Researchers at Karolinska Institutet have developed a new method to separate between two different types of a common herpes virus (HHV-6) that has been linked to multiple sclerosis. By analyzing antibodies in the blood against the most divergent proteins of herpesvirus 6A and 6B, the researchers were able to show that MS-patients carry the herpesvirus 6A to a greater extent than healthy individuals. The findings, published in Frontiers in Immunology, point to a role for HHV-6A in the development of MS.
 
MS: Common herpesvirus variant raises risk

New research distinguishes between two similar variants of the human herpesvirus 6 and finds that one variant significantly increases the risk of developing multiple sclerosis (MS).

MS is an autoimmune condition that affects around 400,000Trusted Source people in the United States and 2.5 million people worldwide.

The condition affects the central nervous system, "tricking" the immune system into attacking the protective myelin sheath that surrounds the nerve cells.

The medical community has not yet identified the cause of MS. Many health professionals believe that genetic predisposition plays a role, with environmental factors such as smoking and viral infections potentially triggering MS risk genes.

Of all the viruses that may play a role in the development of MS, the Epstein-Barr virus (EBV) — which causes mononucleosis — has received the most attention from researchers.


In addition, recent researchTrusted Source has suggested that EBV can activate risk genes for other autoimmune conditions, such as lupus.

Scientists have also associated human herpesvirus 6Trusted Source (HHV-6) with MS. However, previous studies linking HHV-6 and MS were not able to differentiate between herpesvirus 6A (HHV-6A) and herpesvirus 6B (HHV-6B).


The research concluded that participants with MS were 55% more likely to have antibodies against the HHV-6A protein than the controls.

In the pre-MS group, people with a 6A viral infection were more than twice as likely to go on to develop MS than the controls. By contrast, HHV-6B was not associated with MS.


"Both HHV-6A and 6B can infect our brain cells," she adds, "but they do it in slightly different ways. Therefore, it is now interesting to go forward and attempt to map out exactly how the viruses could affect the onset of MS."
 
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