HLA-A∗02, gender and tobacco smoking, but not multiple sclerosis, affects the IgG antibody response against human herpesvirus 6

Engdahl, Elin; Gustafsson, Rasmus; Ramanujam, Ryan; Sundqvist, Emilie; Olsson, Tomas; Hillert, Jan; Alfredsson, Lars; Kockum, Ingrid; Fogdell‐Hahn, Anna

doi:10.1016/j.humimm.2014.03.001

Cited by 6 publications

(9 citation statements)

References 195 publications

(226 reference statements)

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“…In the present study we could confirm some of our previously data using the HHV-6B lysate based commercial ELISA, namely lower serological response against HHV-6B lysate (32) and the 101K protein in males and in HLA-A*02 carriers. Female sex has been associated with increased acquisition of HHV-6B in children (5), and it is possible that the HHV-6B lysate IgG (32) and 101K IgG responses reflect this difference in primary HHV-6B infection. The association with HLA-A*02, found in our previous study (32) and suggestively confirmed for anti-101K IgG response in the present study, indicates a role for CD8+ T cells in the immune response against HHV-6B.…”

Section: Discussionsupporting

confidence: 91%

“…As smoking has been reported to be a risk factor for MS disease (44) and has been associated with higher HHV-6 IgG levels (32), the effect of smoking on HHV-6 protein-specific IgG responses was investigated. Persons with MS and with a history of regular smoking showed higher IE1A IgG levels compared to those who never smoked (p = 2×10 −5 ).…”

Section: Resultsmentioning

confidence: 99%

“…Female sex has been associated with increased acquisition of HHV-6B in children (5), and it is possible that the HHV-6B lysate IgG (32) and 101K IgG responses reflect this difference in primary HHV-6B infection. The association with HLA-A*02, found in our previous study (32) and suggestively confirmed for anti-101K IgG response in the present study, indicates a role for CD8+ T cells in the immune response against HHV-6B. In line with this notion, 101K peptides have been shown to be presented by HLA-A*02:01 on HHV-6B infected cells and these cells are recognized and killed by CD8+ T cells (59).…”

Section: Discussionmentioning

confidence: 99%

“…In line with this notion, 101K peptides have been shown to be presented by HLA-A*02:01 on HHV-6B infected cells and these cells are recognized and killed by CD8+ T cells (59). One can hypothesize that if infected cells are removed, the systemic viral burden may decrease, thus possibly explaining the lower levels of anti-HHV-6A/6B (32) and anti-101K IgG levels in individuals with the HLA-A*02 allele.…”

Section: Discussionmentioning

confidence: 99%

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Increased serological response against human herpesvirus 6A is associated with risk for multiple sclerosis

Engdahl

Gustafsson

Huang

et al. 2019

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32Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology 33 has remained controversial mainly due to the lack of serological methods that can distinguish 34 the two viruses. 35A novel multiplex serological assay measuring IgG reactivity against the immediate-early 36 protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8742 persons 37 with MS and 7215 matched controls), and a pre-MS cohort (478 individuals and 476 matched 38 controls) to investigate this further. 39The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9x10 -22 ), 40and increased risk of future MS (OR = 2.22, p = 2x10 -5 ). An interaction was observed 41 between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable 42 proportion = 0.24, p = 6x10 -6 ). In contrast, the IgG response against IE1B was negatively 43 associated with MS (OR = 0.74, p = 6x10 -11 ). The association did not differ between MS 44 subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody 45 responses were located to the Human Leukocyte Antigen (HLA) region and the strongest 46 association for IE1A was the DRB1In conclusion a role for HHV-6A in MS etiology is supported by an increased serological 49 response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA 50 genes. 51 52 53 54 55 herpesvirus 6 according to site and variant: possible greater neurotropism of variant A. Clin 595 Infect Dis (1998) 26(1):132-7. PubMed PMID: 9455521.596 3. Dewhurst S, McIntyre K, Schnabel K, Hall CB. Human herpesvirus 6 (HHV-6) variant B accounts 597 for the majority of symptomatic primary HHV-6 infections in a population of U.S. infants. J Clin 598 Microbiol (1993) 31(2):416-8. PubMed PMID: 8381815; PubMed Central PMCID: 599 PMCPMC262777.600 4. Hall CB, Long CE, Schnabel KC, Caserta MT, McIntyre KM, Costanzo MA, et al. Human 601 herpesvirus-6 infection in children. A prospective study of complications and reactivation. N Engl

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Section: Discussionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Increased serological response against human herpesvirus 6A is associated with risk for multiple sclerosis

Engdahl

Gustafsson

Huang

et al. 2019

Preprint

Self Cite

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show abstract

“…Seroconversion against HHV-6 usually occurs in early childhood (23)(24)(25) but as the two viruses have similar proteomes, it has been difficult to distinguish anti-HHV-6A from anti-HHV-6B antibody responses. This inability is a major concern when investigating virus-specific disease associations and a possible explanation for the contradictory associations between HHV-6 IgG response and MS (26)(27)(28)(29)(30)(31)(32)(33). However, even though HHV-6A and HHV-6B are 90% homologous, there are parts of their genome with more divergence (34,35).…”

Section: Introductionmentioning

confidence: 99%