HLA class I polymorphisms are associated with development of infectious mononucleosis upon primary EBV infection

McAulay, Karen A.; Higgins, Craig; Macsween, Karen F.; Lake, Annette; Jarrett, Ruth F.; Robertson, Faye L.; Williams, Hilary; Crawford, Dorothy H.

doi:10.1172/jci32377

Cited by 96 publications

(78 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the current study, McAulay et al found that these same alleles were significantly more frequent in IM patients than in asymptomatic EBV-seropositive or EBV-seronegative individuals. The individuals with IM and possessing these associated HLA alleles also had lower lymphocyte but higher neutrophil counts, higher EBV loads, and milder IM symptoms than individuals not carrying these alleles (11).…”

Section: Genetic Predisposition To Immentioning

confidence: 93%

“…In this issue of the JCI, McAulay and colleagues examine the relationship between natural variation in genetic markers in the HLA class I locus, which influences many aspects of the immune response, and the frequency of IM (11). Previous reports had demonstrated an association between certain HLA class I alleles and EBV-positive HL (12,13).…”

Section: Genetic Predisposition To Immentioning

confidence: 99%

See 1 more Smart Citation

Role for HLA in susceptibility to infectious mononucleosis

Farrell

2007

J. Clin. Invest.

View full text Add to dashboard Cite

Factors involved in determining whether infectious mononucleosis occurs after primary EBV infection may include age, dose of virus received, and various genetic markers. A study by McAulay and colleagues reported in this issue of the JCI shows that the presence of certain HLA class I alleles correlates with the incidence and severity of infectious mononucleosis (see the related article beginning on page 3042). These same HLA alleles are also risk factors for EBV-associated Hodgkin lymphoma (HL), supporting recent epidemiology that indicates that a history of infectious mononucleosis predisposes to HL. Recent studies suggest that an EBV vaccine might help to prevent infectious mononucleosis, and further development of this should now be considered.Nonstandard abbreviations used: EBNA, EpsteinBarr nuclear antigen; HL, Hodgkin lymphoma; IM, infectious mononucleosis; LMP, latent viral protein. Conflict of interest:The author has declared that no conflict of interest exists.

show abstract

Section: Genetic Predisposition To Immentioning

confidence: 93%

Section: Genetic Predisposition To Immentioning

confidence: 99%

Role for HLA in susceptibility to infectious mononucleosis

Farrell

2007

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Microsatellite markers in or near the HLA-A locus have been associated with a higher risk of IM after primary EBV infection. 28 HLA-A*02 is also associated with a lower risk for EBV-related Hodgkin lymphoma, while A*01 is associated with an increased risk for Hodgkin lymphoma. Analysis of the four-digit level HLA typing showed that the most common suballele, A*0201, was driving the protective effect.…”

Section: Epstein-barr Virus and Multiple Sclerosis Vs Hla E Sundqvistmentioning

confidence: 97%

Epstein-Barr virus and multiple sclerosis: interaction with HLA

et al. 2011

View full text Add to dashboard Cite

Epstein-Barr virus (EBV) infection, history of infectious mononucleosis (IM)and HLA-A and DRB1 have all been proposed as risk factors for multiple sclerosis (MS). Our aim was to analyse possible interactions between antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA1) or EBNA1 fragments, presence of DRB1*15 and absence of A*02. The study population includes newly diagnosed cases and matched controls. Interaction on the additive scale was calculated using attributable proportion due to interaction (AP), which is the proportion of the incidence among individuals exposed to two interacting factors that is attributable to the interaction per se. IM showed association with MS, odds ratio (OR) ¼ 1.89 (1.45-2.48% confidence interval (CI)), as did raised EBNA1 IgG OR ¼ 1.74 (1.38-2.18 95%CI). All EBNA1 fragment IgGs were associated with MS risk. However, EBNA1 fragment 385-420 IgG levels were more strongly associated to MS than total EBNA1 IgG, OR ¼ 3.60 (2.75-4.72 95%CI), and also interacted with both DRB1*15 and absence of A*02, AP 0.60 (0.45-0.76 95%CI) and AP 0.39 (0.18-0.61 95%CI), respectively. The observed interaction between HLA class I and II genotype and reactivity to EBV-related epitopes suggest that the mechanism through which HLA genes influence the risk of MS may, at least in part, involve the immune control of EBV infection.

show abstract

“…The risk increase follows an incubation period-like distribution and is of a transient nature (20,21), suggesting that events related to control of primary EBV infection have an important impact on disease risk. However, propensity to develop IM has been associated with the HLA class I polymorphisms that were originally linked with EBVrelated HL, thus raising the possibility that the association between EBV-related HL and prior IM simply reflects shared genetic susceptibility (22).…”

mentioning

confidence: 99%

HLA-A alleles and infectious mononucleosis suggest a critical role for cytotoxic T-cell response in EBV-related Hodgkin lymphoma

Hjalgrim

Rostgaard

Johnson

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

103

View full text Add to dashboard Cite

A proportion of classical Hodgkin lymphoma (HL) is believed to be causally related to infection with the ubiquitous lymphotropic EBV. The determining factors for development of EBV-related HL remain poorly understood, but likely involve immunological control of the viral infection. Accordingly, markers of the HLA class I region have been associated with risk of EBV-related HL. To study the host genetic component of EBV-related HL further, we investigated the lymphoma's association with HLA-A*01 and HLA-A*02 simultaneously in the setting of infectious mononucleosis (IM), a risk factor for EBV-related HL, in a case-series analysis including 278 EBV-related and 656 EBV-unrelated cases of HL. By logistic regression, HLA-A*01 alleles [odds ratio (OR) per allele, 2.15; 95% CI, 1.60-2.88] were associated with increased and HLA-A*02 alleles (OR per allele, 0.70; 95% CI, 0.51-0.97) with decreased risk of EBV-related HL. These allele-specific associations corresponded to nearly 10-fold variation in risk of EBVrelated HL between HLA-A*01 and HLA-A*02 homozygotes. History of IM was also associated with risk of EBV-related HL (OR, 3.40; 95% CI, 1.74-6.66). The association between history of IM and EBV-related HL was not seen in the presence of HLA-A*02 because this allele appeared to neutralize the effect of IM on EBV-related HL risk. Our findings suggest that HLA class I-restricted EBV-specific cytotoxic T-cell responses and events in the early immune response to EBV infection in IM play critical roles in the pathogenesis of EBV-related HL.case series | epidemiology

show abstract

HLA class I polymorphisms are associated with development of infectious mononucleosis upon primary EBV infection

Cited by 96 publications

References 31 publications

Role for HLA in susceptibility to infectious mononucleosis

Role for HLA in susceptibility to infectious mononucleosis

Epstein-Barr virus and multiple sclerosis: interaction with HLA

HLA-A alleles and infectious mononucleosis suggest a critical role for cytotoxic T-cell response in EBV-related Hodgkin lymphoma

Contact Info

Product

Resources

About