Role for HLA in susceptibility to infectious mononucleosis

Farrell, Patrick J.

doi:10.1172/jci33563

Cited by 11 publications

(12 citation statements)

References 20 publications

(28 reference statements)

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“…HLA-A molecules have a central role in the immune system because they are responsible to present and recognize antigens. The study of genetic differences in the HLA locus is important since HLA class 1 alleles may affect viral peptide presentation to T cells, and consequently the effectiveness of the immune response (McAulay et al, 2007;Farrell, 2007). The HLA-A locus A > T (rs2530388) was described as associated with increased risk of infectious mononucleosis (McAulay et al, 2007), nevertheless our data showed no significant associations with NPC development and therefore our results may indicate a different result point of interest regarding possible EBV-association.…”

Section: Hla Locus Snpscontrasting

confidence: 55%

Polymorphisms in host immune response associated genes and risk of nasopharyngeal carcinoma development in Portugal

et al. 2016

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Section: Hla Locus Snpscontrasting

confidence: 55%

Polymorphisms in host immune response associated genes and risk of nasopharyngeal carcinoma development in Portugal

et al. 2016

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“…It is one of the most common viral infections of humans, with over 90% of individuals becoming infected at some time during their life [36]. As maternal antibody protection disappears after birth, infants become susceptible to infection by EBV.…”

Section: Introductionmentioning

confidence: 99%

“…EBV is a member of the herpes family of double-stranded linear DNA viruses, which is also referred to as the human herpes virus 4 (or HHV-4). It is one of the most common viral infections of humans, with over 90% of individuals becoming infected at some time during their life [36] . As maternal antibody protection disappears after birth, infants become susceptible to infection by EBV.…”

Section: Introductionmentioning

confidence: 99%

The Causal Cascade to Multiple Sclerosis: A Model for MS Pathogenesis

2009

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BackgroundMS pathogenesis seems to involve both genetic susceptibility and environmental risk factors. Three sequential factors are implicated in the environmental risk. The first acts near birth, the second acts during childhood, and the third acts long thereafter. Two candidate factors (vitamin D deficiency and Epstein-Barr viral infection) seem well suited to the first two environmental events.Methodology/Principal FindingsA mathematical Model for MS pathogenesis is developed, incorporating these environmental and genetic factors into a causal scheme that can explain some of the recent changes in MS-epidemiology (e.g., increasing disease prevalence, a changing sex-ratio, and regional variations in monozygotic twin concordance rates).Conclusions/SignificanceThis Model suggests that genetic susceptibility is overwhelmingly the most important determinant of MS pathogenesis. Indeed, over 99% of individuals seem genetically incapable of developing MS, regardless of what environmental exposures they experience. Nevertheless, the contribution of specific genes to MS-susceptibility seems only modest. Thus, despite HLA DRB1*1501 being the most consistently identified genetic marker of MS-susceptibility (being present in over 50% of northern MS patient populations), only about 1% of individuals with this allele are even genetically susceptible to getting MS. Moreover, because genetic susceptibility seems so similar throughout North America and Europe, environmental differences principally determine the regional variations in disease characteristics. Additionally, despite 75% of MS-patients being women, men are 60% more likely to be genetically-susceptible than women. Also, men develop MS at lower levels of environmental exposure than women. Nevertheless, women are more responsive to the recent changes in environmental-exposure (whatever these have been). This explains both the changing sex-ratio and the increasing disease prevalence (which has increased by a minimum of 32% in Canada over the past 35 years). As noted, environmental risk seems to result from three sequential components of environmental exposure. The potential importance of this Model for MS pathogenesis is that, if correct, a therapeutic strategy, designed to interrupt one or more of these sequential factors, has the potential to markedly reduce or eliminate disease prevalence in the future.

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“…The target cell of primary EBV infection is B cells and the symptoms of IM are a result of immune response to the EBV infection, including excessive production of inflamma-tory cytokines by T cells [25]. A genetic contribution to the variability in cytokine secretion in response to antigens has been demonstrated, this could also partially explain a heritable IM susceptibility [26].…”

Section: Discussionmentioning

confidence: 99%

Evidence of genetic susceptibility to infectious mononucleosis: a twin study

et al. 2011

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SUMMARY Infectious mononucleosis is a clinical manifestation of primary Epstein–Barr virus infection. It is unknown whether genetic factors contribute to risk. To assess heritability, we compared disease concordance in monozygotic to dizygotic twin pairs from the population-based California Twin Program and assessed the risk to initially unaffected co-twins. One member of 611 and both members of 58 twin pairs reported a history of infectious mononucleosis. Pairwise concordance in monozygotic and dizygotic pairs was respectively 12·1% [standard error (s.e.)=1·9%] and 6·1% (s.e.=1·2%). The relative risk (hazard ratio) of monozygotic compared to dizygotic unaffected co-twins of cases was 1·9 [95% confidence interval (CI) 1·1–3·4, P=0·03], over the follow-up period. When the analysis was restricted to same-sex twin pairs, that estimate was 2·5 (95% CI 1·2–5·3, P=0·02). The results are compatible with a heritable contribution to the risk of infectious mononucleosis.

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Role for HLA in susceptibility to infectious mononucleosis

Cited by 11 publications

References 20 publications

Polymorphisms in host immune response associated genes and risk of nasopharyngeal carcinoma development in Portugal

Polymorphisms in host immune response associated genes and risk of nasopharyngeal carcinoma development in Portugal

The Causal Cascade to Multiple Sclerosis: A Model for MS Pathogenesis

Evidence of genetic susceptibility to infectious mononucleosis: a twin study

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