MSH5 is not a genetic predisposing factor for immunoglobulin A deficiency but marks the HLA-DRB1*0102 subgroup carrying susceptibility

Pozo, N. Del; Medrano, Luz María; Cénit, M C; Fernández‐Arquero, Miguel; Ferreira, Antônio Walter; García‐Rodriguez, M. C.; Concha, Emilio G. de la; Urcelay, Elena; Núñez, Concepción

doi:10.1016/j.humimm.2010.06.007

Cited by 5 publications

(4 citation statements)

References 17 publications

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“…However, Guikema et al [115] observed a large variety of splice variants of MSH5 mRNA (all of which are unlikely to be stable) and suggested that MSH5 was nonfunctional and therefore probably does not participate in Ig class switching. Recently, it has been shown that haplotypes of MSH5 are associated with IgA deficiency [116, 117] but are not likely to be the causative mutations [117]. …”

Section: The Influence Of the Mhc On Antibody Productionmentioning

confidence: 99%

The Influence of MHC and Immunoglobulins A and E on Host Resistance to Gastrointestinal Nematodes in Sheep

Lee

Munyard

Gregg

et al. 2011

Journal of Parasitology Research

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Gastrointestinal nematode parasites in farmed animals are of particular importance due to their effects on production. In Australia, it is estimated that the direct and indirect effects of parasite infestation cost the animal production industries hundreds of millions of dollars each year. The main factors considered by immunologists when studying gastrointestinal nematode infections are the effects the host's response has on the parasite, which immunological components are responsible for these effects, genetic factors involved in controlling immunological responses, and the interactions between these forming an interconnecting multilevel relationship. In this paper, we describe the roles of immunoglobulins, in particular IgA and IgE, and the major histocompatibility complex in resistance to gastrointestinal parasites in sheep. We also draw evidence from other animal models to support the involvement of these immune components. Finally, we examine how IgA and IgE exert their influence and how methods may be developed to manage susceptible animals.

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Section: The Influence Of the Mhc On Antibody Productionmentioning

confidence: 99%

The Influence of MHC and Immunoglobulins A and E on Host Resistance to Gastrointestinal Nematodes in Sheep

Lee

Munyard

Gregg

et al. 2011

Journal of Parasitology Research

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“…It is interesting to note that the 2 missense mutations that we have recently characterized in MSH5 , L85F and P786S, located in the HLA Class III region, travel specifically on this extended haplotype [32]. It should be noted, however, that this hypothesis was not supported by a recent study by Pozo et al , suggesting that recombinant (non-DRB1*0102) haplotypes carrying the L85F variant did not show evidence of association with IgAD [33]. Nevertheless, the conservation and low frequency of recombinant HLA-B*1402-DRB1*0102-DQB1*05 haplotypes in European populations, warrant further analyses and a larger sample size to confirm whether these missense mutations are the causal variants for IgAD in this haplotype.…”

Section: Discussionmentioning

confidence: 74%

High-Density SNP Mapping of the HLA Region Identifies Multiple Independent Susceptibility Loci Associated with Selective IgA Deficiency

Ferreira¹,

Pan‐Hammarström

Graham³

et al. 2012

PLoS Genet

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Selective IgA deficiency (IgAD; serum IgA<0.07 g/l) is the most common form of human primary immune deficiency, affecting approximately 1∶600 individuals in populations of Northern European ancestry. The polygenic nature of IgAD is underscored by the recent identification of several new risk genes in a genome-wide association study. Among the characterized susceptibility loci, the association with specific HLA haplotypes represents the major genetic risk factor for IgAD. Despite the robust association, the nature and location of the causal variants in the HLA region remains unknown. To better characterize the association signal in this region, we performed a high-density SNP mapping of the HLA locus and imputed the genotypes of common HLA-B, -DRB1, and -DQB1 alleles in a combined sample of 772 IgAD patients and 1,976 matched controls from 3 independent European populations. We confirmed the complex nature of the association with the HLA locus, which is the result of multiple effects spanning the entire HLA region. The primary association signal mapped to the HLA-DQB1*02 allele in the HLA Class II region (combined P = 7.69×10−57; OR = 2.80) resulting from the combined independent effects of the HLA-B*0801-DRB1*0301-DQB1*02 and -DRB1*0701-DQB1*02 haplotypes, while additional secondary signals were associated with the DRB1*0102 (combined P = 5.86×10−17; OR = 4.28) and the DRB1*1501 (combined P = 2.24×10−35; OR = 0.13) alleles. Despite the strong population-specific frequencies of HLA alleles, we found a remarkable conservation of these effects regardless of the ethnic background, which supports the use of large multi-ethnic populations to characterize shared genetic association signals in the HLA region. We also provide evidence for the location of association signals within the specific extended haplotypes, which will guide future sequencing studies aimed at characterizing the precise functional variants contributing to disease pathogenesis.

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“…Subsequently, however, Pozo et al [52] argued that the MSH5 gene is not a genetic predisposing factor for IgAD but marks the HLA-DRB1Ã0102 subgroup carrying the susceptibility gene at least in the Spanish population.…”

Section: Mhc Involvementmentioning

confidence: 99%

IgA deficiency

Wang

Hammarström

2012

Current Opinion in Allergy &Amp; Clinical Immunology

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MSH5 is not a genetic predisposing factor for immunoglobulin A deficiency but marks the HLA-DRB1*0102 subgroup carrying susceptibility

Cited by 5 publications

References 17 publications

The Influence of MHC and Immunoglobulins A and E on Host Resistance to Gastrointestinal Nematodes in Sheep

The Influence of MHC and Immunoglobulins A and E on Host Resistance to Gastrointestinal Nematodes in Sheep

High-Density SNP Mapping of the HLA Region Identifies Multiple Independent Susceptibility Loci Associated with Selective IgA Deficiency

IgA deficiency

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