Influence of MHC CLASS II in Susceptibility to Beryllium Sensitization and Chronic Beryllium Disease

Maier, Lisa A.; McGrath, Dierdre S.; Sato, Hajime; Lympany, Penny; Welsh, Ken I.; Bois, Roland du; Silveira, Lori; Fontenot, Andrew P.; Sawyer, Richard T.; Wilcox, E. M.; Newman, Lee S.

doi:10.4049/jimmunol.171.12.6910

Cited by 120 publications

(153 citation statements)

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“…Genomic DNA from the sarcoidosis and CBD cases and controls was isolated from PBMC as previously described (2,4). PCR conditions previously described (23) were used to determine genotypes and haplotypes for two promoter polymorphisms, Ϫ509 C/T (rs1800469) and Ϫ800 G/A (rs1800468), and for three codons, 10 T/C (rs1982073), 25 G/C (rs1800471), and 263 C/T (rs1800472).…”

Section: Sequence-specific Primer Pcr Determination Of Tgf-␤1 Variationmentioning

confidence: 99%

“…Individuals with CBD display granulomatous inflammation evidenced by noncaseating pulmonary granulomas and demonstrate sensitivity to beryllium based on the beryllium lymphocyte proliferation test. The sensitivity to beryllium is genetically determined, associated with an HLA class II epitope, primarily a glutamic acid at amino acid position 69 (Glu 69 ) in HLA-DPB1, and to a lesser extent a glutamic acid at amino acid position 71 in HLA-DRB1 (2). Genetic factors important in disease susceptibility and severity are not well-understood.…”

mentioning

confidence: 99%

“…Numerous studies have demonstrated that both CBD and sarcoidosis have genetic susceptibility factors (2,4,5,15). Given the important roles that TGF-␤1 plays in extracellular matrix production and immunomodulation and the clinical, pathologic, and immunologic similarities between CBD and sarcoidosis, we have hypothesized that similar genetic factors within the TGF-␤1 gene will be important in the pathogenesis of these two noninfectious granulomatous diseases.…”

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confidence: 99%

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TGF-β1 Variants in Chronic Beryllium Disease and Sarcoidosis

Jonth

Silveira

Fingerlin³

et al. 2007

The Journal of Immunology

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Evidence suggests a genetic predisposition to chronic beryllium disease (CBD) and sarcoidosis, which are clinically and pathologically similar granulomatous lung diseases. TGF-β1, a cytokine involved in mediating the fibrotic/Th1 response, has several genetic variants which might predispose individuals to these lung diseases. We examined whether certain TGF-β1 variants and haplotypes are found at higher rates in CBD and sarcoidosis cases compared with controls and are associated with disease severity indicators for both diseases. Using DNA from sarcoidosis cases/controls from A Case Control Etiologic Study of Sarcoidosis Group (ACCESS) and CBD cases/controls, TGF-β1 variants were analyzed by sequence-specific primer PCR. No significant differences were found between cases and controls for either disease in the TGF-β1 variants or haplotypes. The −509C and codon 10T were significantly associated with disease severity indicators in both CBD and sarcoidosis. Haplotypes that included the −509C and codon 10T were also associated with more severe disease, whereas one or more copies of the haplotype containing the −509T and codon 10C was protective against severe disease for both sarcoidosis and CBD. These studies suggest that the −509C and codon 10T, implicated in lower levels of TGF-β1 protein production, are shared susceptibility factors associated with more severe granulomatous disease in sarcoidosis and CBD. This association may be due to lack of down-regulation by TGF-β1, although future studies will be needed to correlate TGF-β1 protein levels with known TGF-β1 genotypes and assess whether there is a shared mechanisms for TGF-β1 in these two granulomatous diseases.

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Section: Sequence-specific Primer Pcr Determination Of Tgf-␤1 Variationmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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TGF-β1 Variants in Chronic Beryllium Disease and Sarcoidosis

Jonth

Silveira

Fingerlin³

et al. 2007

The Journal of Immunology

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“…49 Benzer olarak, HLA-DPGlu69-negatif kişilerde berilyum hipersensitivitesi ile HLA-DR*13 allellerinin ilişkili olduğu gösterilmiştir. 48 HLA-DR*13 allellerinde, DR β-zincirinin 47. pozisyonunda fenilalanin ve 71. pozisyonunda bir glutamik asit (HLA-DP 69. pozisyonundaki glutamik asitin karşılığı olan) yer almaktadır. Berilyumla indüklenen hastalıkların immunopatogenezinde bu genetik yatkınlık allellerinin rolünün hastalıkla ilgili CD4+ T hücrelerindeki Major histocompatibility complex (MHC) II molekülüne berilyum sunumu ile alakalı olduğu düşünülmektedir.…”

Section: Genetikunclassified

An industrial risk: Beryllium

Çaylak

Aytekin²

2012

J Clin Exp Invest

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Beryllium is a vocational disease factor and beryllium exposure can potentially lead to Chronic Beryllium Disease (CBD) in 2-6 % of workers. While acute lymphocytic pneumonia occurred in individuals who were exposed to high doses of beryllium, low dose exposure to beryllium followed by a long subclinical period can cause CBD characterized with chronic granulomatosis. It has been observed that varying amounts of beryllium exposure are necessary to produce symptoms of CBD or beryllium sensitization (BeS). Genetic differences between patients may be the underlying cause of these dose-effects and further study of the differences in patients exposed to beryllium may lead to earlier diagnosis and the identification of biomarkers of CBD. In this review, it is summarized the general properties of beryllium exposure, the immunopathogenesis and genetic differences of beryllium-induced diseases, genotoxicity and the carcinogenic effects of beryllium.

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“…The substitution of glutamate for lysine in this position alters the putative antigen-binding pocket, favoring beryllium binding [44]. It appears that the major effect of the polymorphism is to mediate sensitization rather than disease, with other genetic loci likely necessary for progression to overt disease [45].…”

Section: Gene-environment Interactions In Sarcoidosis Evidence For Mamentioning

confidence: 99%

Gene-environment interactions in sarcoidosis: challenge and opportunity

Culver¹,

Newman²,

Kavuru³

2007

Clinics in Dermatology

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Susceptibility to most human diseases is polygenic, with complex interactions between functional polymorphisms of single genes governing disease incidence, phenotype, or both. In this context, the contribution of any discrete gene is generally modest for a single individual, but may confer substantial attributable risk on a population level. Environmental exposure can modify the effects of a polymorphism, either by providing a necessary substrate for development of human disease or because the effects of a given exposure modulate the effects of the gene. In several diseases, genetic polymorphisms have been shown to be context-dependent, i.e. the effects of a genetic variant are realized only in the setting of a relevant exposure. Since sarcoidosis susceptibility is dependent on both genetic and environmental modifiers, the study of gene-environment interactions may yield important pathogenetic information and will likely be crucial for uncovering the range of genetic susceptibility loci. However, the complexity of these relationships implies that investigations of geneenvironment interactions will require the study of large cohorts with carefully-defined exposures and similar clinical phenotypes. A general principle is that the study of gene-environment interactions requires a sample size at least several-fold greater than for either factor alone. To date, the presence of environmental modifiers has been demonstrated for one sarcoidosis susceptibility locus, HLA-DQB1, in African-American families. This article reviews general considerations obtaining for the study of gene-environment interactions in sarcoidosis. It also describes the limited current understanding of the role of environmental influences on sarcoidosis susceptibility genes.

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Influence of MHC CLASS II in Susceptibility to Beryllium Sensitization and Chronic Beryllium Disease

Cited by 120 publications

References 44 publications

TGF-β1 Variants in Chronic Beryllium Disease and Sarcoidosis

TGF-β1 Variants in Chronic Beryllium Disease and Sarcoidosis

An industrial risk: Beryllium

Gene-environment interactions in sarcoidosis: challenge and opportunity

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