Histocompatibility Determinants in Multiple Sclerosis

Jersild, Casper; Dupont, Bo; T, Fog; Platz, P.; Svejgaard, A.

doi:10.1111/j.1600-065x.1975.tb01556.x

Cited by 60 publications

(48 citation statements)

References 23 publications

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“…These results indicate that susceptibility to CAH is more closely associated with HL-A8 than with MLR-S 8a. This situation is clearly different from that described by Jersild et al (15,16). They identified an MLR-S allele, 7a, associated with HL-A7 and showed that patients with multiple sclerosis have a significantly higher frequency of 7a than HL-A genotype matched controls.…”

Section: Genetic Analysis Of Patients With Chronic Active Hepatitiscontrasting

confidence: 53%

Genetic analysis of patients with chronic active hepatitis.

Page¹,

Sharp²,

Greenberg³

et al. 1975

J. Clin. Invest.

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A B S T R A C T 21 patients with chronic active hepatitis (CAH) and their families were HL-A typed. HL-A8 was significantly increased in frequency. An apparent increased frequency of HL-A1 was shown to be secondary to the increased HL-A8 due to linkage disequilibrium. Genotype analysis revealed a striking increased frequency of homozygosity for HL-A8, 6 of 21 patients (28.5%) vs. 2.8% of controls. Two patients and one normal who were homozygous for both HL-A1 and HL-A8 were found to be homozygous for a mixed lymphocyte culture (MLC) determinant 8a. Homozygous 8a cells were used as test-stimulating cells in one-way MLC reactions to determine the frequency of the expression of the 8a determinant in 17 patients and 49 controls selected for HL-A type. 8a was found to be associated with 50% of HL-A8 haplotypes and was as frequent in the patient and control populations of the same HL-A types. These data suggest that susceptibility to CAH is determined by homozygosity for a gene that is in linkage disequilibrium with HL-A8 and more closely associated with the HL-A second locus then with the locus for the major MLC determinant.

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Section: Genetic Analysis Of Patients With Chronic Active Hepatitiscontrasting

confidence: 53%

Genetic analysis of patients with chronic active hepatitis.

Page¹,

Sharp²,

Greenberg³

et al. 1975

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Studies of adoptive relatives, half-siblings and offsprings of conjugal pairs also supported these data (Ebers et al, 1995;Robertson et al, 1997). In 1975, a relationship between MS and the major histocompatibility complex (MHC) was confirmed (Jersild et al, 1975). Futhermore, through a genomwide linkage study, it was confirmed that the HLA DRB1*15:01 allele is linked to MS susceptibility (GAMES Study, 2003).…”

Section: I3 Pathomechanism Of Mssupporting

confidence: 50%

New data in the epidemiology of multiple sclerosis in Hungary

Fricska-Nagy

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“…There is evidence for a genetic predisposition to develop MS with a sib value of 20 -40 (1). Although the HLA region has proven to be associated with MS (2)(3)(4)(5), it has turned out to be difficult to link distinct genes to MS susceptibility in both family linkage studies and association studies. This difficulty could be attributed to genetic heterogeneity, modest or weak effects of each disease-predisposing gene, and insufficient sample sizes.…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

Advanced Intercross Line Mapping of Eae5 Reveals Ncf-1 and CLDN4 as Candidate Genes for Experimental Autoimmune Encephalomyelitis

Bečanović

Jagodic

Sheng

et al. 2006

The Journal of Immunology

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Eae5 in rats was originally identified in two F2 intercrosses, (DA × BN) and (E3 × DA), displaying linkage to CNS inflammation and disease severity in experimental autoimmune encephalomyelitis (EAE), respectively. This region overlaps with an arthritis locus, Pia4, which was also identified in the (E3 × DA) cross. Two congenic strains, BN.DA-Eae5 and BN.DA-Eae5.R1, encompassing the previously described Eae5 and Pia4, were established. DA alleles within the chromosome 12 fragment conferred an increase in disease susceptibility as well as increased inflammation and demyelination in the CNS as compared with BN alleles. To enable a more precise fine mapping of EAE regulatory genes, we used a rat advanced intercross line between the EAE-susceptible DA strain and the EAE-resistant PVG.1AV1 strain. Linkage analysis performed in the advanced intercross line considerably narrowed down the myelin oligodendrocyte glycoprotein-EAE regulatory locus (Eae5) to a ∼1.3-megabase region with a defined number of candidate genes. In this study we demonstrate a regulatory effect of Eae5 on MOG-EAE by using both congenic strains as well as fine mapping these effects to a region containing Ncf-1, a gene associated with arthritis. In addition to structural polymorphisms in Ncf-1, both sequence polymorphisms and expression differences were identified in CLDN4. CLDN4 is a tight junction protein involved in blood-brain barrier integrity. In conclusion, our data strongly suggests Ncf-1 to be a gene shared between two organ-specific inflammatory diseases with a possible contribution by CLDN4 in encephalomyelitis.

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Histocompatibility Determinants in Multiple Sclerosis

Cited by 60 publications

References 23 publications

Genetic analysis of patients with chronic active hepatitis.

Genetic analysis of patients with chronic active hepatitis.

New data in the epidemiology of multiple sclerosis in Hungary

Advanced Intercross Line Mapping of Eae5 Reveals Ncf-1 and CLDN4 as Candidate Genes for Experimental Autoimmune Encephalomyelitis

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