HLA and heterogeneity of multiple sclerosis

Engell, Tine; Raun, Niels E.; Thomsen, Mögens; Platz, P.

doi:10.1212/wnl.32.9.1043

Cited by 42 publications

(12 citation statements)

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“…24 26 But this finding is also unconfirmed and other investigators report that the DR15 phenotype carries a worse prognosis [31][32][33] whereas, as in the present study, most surveys have found no association between HLA and disease outcome. 21 34 However, many of these studies depended on a small sample size and did not use consistent classifications for patient ascertainment.…”

Section: Discussionsupporting

confidence: 44%

HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis

Hensiek

Sawcer

Feakes

et al. 2002

Journal of Neurology, Neurosurgery &Amp; Psychiatry

151

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Section: Discussionsupporting

confidence: 44%

HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis

Hensiek

Sawcer

Feakes

et al. 2002

Journal of Neurology, Neurosurgery &Amp; Psychiatry

151

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“…Analysis of HLA antigen subtypes demonstrated an increased frequency of HLA-DR2 in both the benign and severe forms of the disease compared with control patients, but an association between DR3 and the absence of disease progression was found. Although the association between DR3 and benign MS has been observed in other populations (16), some investigators (17,18) have found no correlation, or the opposite association, i.e., progressive disease with DR3 (19).…”

Section: Introductionmentioning

confidence: 99%

Expression of the human histocompatibility leukocyte antigen DR3 transgene reduces the severity of demyelination in a murine model of multiple sclerosis.

et al. 1998

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The role of various MHC genes in determining the progression of multiple sclerosis (MS) remains controversial. The HLA-DR3 gene has been associated with benign relapsing MS in some genetic epidemiologic studies, but with disease progression in others. We induced demyelination in highly susceptible B10.M and B10.Q mice expressing the DR3 (HLA-DRB1*0301) transgene to determine directly the effects of a human transgene by infecting them with Theiler's murine encephalomyelitis virus (TMEV). DR3 ϩ mice experienced a dramatic reduction in the extent and severity of demyelination compared with DR3 Ϫ littermate controls, whereas anti-TMEV antibody titers, delayed-type hypersensitivity responses, and levels of infectious virus, virus antigen, and virus RNA were similar in both groups. To address a possible mechanism of how the human transgene is reducing virus-induced demyelination, we analyzed cytokine expression in the lesions and also determined whether B10.

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“…The DR2 antigen has been linked to rapidly progressive MS [13], A1 and B8 antigens to progressive outcome, B7 and DR2 antigens to remitting forms, the joint association of A3-B7-DR2 to a benign outcome [14], DRW17 and DQW2 (DR3) to a relapsing-remitting course [15] and DR4 and DQ8 to a primary progressive form [16]. A recent study [17], however, did not find any link between DR15(2), DQ6(1), DR17(3), DR1 and DQ5 and prognosis.…”

Section: Introductionmentioning

confidence: 99%

Study of HLA as a Predisposing Factor and Its Possible Influence on the Outcome of Multiple Sclerosis in the Sanitary District of Calatayud, Northern Spain

Pina

Ara²,

Lasierra³

et al. 1999

Neuroepidemiology

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The relationship between multiple sclerosis (MS) and the HLA antigens DR2 and DQ1 is well recognised, but, in Spain, it has not been clearly defined. The aim of our study was to investigate the relationship between MS and HLA antigens in the sanitary district of Calatayud, northern Spain, and to correlate these antigens with the progression of the disease. Thirty-four patients were selected from a long-term (October 1990 to July 1996) prospective survey in the region where there was a prevalence rate of 58 per 100,000 population. The HLA antigens were determined in 31 patients. A control group of 895 people of Caucasian race was recruited from the same population. We performed serologic tests on all participants. Nucleotide typing was carried out in DR2-positive patients. The most frequent antigens in excess in MS were: A19 (odds ratio, OR: 2.29, p = 0.04), B5 (OR: 2.85, p = 0.02), B41 (OR: 7.65, p = 0.04), CW7 (OR: 3.4, p = 0.004), DR6 (OR: 6.18, p = 0.0001) and DR10 (OR: 3.4, p = 0.004). The DR2 antigen was also more frequent in MS patients (39%) than in controls (19%; OR: 2.69, p = 0.01). All positive DR2 patients showed the DR15(2) split but not the DR16(2) split. The frequency of antigens CW4 and DR1 was lower in MS patients than in controls. The CW4 antigen was detected in 12% of the patients and in 33% of the controls (OR: 0.28, p = 0.04). The DR1 antigen was found in 20% of the controls and in none of the MS patients (OR: undefined, p = 0.01). The DQ1 antigen was observed in 68% of the patients and in 50% of the controls (OR: 2.1, p = 0.07). We did not find any relationship between HLA antigens and progression of the disease. Although we found that DR2 antigen is linked to MS, we also found other antigens related to the disease. This suggests a genetic heterogeneity in our geographic area. We also concluded that the DR1 antigen may play a protective role, as it was detected in 20% of the controls and in none of the MS cases.

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HLA and heterogeneity of multiple sclerosis

Cited by 42 publications

References 0 publications

HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis

HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis

Expression of the human histocompatibility leukocyte antigen DR3 transgene reduces the severity of demyelination in a murine model of multiple sclerosis.

Study of HLA as a Predisposing Factor and Its Possible Influence on the Outcome of Multiple Sclerosis in the Sanitary District of Calatayud, Northern Spain

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