The influence of HLA-DR and -DQ alleles on progression to multiple sclerosis following a clinically isolated syndrome

Ma, Kelly; Da, Cavan; Penny, Melissa A.; Mijovic, C.; Jenkins, David; Morrissey, S. P.; Miller, DH; Barnett, A H; Da, Francis

doi:10.1016/0198-8859(93)90184-3

Cited by 38 publications

(19 citation statements)

References 27 publications

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“…Several other studies examined the possible relationship between HLA status and MRI findings at disease onset [18,21,26,41,54,55]. The results drawn from these studies are consistent.…”

Section: Introductionsupporting

confidence: 69%

HLA genotypes and disease severity assessed by magnetic resonance imaging findings in patients with multiple sclerosis

Zivadinov

Uxa²,

Zacchi³

et al. 2003

J Neurol

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The objective of the study was to examine the relationship between HLA genotypes and disease severity as measured by brain MRI quantitative markers of demyelinating and destructive pathology in patients with multiple sclerosis (MS). We studied 100 patients with MS and 122 age, sex-, ethnic- and residence-matched controls. The DNA extraction and the genomic typing (A, B, DRB1 and DQB1 loci) were obtained with sequence-specific oligonucleotide method, using a commercially available reversible line blot assay (INNO-LIPA). All patients underwent a 1.5 tesla MRI examination of the brain. Disease severity was assessed by clinical (Expanded Disability Status Scale (EDSS)) and MRI (T2- and T1-lesion load (LL) and brain parenchymal fraction (BPF)) outcome measures. HLA-DQB1* 02 (OR 19.9, 95% C. I. 16.2-24.3, uncorrected (uncorr)- p<0.00001, corr-p<0.0006), -DQB1*03 (OR 16.8, 95% C. I. 13.6-20.5, uncorr-p<0.00001, corrp< 0.0006), -DRB1*15 (OR 4.6, 95% C. I. 3.7-5.6, uncorr-p= 0.0001, corr-p=0.006), and -DRB1*03 (OR 3.9, 95% C. I. 3.2-4.8, uncorr-p=0.0001, corr-p= 0.006) alleles were associated with MS. T2-, T1-LL, BPF and EDSS were not significantly different according to the carrier status of these HLA alleles. No differences were found in the ratios of disease severity/disease duration according to the HLA carrier status. Multiple regression analysis showed that a higher T2-LL was associated with the presence of DRB1*04 (uncorr-R2=0.15, p=0.006 and corr-R2=0.11, p=0.025) and B7 alleles (uncorr-R2=0.08, p=0.02 and corr-R2=0.07, p=0.018), T1-LL was associated with B7 (uncorr-R2=0.30, p<0.0001 and corr-R2=0.27, p=0.0001) and DRB1*12 (uncorr-R2=0.25, p<0.0001 and corr-R2=0.21, p=0.0002) alleles, whereas the BPF was predicted only by the presence of DRB1*12 allele (uncorr-R2=0.24, p=0.002 and corr-R2=0.20, p=0.004). The study findings suggest that some HLA alleles may predict the destructive pathological processes visible on MRI. Since the size of the sample studied is relatively small, further studies are needed to draw any firm conclusion about genotype/phenotype correlation in patients with MS.

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“…Several other studies examined the possible relationship between HLA status and MRI findings at disease onset [18,21,26,41,54,55]. The results drawn from these studies are consistent.…”

Section: Introductionsupporting

confidence: 69%

HLA genotypes and disease severity assessed by magnetic resonance imaging findings in patients with multiple sclerosis

Zivadinov

Uxa²,

Zacchi³

et al. 2003

J Neurol

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“…This study has employed PCR methods to confirm the recognised association of ON with the DR15 phenotype in this Irish patient group. This susceptibility association with the DR15 phenotype has previously been identified in ON studies performed in Sweden,1 3 11 13 14 the USA,5 Denmark,6 the UK8 12 and Australia 16…”

Section: Discussionsupporting

confidence: 57%

“…The lesions observed in ON are virtually identical to those seen in MS 8. A study of childhood ON (94 cases under 16 years of age) suggests a lower risk of progression to MS (13% at 10 years, 26% by 40 years) compared to adults 9.…”

mentioning

confidence: 68%

“…Whilst it is evident that approximately half of adult ON patients will go on to develop MS, it is also apparent that others do not 10 – 12. An increased frequency of the MS-associated DR15 haplotype has been demonstrated in studies performed in Sweden,7 10 11 13 14 the USA,15 Denmark,6 the UK8 12 and Australia 16. In contrast, the frequency of both HLA DRB1*07 and DRB1*11 were found to be higher in Iranian patients 17.…”

mentioning

confidence: 99%

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The relationship between HLA-DRB1 alleles and optic neuritis in Irish patients and the risk of developing multiple sclerosis

Tuwir

Dunne²,

Crowley³

et al. 2007

British Journal of Ophthalmology

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“…However, the existence of genetic determinants of relapse frequency has not been proven as yet. It was previously reported that the major histocompatibility locus that has the strongest association with susceptibility to MS, HLA-DRB1 * 1501, may also be associated with the probability of conversion to definite MS in patients with a CIS [49] . In another study, three susceptibility loci were associated with relapse severity: MPHOSPH9 positively, and RGS1 and TNFRSF1A negatively [50] .…”

Section: Individual Risk Factors and Predictorsmentioning

confidence: 99%

Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review

Kalinčík

2015

Neuroepidemiology

139

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Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS phenotype. While their diagnostic value relates predominantly to the definition of clinically definite MS, their prognostic value is determined by their relatively high associated risk of incomplete remission resulting in residual disability. The mechanisms governing a relapse incidence are unknown, but numerous modifiers of relapse risk have been described, including demographic and clinical characteristics, many of which represent opportunities for improved disease management. Also relapse phenotypes have been associated with patient and disease characteristics and an individual predisposition to certain phenotypic presentations may imply individual neuroanatomical disease patterns. While immunomodulatory therapies and corticosteroids represent the mainstay of relapse prevention and acute management, respectively, their effect has only been partial and further search for more efficient relapse therapies is warranted. Other areas of research include pathophysiology and determinants of relapse incidence, recurrence and phenotypes, including the characteristics of the relapsing and non-relapsing multiple sclerosis variants and their responsiveness to therapies.

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The influence of HLA-DR and -DQ alleles on progression to multiple sclerosis following a clinically isolated syndrome

Cited by 38 publications

References 27 publications

HLA genotypes and disease severity assessed by magnetic resonance imaging findings in patients with multiple sclerosis

HLA genotypes and disease severity assessed by magnetic resonance imaging findings in patients with multiple sclerosis

The relationship between HLA-DRB1 alleles and optic neuritis in Irish patients and the risk of developing multiple sclerosis

Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review

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