Genetic susceptibility to multiple sclerosis

Haegert, David G.; Marrosu, Maria Giovanna

doi:10.1002/ana.410360807

Cited by 30 publications

(16 citation statements)

References 57 publications

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“…Interestingly, frequency rates of MG in Sardinia appear to be similar to rates in other comparable Italian and European investiga tions. This supports the view that MG differs from other autoimmune diseases, such as MS and IDDM, for immunogenetic susceptibility [15][16][17][18], and may have a different pathophys iology in that there are no ethnic differences in MG susceptibility within Europe.…”

Section: >60supporting

confidence: 72%

Epidemiology of Myasthenia gravis in Northwestern Sardinia

et al. 1997

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A previous epidemiological study on myasthenia gravis (MG) in Sardinia indicated a prevalence rate of 4.5 per 100,000 population and an incidence of 0.25 per 100,000 population in the period 1958–1986. This study, however, investigated the entire Sardinian population (about 1,500,000) and the reported rates are likely to be underestimated. Because the use of a very large population has been found to cause major bias in case finding, the present study was designed to overcome this bias by determining the prevalence and incidence of MG in a well-defined area of Northwestern Sardinia, with a population of about 270,000 (1991 census). Potential MG cases were ascertained using all possible medical sources. The diagnosis of MG was based on the clinical, neurophysiological and conventional pharmacological findings (Tensilon test, response to anticholinesterases). On prevalence day (December 31, 1994) 29 MG patients were living in the study area (17 women and 12 men). Since the total population on prevalence day was 268,926 (137,284 women and 131,642 men), the calculated prevalence was 11.1 per 100,000 population (12.4 women and 9.9 men). The present study shows that the risk of MG in Sardinia is higher than previously suggested. The risk, however, is not significantly different from that found in other comparable Italian and European areas. It contrasts with what has been found for other autoimmune diseases such as multiple sclerosis and insulin-dependent diabetes mellitus in Sardinians, both showing frequencies up to 3–5 times higher than in the rest of Italy.

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Section: >60supporting

confidence: 72%

Epidemiology of Myasthenia gravis in Northwestern Sardinia

et al. 1997

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“…33 For example, HLA-DR1 and some forms of HLA-DR4 have been found in majority of patients with rheumatoid arthritis, 34,35 whereas HLA-DR3 predisposed to mixed cryoglobulinemia after hepatitis C infection. 3,4 HLA-DR2 has been described as closely associated with anti-glomerular basement membrane disease, 32 multiple sclerosis, 36 and narcolepsy. 37 In general, HLA linkage to autoimmune disease is believed to arise from an HLA haplotype-determined ability to present pathogenic peptides derived from self-antigens or foreign antigens.…”

Section: Discussionmentioning

confidence: 99%

Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome

Maciejewski

Follmann

Nakamura

et al. 2001

Blood

138

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Many autoimmune diseases are associated with HLA alleles, and such a relationship also has been reported for aplastic anemia (AA). AA and paroxysmal nocturnal hemoglobinuria (PNH) are related clinically, and glycophosphoinositol (GPI)-anchored protein (AP)-deficient cells can be found in many patients with AA. The hypothesis was considered that expansion of a PNH clone may be a marker of immune-mediated disease and its association with HLA alleles was examined. The study involved patients with a primary diagnosis of AA, patients with myelodysplastic syndrome (MDS), and patients with primary PNH. Tests of proportions were used to compare allelic frequencies. For patients with a PNH clone (defined by the presence of GPI-APdeficient granulocytes), regardless of clinical manifestations, there was a higher than normal incidence of HLA-DR2 (58% versus 28%; z ‫؍‬ 4.05). The increased presence of HLA-DR2 was found in all frankly hemolytic PNH and in PNH associated with bone marrow failure (AA/PNH and MDS/PNH). HLA-DR2 was more frequent in AA/PNH (56%) than in AA without a PNH clone (37%; z ‫؍‬ 3.36). Analysis of a second cohort of patients with bone marrow failure treated with immunosuppression showed that HLA-DR2 was associated with a hematologic response (50% of responders versus 34% of nonresponders; z ‫؍‬ 2.69). IntroductionIdiopathic aplastic anemia (AA) shows striking similarities to diseases of other organ systems with classically established autoimmune pathophysiology: AA frequently affects younger individuals, there is laboratory evidence for immune activation and destruction of the target organ by autoreactive T cells, 1 and patients often respond to immunosuppressive therapies. 2 Many autoimmune diseases have clear associations with particular HLA alleles: ankylosing spondylitis with HLA-B27 is the classical example, but similar relationships have been found in psoriasis (HLA-B13, HLA-B17-Cw6), rheumatoid arthritis (HLA-DR1 and HLA-DR4), juvenile diabetes mellitus (HLA-B8, HLA-B15, and HLA-B54), and multiple sclerosis (HLA-B7 and HLA-DR2). In hematology, agranulocytosis secondary to clozapine (HLA-B38, HLA-DR4, and DQw3) or methimazole (HLA-DR8) and mixed cryoglobulinemia in hepatitis C virus-infected patients (HLA-B8 and HLA-DR3) exemplify links between immunogenetics and pathophysiology. [3][4][5][6] Fundamentally, the presence of particular HLA alleles likely allows for preferential presentation of particular peptides, perhaps derived from autoantigens, to specific T cells, driving the autoimmune process.In AA, HLA associations have also been examined. [7][8][9][10][11][12][13][14][15][16][17][18][19] An increased frequency of HLA-DR2 has been reported in some but not all studies. [9][10][11][12][13]16 An association with class I alleles (especially HLA-A2) has been inconsistently identified. 7,10,[13][14][15] The presence of HLA-DR15 (split of DR2) was associated with good response to cyclosporine therapy, suggesting that this allele may be a specific predisposing factor for the development of immune-med...

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“…(2) Postgraduate Student, PhD, University of São Paulo. (3) Diretctor of the Department of Ophthalmology, Santa Casa de São Paulo (4) Assistant of the Department of Neurology, Santa Casa de São Paulo (5) …”

Section: Manifestações Oculares Em Pacientes Com Esclerose Múltipla Ementioning

confidence: 99%

Manifestações oculares em pacientes com esclerose múltipla em São Paulo

Sibinelli¹,

Cohen²,

Ramalho³

et al. 2000

Arq. Bras. Oftalmol.

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Purpose: To study the frequency and characteristics of ocular manifestations in patients with multiple sclerosis (MS) in the state of São Paulo.Methods: From March, 1996 to November, 1998, 64 patients (48 females, 16 males, age 17 -59 years) with MS underwent ophthalmologic examination and computerized visual field perimeter testing.Results: Forty-four (68.75%) of the 64 examined patients presented some kind of ocular manifestation. The most frequent manifestation was optic neuritis (28 patients -43.75%). It was the first manifestation of MS in 18 (28.1%) patients. Alterations of ocular motility were the second most frequent finding. Eight (12.5%) patients suffered from diplopia, of which 6 (9.37%) presented this as their first manifestation of MS. Sixth nerve palsy occurred in 2 patients (3.1%), with esotropia as a first sign of the disease. Other findings can be listed: uveitis (4 patients -6.25%), changes in iridian topography with anterior lens capsule pigmentation (3 patients -4.6%). The most frequent visual field defect in the patients who presented optic neuritis was arcuate scotoma with paracentral defects (46.4%). Two patients presented central scotomas and peripheral changes. None of the patients presented nystagmus.Conclusion: Our data show that ocular findings in MS are frequent and many times are the initial manifestation of this disease. Although optic neuritis was the most frequent finding, we must emphasize the possibility of other ocular manifestations to be either preceding or occuring at the same time as this disease. Manifestações oculares em pacientes com esclerose múltipla em São Paulo

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Genetic susceptibility to multiple sclerosis

Cited by 30 publications

References 57 publications

Epidemiology of Myasthenia gravis in Northwestern Sardinia

Epidemiology of Myasthenia gravis in Northwestern Sardinia

Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome

Manifestações oculares em pacientes com esclerose múltipla em São Paulo

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