Acetylcholine Receptor Antibody Titer and HLA-B8 Antigen in Myasthenia Gravis

Keesey, John; Naiem, Faramarz; Lindstrom, Jon; Roe, Denise J.; Herrmann, Christian; Walford, Roy L.

doi:10.1001/archneur.1982.00510140007002

Cited by 16 publications

(5 citation statements)

References 22 publications

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“…Among the Japanese, the prevalence of ocular and generalized MG was nearly the same, but ocular MG occurred mostly in children and generalized MG mostly in adults E12). The AChR Ab titer was shown to be much lower in ocular than in generalized MG by our previous study 1171 and by others 16,19,201. The prevalence of autoantibodies other than AChR Ab differed between patients with the ocular and generalized forms C131, and it was increased in HLA-B8-positive patients C9, 351.…”

mentioning

confidence: 66%

Heterogeneity in myasthenia gravis: HLA phenotypes and autoantibody responses in ocular and generalized types

Kida

Hayashi

Yamada

et al. 1987

Annals of Neurology

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HLA phenotypes and autoantibody responses were studied in 71 Japanese patients with myasthenia gravis. HLA-A2, Bw61, and DRw9 were associated with ocular myasthenia gravis (corrected p [CP] less than 0.05 relative risk [RR] = 2.88; CP less than 0.02, RR = 3.60; and CP less than 0.001, RR = 4.63, respectively) and HLA-DRw8 was associated with generalized myasthenia gravis (CP less than 0.001, RR = 5.40). Neither HLA-B8 nor DR3 was found in Japanese patients. The titer of antiacetylcholine receptor antibody (AChR Ab) and the incidence of autoantibodies other than AChR Ab were higher in patients with generalized myasthenia gravis than in those with the ocular type (2.77 +/- 0.62 versus 0.17 +/- 0.03 pmol/ml, p less than 0.001; and 60.6 versus 29.0%, p less than 0.02, respectively). Patients with a high titer of AChR Ab or with autoantibodies had an increased frequency of HLA-DRw8 (CP less than 0.02, RR = 4.61, and CP less than 0.005, RR = 4.53, respectively); whereas patients with a low titer of AChR Ab or without autoantibodies had an increased frequency of HLA-DRw9 (CP less than 0.001, RR = 8.26, and CP less than 0.005, RR = 4.08, respectively). These findings suggest that ocular and generalized myasthenia gravis might have different immunogenetic backgrounds.

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mentioning

confidence: 66%

Heterogeneity in myasthenia gravis: HLA phenotypes and autoantibody responses in ocular and generalized types

Kida

Hayashi

Yamada

et al. 1987

Annals of Neurology

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“…A new hypothesis 1 (Adler, 1966) Myasthenia gravis bei eineiigen Zwillingen 1 (Haralanov & Kutchonkov, 1966) Myasthenie familiale (pere et fille) avec 1 hyperplasie du thymus (Osborne & Simcock, 1966) Myasthenia gravis in identical twins 1 (Motoki et al, 1966) A case of myasthenia gravis in identical twin 1 brothers (DeGroot et al, 1967) Remission of myasthenia gravis and 1 thyrotoxicosis after thymectomy (Herman, 1969) Familial myasthenia gravis 1 (Hokkanen, 1969) Myasthenia gravis. A clinical analysis of the 1 total material from Finland and special reference to endocrinological and neurological disorders (Herrmann, 1971) The familial occurrence of myasthenia gravis 1 1 (Namba et al, 1971b) Myasthenia gravis occurring in twins 1 1 (Bundey, 1972) A genetic study of infantile and juvenile 1 1 myasthenia gravis (Keesey et al, 1982) Acetylcholine receptor antibody titer and 1 HLA-B8 antigen in myasthenia gravis (Pirskanen, 1977) Genetic aspects in myasthenia gravis. 1 A familial study of 164 Finnish patients (Michalski et al, 1978) Monozygotic twins with Klinefelter's 1 snydrome discordant for systemic lupus erythematosus and symptomatic myasthenia gravis (Seybold & Lindstrom, 1981) Antiacetylcholine receptor antibody and its 1 relationship to HLA type in asymptomatic siblings of a patient with myasthenia gravis (Allen et al, 1984) Myasthenia gravis in monozygotic twins.…”

Section: Determination Of Genetic Regions Inheritedmentioning

confidence: 99%

Utilizing Twins Concordance Rates to Infer the Predisposition to Myasthenia Gravis

Ramanujam¹,

Pirskanen

Ramanujam

et al. 2011

Twin Res Hum Genet

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Myasthenia gravis (MG) is an autoimmune disorder in which patients experience muscular fatigability due to the presence of anti-acetylcholine receptor (AChR) antibodies which inhibit signal transduction across the neuro-muscular junction. Like all complex disorders, disease is caused by an interaction between genetic and environmental factors. Although several genes have been identified which appear to be associated with MG, both classic twin studies and current multi-gene models are insufficient to explain either disease pathogenesis or inheritance. We examined the literature on MG to determine both mono- and dizygotic twin concordance rates, and used this data to (1) estimate the proportion of the population with underlying genetic predisposition to MG and the frequency of the environmental component and (2) derive the number of inherited genetic regions that are required to confer predisposition to MG. Using a MZ twin concordance rate of 35.5%, and a dizygotic rate of approximately 4–5% (based on family data), the probability of encountering environmental components necessary to develop MG in an individual with genetic predisposition is approximately 52.4%, making the frequency of predisposition (1:5240) roughly twice the rate of incidence. Furthermore, the number of genetic regions co-inherited between affected individuals is between two and four, which may be large haplotypes with interacting activity. Determining these haplotypes, by fully sequencing associated regions in cases and controls to identify mutations present, may therefore be a practically step toward the understanding of complex disease.

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“…It has been proposed that Ia antigens on macrophages involved in antigen recognition are a critical genetic factor controlling susceptibility to EAMG. Concentration of antibodies to AChR in the sera of MG patients positive for HLA-B8 is higher than for others, and for patients positive for HLA-DRW3 a similar but smaller increase has also been noted [83]. Numerous diseases have been noted to occur in association with MG, most of which appear to be autoimmune in origin.…”

Section: Clinical Manifestationsmentioning

confidence: 55%

“…Some association between HLA type and MG has been noted. HLA B8 is over-represented in patients developing MG before the age of 35 years [83,158]. HLA-A 2 [543 and HLA-A 3 [55] have both been reported to be associated with thymoma in older patients.…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Immunopathology of acetylcholine receptors in myasthenia gravis

Seybold

Lindstrom

1982

Springer Semin Immunopathol

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It is now clear that the muscular weakness and fatigability seen in MG result from an antibody-mediated immune response to AChR. The mechanisms by which antibodies impair transmission are moderately well understood and detection of antibodies in patient's sera is a reliable diagnostic test for the disease. The spectrum of antibody specificities produced in MG is also beginning to be understood, largely through the use of antibodies produced in the experimental model EAMG. Treatment for MG continues to rely heavily on the symptomatic relief afforded by acetylcholinesterase inhibitors. However, the recent recognition of the autoimmune nature of MG has led to increased emphasis on immunosuppression and antibody removal with some beneficial effects. Despite all that has been learned, the level of ignorance has just been pushed back one step--from the neuromuscular junction to the immune system. What initiates the immune response to AChR in MG and how to specifically suppress this aberrant response remain completely unknown.

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Acetylcholine Receptor Antibody Titer and HLA-B8 Antigen in Myasthenia Gravis

Cited by 16 publications

References 22 publications

Heterogeneity in myasthenia gravis: HLA phenotypes and autoantibody responses in ocular and generalized types

Heterogeneity in myasthenia gravis: HLA phenotypes and autoantibody responses in ocular and generalized types

Utilizing Twins Concordance Rates to Infer the Predisposition to Myasthenia Gravis

Immunopathology of acetylcholine receptors in myasthenia gravis

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