Dataset Information

Concomitant autoimmunity in myasthenia gravis--lack of association with IgA deficiency.

ABSTRACT: A marked increase in concomitant autoimmune diseases has previously been noted in patients with myasthenia gravis (MG). We show that these diseases occur both before and after the onset of MG and that the process is not influenced by thymectomy. IgA deficiency (IgAD), which is strongly associated with the same HLA haplotype as early onset MG, has recently been suggested to be an autoimmune disease. However, there was no increase in the prevalence of IgAD in a large cohort of Swedish MG patients.

SUBMITTER: Ramanujam R

PROVIDER: S-EPMC3230785 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Concomitant autoimmunity in myasthenia gravis--lack of association with IgA deficiency.

Ramanujam Ryan R Piehl Fredrik F Pirskanen Ritva R Gregersen Peter K PK Hammarström Lennart L

Journal of neuroimmunology 20110612 1-2

A marked increase in concomitant autoimmune diseases has previously been noted in patients with myasthenia gravis (MG). We show that these diseases occur both before and after the onset of MG and that the process is not influenced by thymectomy. IgA deficiency (IgAD), which is strongly associated with the same HLA haplotype as early onset MG, has recently been suggested to be an autoimmune disease. However, there was no increase in the prevalence of IgAD in a large cohort of Swedish MG patients. ...[more]

PMID: 21669464

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Project description:Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction, whose clinical hallmark is muscle weakness and early fatigability. Azathioprine (AZA) is commonly used in Myasthenia Gravis therapy. AZA is a purine antagonist, which inhibits the cell cycle in the resting and DNA synthesis phases. It is usually used as an immunosuppressant to block T- and B-cell proliferation. AZA, bioconverted to 6-mercaptopurine by glutathione S-transferase (GST), can be metabolized either through the hypoxanthine phosphoribosyl transferase pathway to active 6-thioguanine nucleotides (6-TGN) or through the thiopurine S-methyltransferase (TPMT) pathway to inactive methyl-thiopurine metabolites. The incorporation of active 6-TGNs into DNA, causing breaks in DNA strands resulting in interference with RNA production and thereby protein synthesis, is responsible for the drug effect. The response to AZA is determined by which metabolic pathway is being favored. While balanced use of both HPRT and TPMT pathways results in responsiveness to AZA, hyperactivity of TPMT skews the balance towards the TPMT pathway and results in unresponsiveness to AZA with no pharmacological effect. In contrast, low TPMT activity skews the balance towards the HPRT pathway, resulting in increasing side-effects due to the accumulation of 6-TGNs. Current treatments for MG therapy are often inadequate because less than 40% of patients achieve complete remission with available drugs. This reflects the lack of drugs acting on target sites for which there is strong evidence of pathogenicity and the inability to identify responder patients. No criteria for responsiveness are available, exposing patients to unpredictable failures and unpredictable side effects. These individuals are at particular risk for adverse drug reaction (ADRs) or therapeutic failure. Genetic profiling with the Affymetrix drug metabolizing enzymes and transports genotyping array offers the ability to determine 1,931 variants and 225 genes involved in drug metabolism and disposition. Accordingly, the study of well-known drug-metabolizing genes can be involved in the specific metabolic pathway of a drug, which is more likely to define genotype-phenotype association and thereby genotype profiles relevant to drug response that can be applied as predictive biomarkers for pharmacological treatment.

Dataset Information

Concomitant autoimmunity in myasthenia gravis--lack of association with IgA deficiency.

Publications

Concomitant autoimmunity in myasthenia gravis--lack of association with IgA deficiency.

Similar Datasets

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