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ABSTRACT: beta(2) Adrenoceptor (beta(2)-AR) represents a link between the sympathetic nervous system and the immune system, and may be involved in human rheumatoid arthritis (RA). The gene encoding beta(2)-AR contains three single nucleotide polymorphisms (SNPs) at amino acid positions 16, 27, and 164.
To examine the common variants at positions 16 and 27 and their association with RA.
An allele-specific polymerase chain reaction to determine the common variants at positions 16 and 27 was used in 154 patients with RA and 198 ethnically matched healthy subjects from northern Sweden.
Carriage of Arg16 and of Gln27 was associated with RA. Carriage of Gln27 was associated with activity of the disease and in combination with non-carriage of Arg16 with higher levels of rheumatoid factor.
The beta2-AR SNPs may thus constitute an additional non-major histocompatibility complex association in RA.
Annals of the Rheumatic Diseases 06/2005; 64(5):773-6. · 8.73 Impact Factor
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ABSTRACT: The beta2-adrenergic receptor (beta2-AR) belongs to the group of G-protein coupled receptors and is present mainly on skeletal and cardiac muscle cells and lymphocytes. The gene encoding beta2-AR (ADRB2) displays a moderate degree of heterogeneity in the human population. The distribution of polymorphisms at amino acid positions 16, 27 and 164 is changed in asthma, hypertension and obesity. We have earlier reported a decreased density of the beta2-AR on peripheral blood mononuclear cells and the presence of beta2-AR antibodies in patients with MG. Since certain polymorphisms affect the function of the beta2-AR, it was of interest to analyse these in MG. Using allele-specific polymerase chain reaction amplification, we revealed an over-representation of homozygosity for Arg16 and a lower prevalence of homozygosity for Gly16 in MG patients compared with healthy individuals. The increased frequency of homozygosity for Arg16 was due to a contribution from patients with generalized MG but not from patients with only ocular disease. Homozygosity for Glu27 was negatively associated with both the presence of beta2-AR antibodies and severity of disease. Moreover, acetylcholine receptor (AChR) antibodies were more often present in patients being homozygous for Gln27. Our results imply that homozygosity for Arg16 confers susceptibility to generalized MG, and that certain polymorphisms at amino acid position 27 are associated with subgroups of patients.
Clinical & Experimental Immunology 01/2000; 119(1):156-60. · 3.36 Impact Factor
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ABSTRACT: Myasthenia gravis (MG) is an autoimmune disease characterised by serum anti-acetylcholine receptor (AChR) antibodies and several pathogenic mechanisms for the action of these antibodies have been elucidated. In this study, we have analysed a possible additional mechanism for these antibodies, namely antibody-dependent cell-mediated cytotoxicity (ADCC). Using as target cells a cell line expressing AChR, we could show an increased ADCC mediated by sera from MG patients. Sera with AChR antibodies induced a higher cytotoxicity than sera from patients without these antibodies or healthy individuals. Sera from MG patients with thymoma induced a higher cytotoxic effect than sera from other patients. There was a strong positive correlation between the concentration of AChR antibodies and cytotoxicity mediated by purified IgG fractions from thymoma patients. In addition, there was a higher cytotoxicity mediated by sera from thymoma patients with extended dinucleotide repeats, (AT)n repeats, in the CTLA-4 gene. ADCC mediated by AChR antibodies may thus be another possible pathogenic mechanism that could operate in MG patients, especially in patients with thymoma.
Journal of Neuroimmunology 11/1999; 99(2):183-8. · 2.96 Impact Factor
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ABSTRACT: Patients with myasthenia gravis have antibodies and T cells that react with the beta1- and beta2-adrenergic receptors. These receptors, as well as other auto-antigens, are present on cardiomyocytes, skeletal muscle cells and lymphocytes and are of importance for the regulation of the functions of these organs. Antibodies against the beta1-adrenergic receptor have been implicated in dilated cardiomyopathies. Myasthenia gravis (MG) patients have been suggested to have a higher than normal prevalence of heart disease. We have analysed the isotypes, subclasses, and binding sites of the beta-adrenergic receptors antibodies in both MG patients and healthy individuals and the correlation between beta-adrenergic receptors antibodies and heart disease in MG patients. The patients have IgG antibodies that react with both beta1- and beta2-adrenergic receptors. The subclasses were predominantly IgG2 and IgG4. By using synthesised overlapping peptides representing the immunodominant regions on the receptors, it was shown that the antibodies bound to partially overlapping sites on both beta1- and beta2-adrenergic receptors, but not to peptides from the acetylcholine receptor. beta-adrenergic receptor antibodies were found in 34/125 MG patients. Seven out of these 34 patients had symptomatic heart disease, all seven were over 70 years of age and had arteriosclerotic heart disease. There was no difference in the prevalence of clinical heart disease in patients with and without beta-adrenergic receptor antibodies. However, patients with heart disease had significantly higher levels of antibodies than healthy individuals and other patients. Antibodies against beta-adrenergic receptors in patients with myasthenia gravis binds to both beta1- and beta2-adrenergic receptors and might be implicated in the few patients with myasthenia gravis who have heart disease.
Journal of Neuroimmunology 12/1998; 91(1-2):82-8. · 2.96 Impact Factor
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ABSTRACT: The usage of T cell receptor (TCR) Valpha/Vbeta chains on cells from 38 patients with myasthenia gravis (MG) was determined by flow cytometry. There was a decreased number of cells expressing Vbeta2 in CD8+ and Vbeta3 in CD4+ cells in patients compared with healthy individuals. Abnormal expansions of T cells using particular TCR Valpha/Vbeta gene products were found in 18/38 patients. A significantly higher usage of Vbeta13 was observed but there was no restriction with regard to other TCR Valpha/Vbeta. Expanded cells belonging to both CD4+ and CD8+ were present in MG patients while restricted to the CD8+ population in healthy individuals. To elucidate the role of the expanded populations, we studied characteristics of the expanded and non-expanded T cells from MG patients who had persistent T cell expansions over more than 2 years. The cells were analysed with regard to phenotype, cytokine secretion, cytokine mRNA expression and reactivity with the autoantigen, the acetylcholine receptor. The characteristics of the expanded populations in MG clearly differed from those found in healthy individuals. More cells in the CD4+ expanded populations expressed HLA-DR and there was also a tendency for higher expression of CD25, CD28 and CD57. The number of cells spontaneously secreting cytokines was higher in the expanded populations. A dominant Th1-type cytokine secretion and mRNA expression was noted. Autoantigen-reactive CD4+ T cells were largely restricted to the expanded populations.
Clinical & Experimental Immunology 10/1998; 113(3):456-64. · 3.36 Impact Factor
