RESUMO
BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system in genetically susceptible persons. Fcγ receptors (FcγR) are involved in autoimmune diseases. PATIENTS AND METHODS: Sixteen Norwegian patients with relapsing-remitting MS (RRMS) were studied to see whether treatment with either interferon-beta (INF-ß) or glatiramer acetate (GA) influenced the proportion of FcγR1a, FcγR2a, and FcγR3b positive monocytes, granulocytes, or lymphocytes or FcγR1a, FcγR2a, and FcγR2b mRNA levels in leukocytes. One hundred and twenty-seven patients with RRMS and 54 Norwegian healthy blood donors were also analyzed for FcγR2b polymorphisms. RESULTS: Interferon-beta or GA treatment initiated an increase in the proportion of FcγR positive lymphocytes, but did not cause major influence of the long-term proportion of FcγR positive leukocytes or their FcγR mRNA levels. No significant differences were observed between RRMS patients and healthy controls for the genotype and allele frequencies of FcγR2b polymorphisms. DISCUSSION: INF-ß or GA treatment probably has no major role in the regulation of FcγRs on immune cells in RRMS. Furthermore, polymorphisms of the inhibitory FcγR2b do not seem to influence the susceptibility for MS.
Assuntos
Esclerose Múltipla/tratamento farmacológico , Receptores de IgG/imunologia , Adjuvantes Imunológicos/uso terapêutico , Adulto , Feminino , Acetato de Glatiramer , Humanos , Fatores Imunológicos/imunologia , Interferon beta/uso terapêutico , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Noruega , Peptídeos/uso terapêutico , Polimorfismo Genético , Resultado do TratamentoRESUMO
The level of interleukin-10 (IL-10) expression is related to polymorphisms -1082 (G/A), -819 (T/C) and -592 (A/C) in the promoter region of the IL-10 gene, which constitute three haplotypes, GCC, ATA, and ACC. The ATA (a non-GCC) haplotype, which is associated with low IL-10 expression, has been shown to improve interferon (IFN) treatment response in hepatitis C. We analysed the distribution of IL-10 promoter haplotype combinations to determine whether they could influence initial IFN treatment response in 63 patients with relapsing-remitting multiple sclerosis (MS). The patients were grouped into non-GCC or GCC haplotypes, and the clinical and magnetic resonance imaging (MRI) disease activity was compared in the two groups. During the first 6 months of treatment, MS patients with non-GCC haplotypes experienced fewer new MRI T1-contrast enhancing lesions [0.77+/-0.36 (SEM)] than patients with the GCC haplotype (2.45+/-0.57) (P=0.05, Mann-Whitney U test). No differences were detected on clinical disease activity. The results suggest an influence of IL-10 promoter polymorphisms on IFN treatment response in MS.
Assuntos
Resistência a Medicamentos/genética , Haplótipos/genética , Interferons/farmacologia , Interleucina-10/genética , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/genética , Adulto , Sequência de Bases/genética , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Análise Mutacional de DNA , Progressão da Doença , Resistência a Medicamentos/imunologia , Feminino , Testes Genéticos , Humanos , Interferons/uso terapêutico , Interleucina-10/imunologia , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla/imunologia , Fibras Nervosas Mielinizadas/imunologia , Fibras Nervosas Mielinizadas/patologia , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genéticaRESUMO
Interleukin-10 (IL-10) may have both pro- and anti-inflammatory effects in Guillain-Barré syndrome (GBS). The distribution of polymorphisms in the IL-10 gene (-1082 (G/A), -819 (T/C) and -592 (A/C)) was analysed to determine whether they could influence disease susceptibility or clinical course in GBS. The -592 CC and -819 CC genotypes associated with increased IL-10 response were more frequent in the GBS patients than in the controls (P=0.027), but the polymorphisms did not influence the clinical course of the disease.
