Genetic association of Ctla-4 to myasthenia gravis with thymoma.
Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) plays a pivotal role in downregulating both the cellular and the humoral response by suppressing ongoing responses of activated T cells. Our earlier study showed that genetic variations in interleukin-1 genes confer susceptibility to myasthenia gravis, especially in patients having the lowest risk from major histocompatibility complex genes. Here we describe an association of Ctla-4 gene to the disease with thymoma and a higher prevalence of CTLA-4 gene polymorphism allele 104 in patients positive for IL-1beta TaqI allele 2, an IL-1beta 'high secretor' phenotype. There was no association in patients with hyperplasia and normal thymic histology. These results further advocate that MG is a polygenetic disease and suggest that co-stimulators such as CTLA-4 and CD28 might have an important role in the pathogenesis of the disease.
Immunological Research Unit, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
D
D
Huang
L
L
Liu
K
K
Norén
S Q
SQ
Xia
J
J
Trifunovic
R
R
Pirskanen
A K
AK
Lefvert
D000069594:Abatacept; D000328:Adult; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics; D060908:CTLA-4 Antigen; D002889:Chromosomes, Human, Pair 2; D002896:Chromosomes, Human, Pair 6; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D006801:Humans; D018796:Immunoconjugates; D008297:Male; D009157:Myasthenia Gravis / Q000150:complications* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012016:Reference Values; D013945:Thymoma / Q000150:complications* / Q000235:genetics*; D013953:Thymus Neoplasms / Q000150:complications* / Q000235:genetics*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D005819:Genetic Markers; D018796:Immunoconjugates; D000069594:Abatacept