title: Expression and function of Cbl-b in T cells from patients with systemic lupus erythematosus, and detection of the 2126 A/G Cblb gene polymorphism in the Mexican mestizo population.
abstract: Systemic lupus erythematosus (SLE) is characterized by abnormalities in the function of T and B lymphocytes and in the signaling pathways induced through their receptors. Cbl-b is an intracellular adaptor protein that plays a key role in the negative regulation of lymphocyte activity. We explored the expression and function of Cbl-b in T lymphocytes from SLE patients. In addition, the possible association of SLE and a single nucleotide polymorphism (SNP) of the Cblb gene was determined. We studied 150 SLE patients, 163 healthy individuals, and 14 patients with rheumatoid arthritis (RA). The expression of Cbl-b was analyzed in the peripheral blood mononuclear cells, and the negative regulatory function of Cbl-b was assessed by analyzing actin polymerization and the phosphorylation of JNK and c-Jun induced through CD3. Furthermore, the 2126(A/G) SNP of the Cblb gene was detected by real-time polymerase chain reaction. We found a significant small reduction in the expression of Cbl-b as well as increased levels of activation of c-Jun and actin polymerization in T lymphocytes from patients with SLE compared with healthy controls or RA patients. In addition, a significant association between the 2126(A/G) SNP and SLE was detected. Our data suggest that Cbl-b may contribute to the deregulated activation of T lymphocytes observed in SLE.
authors.affiliation: Department of Immunology, School of Medicine, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico.
authors.forename: L
authors.initials: L
authors.lastname: Doníz-Padilla
authors.forename: V
authors.initials: V
authors.lastname: Martínez-Jiménez
authors.forename: P
authors.initials: P
authors.lastname: Niño-Moreno
authors.forename: C
authors.initials: C
authors.lastname: Abud-Mendoza
authors.forename: B
authors.initials: B
authors.lastname: Hernández-Castro
authors.forename: R
authors.initials: R
authors.lastname: González-Amaro
authors.forename: E
authors.initials: E
authors.lastname: Layseca-Espinosa
authors.forename: L
authors.initials: L
authors.lastname: Baranda-Cándido
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008800:Mexico; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D058105:Polymerization; D020641:Polymorphism, Single Nucleotide; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics* / Q000276:immunology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D016755:Proto-Oncogene Proteins c-jun; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl