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

• Published in: Lupus 2011-05, Vol.20 (6), p.628-635
• Main Authors: Doníz-Padilla, L, Martínez-Jiménez, V, Niño-Moreno, P, Abud-Mendoza, C, Hernández-Castro, B, González-Amaro, R, Layseca-Espinosa, E, Baranda-Cándido, L
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Adapter proteins; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - immunology; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Autoimmune diseases; Case-Control Studies; Genes; Humans; Immunology; Leukocytes, Mononuclear - metabolism; Lupus; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lymphocytes; Mexico; Phosphorylation; Polymerase Chain Reaction; Polymerization; Polymorphism; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-cbl - genetics; Proto-Oncogene Proteins c-cbl - immunology; Proto-Oncogene Proteins c-jun - metabolism; Regulation; Rheumatoid arthritis; T-Lymphocytes - metabolism
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/0961203310394896

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.