Systemic lupus erythematosus patients under immunosuppressive treatment express high levels of the immunoglobulin lambda variable IGLV8S1 gene with silent somatic mutations.
Biochim Biophys Acta
; 1586(1): 108-12, 2002 Jan 02.
Article
em En
| MEDLINE
| ID: mdl-11781155
ABSTRACT
Systemic lupus erythematosus (SLE) patients express high titers of somatically mutated serum autoantibodies against nuclear structures including double-stranded DNA. These somatic mutations accumulate codons for basic amino acids in the immunoglobulin variable regions of both, heavy and light chains, facilitating binding to nucleic acids. The variable (V) immunoglobulin lambda 8 (IGLV8S1) gene contributes to autoreactive B-cell repertoire of auto-immune patients. Accumulation of immune complexes of these anti-DNA autoantibodies causes severe systemic inflammation in SLE. The current treatment of lupus disease is based on immunosuppressive drugs, but the precise role for this therapy remains to be defined. To evaluate the in vivo effect of combined immunosuppressive treatment on B-lymphocytes repertoire of SLE patients, we have developed an approach using the IGLV8S1 gene as a marker. The transcription of this gene in treated SLE patients was increased. However, we observed a trend, in these patients, to conserve complementarity determining regions (CDRs) and framework regions (FRs) of Vlambda8 polypeptide light chain deduced sequence, from its germline counterpart. Sequencing IGLV8S1 cDNA of untreated SLE patients, taken as a control for treatment effect, displayed a decreased frequency of silent somatic mutations (consequently high frequency of replacement mutations) in the Vlambda8 polypeptide chain deduced sequence. These data suggest that the immunosuppressive drug treatment modulates the positive selection of somatically mutated Vlambda8 light chain.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Região Variável de Imunoglobulina
/
Cadeias lambda de Imunoglobulina
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Imunossupressores
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Lúpus Eritematoso Sistêmico
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Brasil