Using cDNA microarrays to identify human CD19(+) B cell gene products (ESTs) originated from systemic lupus erythematosus susceptibility loci.
Systemic lupus erythematosus (SLE) is a prototype of autoimmune disease which arises from interactions between susceptibility genes and environmental factors. Despite the heterogeneous manifestations in this disease, all SLE patients present plasma autoantibodies recognizing nuclear components. Thus, auto reactive B cells represent key effectors to be investigated. Human linkage analysis is providing the localization of susceptibility loci distributed in chromosomes contributing to elucidate the manner in which interactions between these loci mediate SLE pathogenesis. We associate the cDNA microarray technology to investigate the differential gene expression of CD19(+) B cells with genetic linkage data. Bioinformatics programs served to evidentiate the differentially expressed sequences and the design of the microarray allowed hierarchical clustering of patients and controls. Sequencing allowed the identification of 8 new gene products differentially expressed (ESTs) that were co-localized in SLE or other autoimmune diseases susceptibility loci on chromosome 1p21, 2q21, 13q33, 16p12.1 and 16q12.1. These findings strongly suggest that chromosomal regions previously identified as SLE susceptibility loci are in fact transcribed in CD19(+) B cells of patients. In this review, we delineate a new possibility for the use of cDNA microarrays in studies focusing the control of gene expression of disease susceptibility loci identified by genetic linkage.
Trevisan
Glauce L
GL
Molecular Immunogenetics Group, Department of Genetics, Faculty of Medicine, University of São Paulo (USP), 14040-900 Ribeirão Preto, SP, Brazil.
Rassi
Diane M
DM
Baião
Ana M T
AM
Sandrin-Garcia
Paula
P
Mello
Stephano S
SS
Tamia-Ferreira
Márcia C
MC
Junta
Cristina M
CM
Fachin
Ana L
AL
Marques
Márcia M C
MM
Sakamoto-Hojo
Elza T
ET
Donadi
Eduardo A
EA
Passos
Geraldo A S
GA
D018941:Antigens, CD19 / Q000235:genetics* / Q000276:immunology; D015870:Gene Expression; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*
D018941:Antigens, CD19