title: [Genetic polymorphisms of low molecular weight protein tyrosine phosphatase (LMW-PTP): relationship with erythrocyte enzymatic phenotype in patients with Systemic Lupus Erythematosus].
abstract: Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disease characterized by the loss of self-tolerance revealing defective immune regulatory mechanisms. ACP1 is a highly polymorphic erythrocyte LMW-PTP isozyme encoded by a gene presenting three alleles (A B C). These alleles determine different fast slow isozyme proportions having distinct cellular localization and biological functions. Several studies demonstrated the involvement of LMW-PTP in the PDGFr, IL4 and insulin dependent cellular signalling regulation. The most relevant phenotypic effects of LMW-PTP over expression are the strong reduction of cell growth rate in response to PDGF stimulation together with up regulation of cell adhesion and chemotaxis. Our aims were the characterization of LMW-PTP genetic polymorphisms and the evaluation of erythrocyte LMW-PTP enzymatic activity in a lupus and a control population group and the determination of genotype phenotype relationship in SLE. The results revealed a predominance of AA (n=8) and AB (n=21) genotypes in SLE which are responsible for the low enzymatic activity forms while in the control group there was a predominance of high enzymatic activity genotypes AB (n=52) and BB (n=36). The difference between the two groups was statistically significant (p=0,04 - chi2 for 4 freedom degrees). The LMW-PTP median enzymatic activity in the SLE group (260.53+/-96.18mmol p-nitrophenolate/gHb/h) was lower than in the control group (339.84+/-113.78mmol p-nitrophenolate/gHb/h) (p<0.001). These results suggest a relevant role for LMW-PTP in the context of SLE namely at cellular proliferation and oxidative stress level.
authors.affiliation: Laboratorio de Imunologia Inst. Nac. Saúde Dr. Ricardo Jorge-Lisboa. fmartins@insa.min-saude.pt
authors.forename: Maria de Fátima Araújo
authors.initials: Mde F
authors.lastname: Esteves Martins
authors.forename: Raquel
authors.initials: R
authors.lastname: Carvalho
authors.forename: Miguel
authors.initials: M
authors.lastname: Alves
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Monteiro da Silva Ferreira
authors.forename: Manuel Diamantino
authors.initials: MD
authors.lastname: Pires Bicho
mesh_terms: D000328:Adult; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D011518:Proto-Oncogene Proteins; C490429:ACP1 protein, human; D017027:Protein Tyrosine Phosphatases