Genetic polymorphisms of low molecular weight protein tyrosine phosphatase (LMW-PTP): relationship with erythrocyte enzymatic phenotype in patients with Systemic Lupus Erythematosus

摘要

abstract_textpSystemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disease characterized by the loss of self-tolerance, revealing defective immune regulatory mechanisms./ppACP1 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./ppSeveral 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./ppOur 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./ppThe 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 - chi(2) for 4 freedom degrees). The LMW-PTP median enzymatic activity in the SLE group (260.53 +/- 96.18mmol p-nitro-phenolate/gHb/h) was lower than in the control group (339.84 +/- 113.78mmol p-nitrophenolate/gHb/h) (p 0.001)./ppThese results suggest a relevant role for LMW-PTP in the context of SLE, namely at cellular proliferation and oxidative stress level./p/abstract_text