RESUMO
The heat shock protein [Hsp] family guides several steps during protein synthesis, are abundant in prokaryotic and eukaryotic cells, and are highly conserved during evolution. The Hsp60 family is involved in assembly and transport of proteins, and is expressed at very high levels during autoimmunity or autoinflammatory phenomena. Here, the pathophysiological role of the wild type [WT] and the point mutated K(409)A recombinant Hsp65 of M. leprae in an animal model of Systemic Lupus Erythematosus [SLE] was evaluated in vivo using the genetically homogeneous [NZBxNZW]F(1) mice. Anti-DNA and anti-Hsp65 antibodies responsiveness was individually measured during the animal's life span, and the mean survival time [MST] was determined. The treatment with WT abbreviates the MST in 46%, when compared to non-treated mice [p<0.001]. An increase in the IgG2a/IgG1 anti-DNA antibodies ratio was also observed in animals injected with the WT Hsp65. Incubation of BALB/c macrophages with F(1) serum from WT treated mice resulted in acute cell necrosis; treatment of these cells with serum from K(409)A treated mice did not cause any toxic effect. Moreover, the involvement of WT correlates with age and is dose-dependent. Our data suggest that Hsp65 may be a central molecule intervening in the progression of the SLE, and that the point mutated K(409)A recombinant immunogenic molecule, that counteracts the deleterious effect of WT, may act mitigating and delaying the development of SLE in treated mice. This study gives new insights into the general biological role of Hsp and the significant impact of environmental factors during the pathogenesis of this autoimmune process.
Assuntos
Proteínas de Bactérias/uso terapêutico , Chaperoninas/uso terapêutico , Lúpus Eritematoso Sistêmico/prevenção & controle , Lúpus Eritematoso Sistêmico/fisiopatologia , Animais , Formação de Anticorpos , Chaperonina 60 , DNA/imunologia , Modelos Animais de Doenças , Progressão da Doença , Relação Dose-Resposta a Droga , Glomerulonefrite/etiologia , Glomerulonefrite/fisiopatologia , Lúpus Eritematoso Sistêmico/classificação , Camundongos , Mycobacterium lepraeRESUMO
The heat shock protein [Hsp] family guides several steps during protein synthesis, are abundant in prokaryotic and eukaryotic cells, and are highly conserved during evolution. The Hsp60 family is involved in assembly and transport of proteins, and is expressed at very high levels during autoimmunity or autoinflammatrory phenomena. Here, the pathophysiological role of the wild type [WT] and the point mutated K409 A recombinant Hsp65 of M. leprae in an animal mode of Systemic Lupus Erythematosus [SLE] was evaluated in vivo using the genetically homogeneous [NZBxNZW]F1 mice. Anti-DNA and anti-Hsp65 antibodies responsiveness was individually measured during the animal's life span, and the mean survival time [MST] was determined. The teatment with WT abbreviates the MST in 46%, when compared to non-treated mice [p<0.001]. An increase in the IgG2a/IgG1 anti-DNA antibodies ratio was also observed in animals injected with the WT Hsp65. Incubation of BALB/c macrophages with F1 serum from WT treated mice resulted in acute cell necrosis; treatment of these cells with serum from K409 A treated mice did not cause any toxic effect. Moreover, the involvement of WT correlates with age and is dose-dependent. Our data suggest that Hsp65 may be a central molecule, that counteracts the progression of the SLE, and that the point mutated K409 A recombinant immunogenic molecule, that counteracts the deleterious effect of WT, may act mitigating and delaying the development of SLE in treated mice. This study gives new insights into the general biological role of Hsp and the significant impact of environmental factors during the pathogenesis of this autoimmune process.
Assuntos
Animais , Camundongos , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/terapia , Relação Dose-Resposta a Droga , Células Procarióticas , Mycobacterium leprae/crescimento & desenvolvimento , Mycobacterium leprae/patogenicidadeAssuntos
Humanos , Adenocarcinoma Sebáceo/diagnóstico , Adenocarcinoma Sebáceo/fisiopatologia , Adenocarcinoma Sebáceo/reabilitação , Carcinoma/diagnóstico , Carcinoma/fisiopatologia , Carcinoma/reabilitação , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/reabilitação , Epiderme/anormalidades , Epiderme/fisiopatologia , Epiderme/lesões , Epidermodisplasia Verruciforme/diagnóstico , Epidermodisplasia Verruciforme/fisiopatologia , Epidermodisplasia Verruciforme/reabilitação , Fibroma Ossificante/diagnóstico , Fibroma Ossificante/fisiopatologia , Fibroma Ossificante/reabilitaçãoRESUMO
A new common idiotype, designated PR4, is described. This idiotype was originally identified on a human hybridoma-derived monoclonal antibody from a patient with leprosy, which binds the major Mycobacterium leprae-derived antigen, phenolic glycolipid-1, poly(ADP)-ribose, DNA, and poly(dT). The PR4 idiotype was found in patients with systemic lupus erythematosus (SLE) (70%), rheumatoid arthritis (40%), and Sjögren's syndrome (15%). It was not, however, found in the spouses of the SLE patients or (unlike other lupus idiotypes) in their healthy first-degree relatives. Although no correlation between PR4 idiotype levels and disease activity in SLE was found, a subset of rheumatoid arthritis patients with high levels of the idiotype was identified.