RESUMO
The relationship between autoimmunity and malaria is not well understood. To determine whether autoimmune responses have a protective role during malaria, we studied the pattern of reactivity to plasmodial antigens of sera from 93 patients with 14 different autoimmune diseases (AID) who were not previously exposed to malaria. Sera from patients with 13 different AID reacted against Plasmodium falciparum by indirect fluorescent antibody test with frequencies varying from 33-100%. In addition, sera from 37 AID patients were tested for reactivity against Plasmodium yoelii 17XNL and the asexual blood stage forms of three different P. falciparum strains. In general, the frequency of reactive sera was higher against young trophozoites than schizonts (p < 0.05 for 2 strains), indicating that the antigenic determinants targeted by the tested AID sera might be more highly expressed by the former stage. The ability of monoclonal auto-antibodies (auto-Ab) to inhibit P. falciparum growth in vitro was also tested. Thirteen of the 18 monoclonal auto-Ab tested (72%), but none of the control monoclonal antibodies, inhibited parasite growth, in some cases by greater than 40%. We conclude that autoimmune responses mediated by auto-Ab may present anti-plasmodial activity.
Assuntos
Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Soros Imunes/imunologia , Plasmodium falciparum/imunologia , Anticorpos Monoclonais/imunologia , Doenças Autoimunes/sangue , Estudos de Casos e Controles , Reações Cruzadas , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Soros Imunes/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/crescimento & desenvolvimentoRESUMO
The relationship between autoimmunity and malaria is not well understood. To determine whether autoimmune responses have a protective role during malaria, we studied the pattern of reactivity to plasmodial antigens of sera from 93 patients with 14 different autoimmune diseases (AID) who were not previously exposed to malaria. Sera from patients with 13 different AID reacted against Plasmodium falciparum by indirect fluorescent antibody test with frequencies varying from 33-100 percent. In addition, sera from 37 AID patients were tested for reactivity against Plasmodium yoelii 17XNL and the asexual blood stage forms of three different P. falciparum strains. In general, the frequency of reactive sera was higher against young trophozoites than schizonts (p < 0.05 for 2 strains), indicating that the antigenic determinants targeted by the tested AID sera might be more highly expressed by the former stage. The ability of monoclonal auto-antibodies (auto-Ab) to inhibit P. falciparum growth in vitro was also tested. Thirteen of the 18 monoclonal auto-Ab tested (72 percent), but none of the control monoclonal antibodies, inhibited parasite growth, in some cases by greater than 40 percent. We conclude that autoimmune responses mediated by auto-Ab may present anti-plasmodial activity.
Assuntos
Humanos , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Soros Imunes/imunologia , Plasmodium falciparum/imunologia , Anticorpos Monoclonais/imunologia , Doenças Autoimunes/sangue , Estudos de Casos e Controles , Reações Cruzadas , Técnica Indireta de Fluorescência para Anticorpo , Soros Imunes , Plasmodium falciparum , Plasmodium falciparum/crescimento & desenvolvimentoRESUMO
The acquisition of protective immunity in malaria is a slow process during which autoantibodies are produced. The present work aimed at studying a possible interference of autoimmune responses on malaria immune protection. This was done by investigating the presence of autoantibodies in the sera of malarious patients, by searching for reactivity of autoantibodies from autoimmune patients against plasmodial antigens, and by studying the effect of such antibodies on the in vitro growth of Plasmodium falciparum. Sera from systemic lupus erythematosus (SLE) and malaria patients were tested against autologous and plasmodial antigens. Out of the 109 SLE sera tested, 48 (44%) reacted against the parasite. In addition, 26 (47%) out of 55 randomly selected sera, mainly those containing anti-DNA and antinuclear autoantibodies, were able to inhibit parasite growth to some extent. Conversely, a high frequency (81%) of sera of malaria patients exhibited reactivity against autoantigens. The results show that patients with autoimmune processes can produce antibodies that recognize plasmodial antigens in the absence of plasmodial infection, that malaria patients can produce autoantibodies, that SLE sera can inhibit plasmodial growth in vitro, and that the presence of anti-DNA and antinuclear antibodies may be important in such anti-plasmodial activity. It is concluded that autoimmune responses may have influence on the protective immunity against malaria.
Assuntos
Antígenos de Protozoários/imunologia , Autoanticorpos/imunologia , Soros Imunes/imunologia , Lúpus Eritematoso Sistêmico/sangue , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/imunologia , Animais , Antígenos de Protozoários/metabolismo , Autoanticorpos/farmacologia , Reações Cruzadas , Humanos , Soros Imunes/farmacologia , Lúpus Eritematoso Sistêmico/imunologia , Plasmodium falciparum/crescimento & desenvolvimentoRESUMO
Three recombinant proteins spanning the Plasmodium falciparum liver-stage Ag-3 (LSA-3) were used to immunize Aotus monkeys. The proteins were delivered subcutaneously without adjuvant, adsorbed onto polystyrene 0.5 microm particles at a concentration of 2 microg per immunization. Control animals received glutathione-S-transferase formulated similarly. Animals were challenged as late as 5 months after the last immunization, by intravenous inoculation of 100,000 P. falciparum sporozoites of a strain heterologous to the one from which the immunogens were derived. Sterile protection was achieved in three of the five immunized monkeys but in none of four controls. Antibodies were at low titer, but reacted with the native parasite protein and were boosted by parasite challenge. Ag-specific IFN-gamma secretion was detectable in all LSA-3-immunized animals in response to the LSA-3-derived Ag. The protection was apparently associated with high levels of IFN-gamma production in response to in vitro recall Ag. These results lend support to the vaccine potential of LSA-3 indicated by previous results obtained in chimpanzees, as well as the value of yet another Ag-delivery system. They also support the value of the Aotus model for the pre-clinical development of pre-erythrocytic-stage vaccines.