Associação de HLA-DR2 com cardiopatia crônica em uma população da região noroeste do Estado do Paraná, Brasil

A doença de Chagas é um dos maiores problemas que afetam a saúde pública no Brasil e outros países latino americanos. No entanto, poucos trabalhos avaliaram a susceptibilidade genética a esta doença. Como genes de resposta imune estão localizados no Complexo de Histocompatibilidade HLA, decidimos estudar a associação entre os antígenos HLA e a forma cardíaca da doença de Chagas, que parece apresentar um componente auto-imune importante. Trinta e cinco pacientes e 72 controles residentes na região noroeste do estado do Paraná foram utilizados neste estudo. Métodos estatísticos clássicos foram usados para comparar as freqüências HLA entre pacientes e controles. Os dados confirmam uma associação primária com HLA-DR2 (48.4%vs12.3%; Pc=0,0011) e secundária com HLA-B7 (31.4%vs8.3%; Pc=0.033). Concluindo, uma associação positiva entre DR2 e cardiopatia chagásica crônica foi demonstrada numa população de brancos brasileiros, reforçando a hipótese do envolvimento de fatores genéticos na susceptibilidade à forma cardíaca da doença de Chaga

Action of the medicine Canova® on peritoneal resident macrophages infected with Trypanosoma cruzi = Ação do medicamento Canova® em macrófagos peritoniais residentes infectados por Trypanosoma cruzi

Approximately 20 million of people are chronically infected withTrypanosoma cruzi in Latin America. The present work investigated the action of the homeopathic medicine Canova® on in vitro experimental infections with T. cruzi Y strain, using Swiss mice resident peritoneal macrophages. Our results demonstrated that Canova®induced a decrease in the production of H2O2 and TNF-a at 20 and 40% concentrations when compared to the control RPMI. However, when compared with this medicine excipient, a significant decrease in these mediators was observed with Canova® at 40% concentration only. The production of NO and phagocytic activity were not affected. TNF-a inhibits T. cruzi replication in peritoneal macrophages in vitro, becoming an important agent of infection control by this parasite. Within this context, Canova®, unlike what has been reported with other infections, would function as a stimulator of the infection, since it inhibited the production of TNF-α by peritoneal resident macrophages in vitro. Further studies should be carried out with elicited macrophages, in order to confirm the inhibitoryactivity of Canova® on the production of TNF-α and other mediators in macrophages infected by T. cruzi.<br><br>Aproximadamente 20 milhões de pessoas são cronicamente infectadas pelo Trypanosoma cruzi na América Latina. O presente trabalhoinvestigou a ação do medicamento homeopático Canova® em infecções experimentais “in vitro” com Trypanosoma cruzi, cepa Y, usando macrófagos residentes peritoniais de camundongos Swiss. Os resultados indicaram que Canova® induz a diminuição significativa da produção de H2O2 e TNF-α em concentrações de 20 e 40%, quando comparado com ocontrole RPMI. Quando comparado com o excipiente do medicamento, observou-se diminuição na concentração destes mediadores apenas na concentração de 40%. A produção de NO e a atividade fagocítica não foram afetadas. TNF-α inibe a replicação do protozoário em macrófagos peritoniais “in vitro”, mostrando-se importante agente para o controle da infecção pelo parasita. Portanto, o medicamento Canova® poderia estimular o processo de infecção, pois promoveu inibição da produção de TNF-α por macrófagos peritoniais residentes “in vitro”. Estudos adicionais devem ser realizados com macrófagos elicitados, afim de confirmar a atividade inibitória da Canova® sobre a produção de TNF-α e outros mediadores em macrófagos infectados por T. cruzi

Action of the medicine Canova ® on peritoneal resident macrophages infected with

Trypanosoma cruz

Killer Cell Immunoglobulin-like Receptors and Their HLA Ligands are Related with the Immunopathology of Chagas Disease.

The aim of this study was to investigate the influence of killer cell immunoglobulin-like receptor (KIR) genes and their human leucocyte antigen (HLA) ligands in the susceptibility of chronic Chagas disease. This case-control study enrolled 131 serologically-diagnosed Chagas disease patients (59 men and 72 women, mean age of 60.4 ± 9.8 years) treated at the University Hospital of Londrina and the Chagas Disease Laboratory of the State University of Maringa. A control group was formed of 165 healthy individuals - spouses of patients or blood donors from the Regional Blood Bank in Maringa (84 men and 81 women, with a mean age of 59.0 ± 11.4 years). Genotyping of HLA and KIR was performed by PCR-SSOP. KIR2DS2-C1 in the absence of KIR2DL2 (KIR2DS2+/2DL2-/C1+) was more frequent in Chagas patients (P = 0.020; Pc = 0.040; OR = 2.14) and, in particular, those who manifested chronic chagasic cardiopathy-CCC (P = 0.0002; Pc = 0.0004; OR = 6.64; 95% CI = 2.30-18.60) when compared to the control group, and when CCC group was compared to the patients without heart involvement (P = 0.010; Pc = 0.020; OR = 3.97). The combination pair KIR2DS2+/2DL2-/KIR2DL3+/C1+ was also positively associated with chronic chagasic cardiopathy. KIR2DL2 and KIR2DS2 were related to immunopathogenesis in Chagas disease. The combination of KIR2DS2 activating receptor with C1 ligand, in the absence of KIR2DL2, may be related to a risk factor in the chronic Chagas disease and chronic chagasic cardiopathy

Distribution of <i>KIR</i> genes in healthy controls, chronic Chagas disease patients and in groups of patients with and without heart involvement.

<p>CCD: chronic Chagas disease patients, NC: without heart involvement patients, CCC: chronic chagasic cardiopathy patients.</p><p>^<b>a</b><i>P</i> = 0.017; <i>Pc</i> = 0.27; OR = 0.41; 95% CI = 0.20–0.83 (CCC vs Controls)</p><p>Distribution of <i>KIR</i> genes in healthy controls, chronic Chagas disease patients and in groups of patients with and without heart involvement.</p

Distribution of KIR and their respective HLA ligands in Chagas disease patients and controls.

<p>CCD: chronic Chagas disease patients; NC: without heart involvement patients, CCC: chronic chagasic cardiopathy patients.</p><p>^<b>a</b><i>P</i> = 0.036; <i>Pc</i> = 0.108; OR = 0.43; 95% CI = 0.24–0.75 (CCD vs Controls)</p><p>^<b>b</b><i>P</i> = 0.037; <i>Pc</i> = 0.10; OR = 0.54; 95% CI = 0.31–0.94 (CCD vs Controls)</p><p>^<b>c</b><i>P</i> = 0.031; <i>Pc</i> = 0.093; OR = 0.23; 95% CI = 0.04–0.89 (CCC vs NC)</p><p>Bw4 = <i>HLA-A*23</i>,<i>*24</i>,<i>*32; HLA-B</i>,<i>*13</i>,<i>*27</i>,<i>*44</i>,<i>*51</i>,<i>*52</i>,<i>*53</i>,<i>*57</i>,<i>*58</i></p><p>Group C1 = <i>HLA-C*01</i>,<i>*03</i>,<i>*07</i>,<i>*08</i>,<i>*12</i>,<i>*14</i>,<i>*16</i></p><p>Group C2 = <i>HLA-C*02</i>,<i>*04</i>,<i>*05</i>,<i>*06</i>,<i>*07</i>,<i>*15</i>,<i>*17</i>,<i>*18</i></p><p>Distribution of KIR and their respective HLA ligands in Chagas disease patients and controls.</p