KIR genes, their HLA ligands and MICA gene polymorphism in ocular toxoplasmosis and in digestive form of Chagas disease

Abstract

The toxoplasmosis and Chagas disease are caused by parasitic protozoa T.gondii and T. cruzi, respectively. While toxoplasmosis is clinically manifested in the forms of the eye, brain and congenital Chagas disease after a period of approximately two decades without symptoms, manifests itself in chronic one-third of individuals. The clinical manifestations of this disease include chronic irreversible lesions in some organs and approximately 30% of patients develop chronic Chagas heart disease and 10% in the gastrointestinal tract (magaesôfago and / or megacolon). The progression of an infection and the development of different clinical forms and different degrees of severity, can be related to the genetic characteristics of the pathogen and the host. Among the host factors, the immune response arouses special interest, and the genetic markers play an important modulatory role in this context, since several studies have reported the importance of immune response genes in resistance or susceptibility to disease. The overall goal of this project is to test the hypothesis that genes KIR (killer cell immunoglobulin-like receptors) and MICA (major histocompatibility complex class I-related chain A) are associated with ocular toxoplasmosis and digestive form of Chagas disease. Specific objectives include: 1. Select two groups of patients with toxoplasmosis Like this: TO-1 Group - exudative lesion and / or scar corioretiniana; Group TO-2 - no exudative lesions and / or scar corioretiana, and select two groups of patients with disease Chronic Chagas Like this: CH-1 group - patients with gastrointestinal clinical form of Chagas disease (megaesophagus and megacolon), Group-CH 2 - individuals with the cardiac form, mixed or asymptomatic with positive serology for Chagas disease. 2nd. Verifying the presence of anti-T. gondii and T. cruzi IgM and IgG in the serum of these patients, as indicators of acute or chronic infection, 3. Identifying the KIR genes, HLA class I (HLA-A, HLA-B and HLA-C), binders KIR, and MICA gene polymorphism in all groups of patients, 4. Checking whether these genes are associated with the development of ocular toxoplasmosis and digestive form of Chagas disease. Results will be analyzed using the Arlequin program version 3.1 to determine the Hardy-Weinberg equilibrium and the allele frequencies of HLA gene and haplotype and MICA. The KIR gene frequency is obtained by direct counting. The comparison between the groups will be done in 2x2 contingency table using the chi-square test with Yates correction or Fisher exact test. Odds ratio and confidence interval of 95% are calculated to verify the estimates of association using the program OpenEpi version 2.3.1. Our hypothesis is that MICA and KIR genes are associated with ocular toxoplasmosis and digestive form of Chagas disease. (AU)