MHC Class I and Class II Genes in Mexican Patients With Chagas Disease David Cruz-Robles, Pedro Antonio Reyes, Vı ´ctor Manuel Monteo ´ n-Padilla, Alda Rocı ´o Ortiz-Mun ˜ iz, and Gilberto Vargas-Alarco ´n ABSTRACT: Chagas’ disease contributes significantly to cardiovascular morbidity and mortality in several Latin- American countries. Previous studies have reported the effect of the human leukocyte antigen (HLA) molecules in the immune response regulation of Trypanosoma cruzi in- fection, and the association of HLA antigens with heart damage. We studied the major histocompatibility com- plex (MHC) class I (HLA-A and HLA-B), and class II (HLA-DR) genes in a sample of 66 serologically positive individuals with and without cardiomyopathy, and in 127 healthy controls. The total group of seropositive individ- uals revealed increased frequencies of HLA-B39 (p c = 4.310 -5 , odds ratio [OR] = 3.35) and DR4 (p c = 1.810 -5 , OR = 2.91) when compared to healthy con- trols. Increased frequencies of HLA-A68 and HLA-B39 were found in asymptomatic individuals when compared to patients with cardiomyopathy (p c = 0.014, OR = 4.99 and p c = 0.001, OR = 4.46, respectively). Also, patients with cardiomyopathy exhibited increased frequency of HLA-B35 when compared to healthy controls (p c = 0.048, OR = 2.56). The HLA-DR16 frequency was in- creased in patients with cardiomyopathy compared with asymptomatic individuals (p c = 0.05, OR = No deter- mined) and healthy controls (p c = 0.02, OR = 5.0). The results suggest that MHC alleles might be associated with the development of chronic infection and with heart dam- age in Chagas’ disease. HLA-DR4 and HLA-B39 could be associated directly with the infection by T. cruzi, whereas, HLA-DR16 could be marker of susceptibility to heart damage and HLA-A68 might confer protection to develop cardiomyopathy. Human Immunology 65, 60 – 65 (2004). © American Society for Histocompatibility and Immu- nogenetics, 2004. Published by Elsevier Inc. KEYWORDS: autoimmunity; cardiomyopathy; Chagas disease; genetic susceptibility; HLA alleles ABBREVIATIONS HLA human leukocyte antigens MHC major histocompatibility complex PCR-SSO polymerase chain reaction–sequence- specific oligonucleotide INTRODUCTION The American trypanosomiasis is caused by an intracel- lular protozoan Trypanosoma cruzi, and is the most com- mon cause of congestive heart failure and sudden death in Latin America [1]. From seroepidemiologic studies, the World Health Organization (WHO) estimates as many as 15 to 20 million people are infected in Latin America, and more than 65 million individuals are at risk of infection [2, 3]. The clinical manifestations of Chagas’ disease include an acute, and a chronic phase [4]. The acute phase is usually asymptomatic or runs a mild febrile course that subsides within a few weeks, but meningoencephalitis and severe myocarditis may occa- sionally occur and cause severe disease, even mortality in youngsters. Then a chronic phase develops. Most indi- viduals may remain asymptomatic for life, having circu- lating antibodies against T. cruzi (latent or indeterminate phase). Nearly 30% of infected individual develop the conspicuous cardiac and/or digestive manifestations after 10 to 20 years postinfection. Severe heart disorders, rhythm or conduction abnormalities, or a specific dilated cardiomyopathy generally lead to death. Some develop mega syndromes of the esophagus, colon, or other hollow organs [5]. From the Department of Pathology (D.C-R), Physiology Department (G.V-A), Immunoparasitology Laboratory (V.M.M-P), and Research Di- rection (P.A.R), Instituto Nacional de Cardiologı ´a “Ignacio Cha ´vez,”, Me´xico D.F.; and Doctorate Program in Biological Sciences (D.C-R), and Health Sciences Department (A.R.O-M), Universidad Auto ´noma Metropoli- tana-Iztapalapa, Me ´xico D.F., Me ´xico. Address reprint requests to: Dr. Gilberto Vargas-Alarco ´n, Department of Physiology, Instituto Nacional de Cardiologı ´a “Ignacio Cha ´vez,” Juan Badiano No. 1, Tlalpan 14080, Mexico D.F.; Tel: +52 (5) 573-29-11, ext. 1278; Fax: +52 (5) 573-09-26; E-mail: gvargas63@yahoo.com. Received June 10, 2003; revised October 10, 2003; accepted October 17, 2003. Human Immunology 65, 60 – 65 (2004) © American Society for Histocompatibility and Immunogenetics, 2004 0198-8859/04/$–see front matter Published by Elsevier Inc. doi:10.1016/j.humimm.2003.10.008