MICA and KIR: Immunogenetic Factors Influencing Left Ventricular Systolic Dysfunction and Digestive Clinical Form of Chronic Chagas Disease.

Christiane Maria Ayo,Luiz Carlos De Matttos,Luiz Sérgio Ronchi,Reinaldo Bulgarelli Bestetti,Eumildo De Campos Junior,Aldenis Albaneze Borim,Cinara Cássia Brandão

doi:10.3389/fimmu.2021.714766

Abstract

Tissue damage observed in the clinical forms of chronic symptomatic Chagas disease seems to have a close relationship with the intensity of the inflammatory process. The objective of this study was to investigate whether the MICA (MHC class I-related chain A) and KIR (killer cell immunoglobulin-like receptors) polymorphisms are associated with the cardiac and digestive clinical forms of chronic Chagas disease. Possible influence of these genes polymorphisms on the left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas heart disease was also evaluated. This study enrolled 185 patients with positive serology for Trypanosoma cruzi classified according to the clinical form of the disease: cardiac (n=107) and digestive (n=78). Subsequently, patients with the cardiac form of the disease were sub-classified as with LVSD (n=52) and without LVSD (n=55). A control group was formed of 110 healthy individuals. Genotyping was performed by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP). Statistical analyzes were carried out using the Chi-square test and odds ratio with 95% confidence interval was also calculated to evaluate the risk association. MICA-129 allele with high affinity for the NKG2D receptor was associated to the LVSD in patients with CCHD. The haplotype MICA*008~HLA-C*06 and the KIR2DS2-/KIR2DL2-/KIR2DL3+/C1+ combination were associated to the digestive clinical form of the disease. Our data showed that the MICA and KIR polymorphisms may exert a role in the LVSD of cardiac patients, and in digestive form of Chagas disease.

Highlights

Chagas disease, resulting from infection by the protozoan Trypanosoma cruzi, is a neglected disease that affects about 6-7 million people worldwide, especially in Latin America [1, 2]
The data obtained in this study provide evidence that broadens and reinforces our knowledge about the influence of the MICA and KIR genetic variants and their interactions with HLA class I molecules in the different clinical forms of chronic Chagas disease
MICA-129 allele with high affinity for the NKG2D receptor was associated to the left ventricular systolic dysfunction (LVSD)

Summary

Introduction

Chagas disease, resulting from infection by the protozoan Trypanosoma cruzi, is a neglected disease that affects about 6-7 million people worldwide, especially in Latin America [1, 2]. The acute phase of Chagas disease is usually asymptomatic; when symptomatic, symptoms usually are mild and unspecific [2]. About 60–70% of these individuals will never present clinical manifestation in the chronic phase, and the only evidence of the disease is positive serology (the so-called indeterminate form of chronic Chagas disease) [1]. Chronically infected individuals may develop clinical manifestations of this disease with irreversible lesions of some organs. After 20 years of infection, about 30% develop chronic Chagas heart disease (CCHD), which is clinically manifested by ventricular arrhythmia [3], thromboembolism [1], sudden cardiac death [1], chronic heart failure [1] and precordial chest pain with normal coronary arteries [4]. Ten per cent of Chagas patients present the digestive form of the disease, characterized mainly by dilatations of the esophagus and/or colon [5], cardio-digestive form or, less common, neurological alterations [2]

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