Association of Heart Failure in Homozygous β-Thalassemia With the Major Histocompatibility Complex

Abstract

Background —In β-thalassemia major, heart failure primarily affecting left ventricular systolic function is the most common complication and cause of death. Apart from iron deposition, it has been recently reported that myocarditis might be another contributing factor in the pathogenesis of acute or chronic heart failure, acting possibly through an autoimmune mechanism. In an attempt to assess the role of immunogenetic factors in the development of heart failure associated with β-thalassemia major, we studied the frequency of major histocompatibility antigens/alleles A, B, DR, and DQ in homozygous β-thalassemic patients with and without heart failure primarily affecting the left ventricle. Methods and Results —Forty-five consecutive unrelated Greek patients with homozygous β-thalassemia and left-sided chronic heart failure were studied. Fifty-eight unrelated Greek patients with homozygous β-thalassemia without heart failure and 130 unrelated Greek healthy controls were also studied. In all subjects, class I HLA-A and -B typing was performed by the complement-mediated lymphocytotoxicity assay, whereas class II HLA-DR and -DQ typing was performed by polymerase chain reaction. HLA-DRB1*1401 allele frequency was significantly increased in patients with β-thalassemia major without left-sided heart failure compared with those with heart failure (corrected P [ P c ]=0.02, odds ratio 0.1) and healthy controls ( P c =0.001). HLA-DQA1*0501 allele frequency was increased in patients with heart failure compared with patients without heart failure ( P c =0.04, odds ratio 14) and healthy controls ( P c =0.004). Conclusions —Differences exist in the immunogenetic profile between homozygous β-thalassemic patients with and without left-sided heart failure, raising the possibility that genetically defined immune mechanisms may play an important role in the pathogenesis of heart failure in β-thalassemia.

Associated Complications In Beta Thalassemia Patients

“…It is responsible for more than half of the deaths [12,13].It may take the form of cardiomyopathy, pulmonary hypertension, heart failure, arrhythmias, pericarditis and myocarditis. Although iron overload is the main cause but other factors; genetic, immune or infective, may also be important [14]. Hepatic complications were found to be less significant complications and our results (6.8%) were in accordance with earlier studies [15,16].…”

Cardiac iron and cardiac disease in males and females with transfusion-dependent thalassemia major: a T2* magnetic resonance imaging study

“…Nutritional deficiencies, including selenium, thiamine, vitamin D and carnitine, and thyroid disease have been reported to cause heart dysfunction in thalassemia. Finally, genetically determined variables could affect susceptibility to heart dysfunction in the presence of iron overload 18 and a consistent percentage of our patients showed a heterogeneous myocardial iron burden.…”

Pengaruh Kadar Feritin Serum terhadap Fungsi Ventrikel Kiri pada Thalassemia Mayor yang Mendapat Transfusi Multipel

“…Hal ini mungkin karena umur pada sampel penelitian oleh Ali pada anak yang lebih tua, remaja dan dewasa muda. Dibandingkan dengan hasil feritin serum pada penelitian oleh Bosi G dkk 14 1280, Vaccari M dkk 15 1131 dan Kremastinos DT dkk 16 2220, maka hasil pada penelitian ini masih lebih tinggi. Keadaan feritin serum yang tinggi ini mungkin karena 50% dari subjek penelitian pada awalnya tidak memperoleh terapi dengan desferal secara teratur.…”