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

• Published in: Circulation (New York, N.Y.) Vol. 100; no. 20; pp. 2074 - 2078
• Main Authors: Kremastinos, Dimitrios T., Flevari, Panagiota, Spyropoulou, Maria, Vrettou, Helen, Tsiapras, Dimitrios, Stavropoulos-Giokas, Catherine G.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 16.11.1999; American Heart Association, Inc
• Subjects: Adolescent; Adult; beta-Thalassemia - complications; Biological and medical sciences; Cardiology. Vascular system; Echocardiography; Female; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Histocompatibility Testing; Homozygote; Humans; Male; Medical sciences; Ventricular Dysfunction, Left - etiology; Human; Heart failure; Hemoglobinopathy; Hemolytic anemia; β-Thalassemia; Pathogenesis; Heart disease; Major histocompatibility system; Clinical form; Cardiovascular disease; Hemopathy; Genetic disease
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/01.CIR.100.20.2074

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.