Autoimmune Mechanisms as the Basis for Human Peripartum Cardiomyopathy

Abstract

The etiology and mechanisms of pathogenesis of human peripartum cardiomyopathy (PPCM) remain unknown. The incidence and prevalence of this disease is rare in some parts of the world and more common in others. The purpose of this review is to summarize our current knowledge of the factors that have been entertained which may contribute to the pathogenesis of PPCM with special emphasis on more recent data from our laboratory that provide support to the view that this disease is an autoimmune disease with multiple contributing factors and effector mechanisms. This is supported by the fact that sera from PPCM patients contain high titers of auto-antibodies against normal human cardiac tissue proteins of 37, 33, and 25 kD that was not present in the sera of patients with idiopathic cardiomyopathy (IDCM), indicating for the first time that PPCM is distinct from IDCM. In addition to the autoantibodies, the PBMC's from PPCM patients demonstrate a heightened level of fetal microchimerism, an abnormal cytokine profile, decreased levels of CD4+ CD25lo regulatory T cells, and a significant reduction in the plasma levels of progesterone, estradiol and relaxin in PPCM patients as compared with other normal pregnant non-PPCM patients. A potential role for reduced plasma levels of selenium in the pathogenesis of select PPCM patients was also noted. These findings for the first time suggest that such abnormalities may in concert lead to the initiation and perpetuation of an autoimmune process, which leads to cardiac failure and disease. Identification of the precise nature of the cardiac tissue autoantigens (currently in progress) will pave the way for the delineation of mechanism of this autoimmune disease. A working model for the pathogenesis of this disease is also described herein.

Peri-partum cardiomayopathy-not a rare entity, clinical profile in a rural tertiary care center in Gujarat, India

“…These include consuming lake salt or rock salt (Kanva) or heating of the body on a clay bed with fire beneath to keep warm. 15 Recent studies implicate the role of a prolactin sub fragment 16KDa which is cleaved from prolactin due to unbalanced oxidative stress. The 16KDa can destroy the endothelium and damage the micro circulation in the myocardium, reducing the cardiac function and causing ventricular dilatation.…”

“…13,14 Another phenomenon is fetal chimerism in which fetal cells are present in maternal circulation during and after delivery, which after delivery are recognized by maternal system as foreign antigens and may trigger an immune response. [13][14][15] Abnormal response to haemodynamic stress of pregnancy is a hypothesis which suggests that some alterations in the haemodynamic setup results in cardiac hypertrophy.…”

Pregnancy and heart disease: what Internists should know

“…A fetal cell, arriving in the cardiac tissue can stimulate a pathological maternal immunological response. 92,93 Supporting this hypothesis there are high titers of autoantibodies against normal human cardiac tissue proteins (including myosin), adenine nucleotide translocator, and branched-chain alpha-keto acid dehydrogenase 94 that have been described only in patients affected and not in controls. Instead there are conflicting results on immunoglobulins which resulted higher than control in one study 95 and identical to controls in another one.…”

Prevalence and Characteristics of Peripartum Cardiomyopathy among Women with Cadiac Failure Referred for Echocardiography in a Tertiary Hospital in Northern Nigeria

“…Peripartum cardiomyopathy is defined as dilated cardiomyopathy of uncertain origin that occurs in pregnant women from the last trimester to the postpartum period with no preexisting heart disease [12]. It is recognized as a separate entity because of its distinct epidemiologic characteristics, relatively rapid onset and association with unique auto antigens and autoantibodies [13].…”