Peripartum cardiomyopathy, an autoimmune manifestation of allograft rejection?
Introduction
Noted in the 18th century, pregnancy associated heart failure was first described in 1937 [1]. In the early 70s, at Chicago's Cook County Hospital, it was defined as peripartum cardiomyopathy (PPCM), characterized by cardiac decompensation in the last month of pregnancy or up to five months postpartum [2]. This definition has not much changed [3], [4], though PPCM is now believed also to occur earlier in pregnancy [5]. With “unknown” etiology, PPCM's current definition still includes absence of obviously determinable causes [3], [4].
Diagnoses are still frequently delayed and/or overlooked, as symptoms may mimic normal physiologic findings of pregnancy or be mistaken for preeclampsia/eclampsia [3]. Both conditions may present with congestive heart failure and/or pulmonary edema, but preeclampsia/eclampsia, in contrast to PPCM, is usually not characterized by left ventricular systolic dysfunction [6].
Section snippets
Etiology and pathophysiology
PPCM is amongst only a small number of conditions, characterized by first occurrence and recurrence in association with pregnancy. Amongst those, where an etiology is known, all are considered autoimmune conditions, and this kind of occurrence pattern has, therefore, been characterized as autoimmune [7]. It, therefore, does not surprise that PPCM has been suggested to represent an autoimmune disease [8], [9], [10], [11].
We, however, in subtle contrast, consider PPCM one (amongst many possible)
Autoimmunity in non-pregnancy associated cardiomyopathy
Outside of pregnancy, chronic myocarditis [22], [23] and especially idiopathic dilated cardiomyopathy [24], [25], [26], [27], [28], [29] have been associated with anti-cardiac autoimmune responses. As in cardiac transplantation, autoantibodies appear polyclonal, associated with cytokine abnormalities [27], [28] and can be organ-specific or not [29]. Some heart-specific autoantibodies are poorly defined [24], but most are anti-myosin antibodies [25], [26] and some exert functional effects on
PPCM's other characteristics of autoimmune conditions
Abnormal autoimmunity is familial and one autoimmune condition in an individual predisposes to the development of others [32]. Whether this applies to PPCM is unknown. PPCM, however, demonstrate a dramatically higher prevalence in African than Caucasians women [3], [4], suggesting a genetic component to risk, and in this sense behaves like an autoimmune condition.
After pregnancy, autoimmune diseases may go into remission, only to clinically resurface later. In contrast, autoimmune phenomena,
What speaks against it and why it matter?
Recent reports, implying that the hormone prolactin mediates PPCM [35], and that inhibition of prolaction may enhance recovery from PPCM [36] have been suggested to be contradictory to an autoimmune etiology for the condition. Such an opinion, however, ignores that elevated prolactin levels have been associated with abnormal autoimmune function in general [37], [38], specific autoimmune conditions, such as systemic lupus erythematousus, rheumatoid arthritis and thyroid disease and that
Take-home messages
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There is convincing circumstantial evidence in support of abnormal autoimmune function as an underlying pathophysiologic mechanism in the development of PPCM.
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It is, however, tempting to speculate further that these observed autoimmune responses are not representative of an autoimmune condition, but reflect the typically observed autoimmune components of malfunctions in allograft (in this case pregnancy-) tolerance.
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Building on this concept, pharmaceutical interventions, which have been proven
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Cited by (33)
Heart Failure With Reduced Ejection Fraction
2021, Sex Differences in Cardiac Diseases: Pathophysiology, Presentation, Diagnosis and ManagementFatal accelerated rejection with a prominent natural killer cell infiltrate in a heart transplant recipient with peripartum cardiomyopathy
2018, Transplant ImmunologyCitation Excerpt :Ischemia/reperfusion injury and viral pathogens can activate innate immunity, but no evidence supports either mechanism in this case. NK cells could mediate antibody-dependent cellular cytotoxicity in response to CD16-FcRγIIIA ligation [11] potentially triggered by alloantibodies and/or autoantibodies secondary to PPCM [17,18]. Interestingly, recipient genotyping of the killer Ig receptors (KIR) revealed the presence of activating KIR (2DS2, and 2DS3 of KIR B haplotypes), and 2DS4 with its cognate HLA-C1 and C2 ligands in the donor (Table 1).
Editorial: How do genetic components play a role in peripartum cardiomyopathy?
2015, Journal of Cardiology CasesClinical Outcomes for Peripartum Cardiomyopathy in North America: Results of the IPAC Study (Investigations of Pregnancy-Associated Cardiomyopathy)
2015, Journal of the American College of CardiologyPreventing congenital neonatal heart block in offspring of mothers with anti-SSA/Ro and SSB/La antibodies: A review of published literature and registered clinical trials
2013, Autoimmunity ReviewsCitation Excerpt :How a passively transferred SSA/Ro–SSB/La autoantibody-mediated immune response would cause such divergent tissue damage is somewhat difficult to imagine and has not been replicated in animal models. Autoimmune abnormalities, including autoantibody abnormalities, are fairly typically associated with allogeneic graft rejection and GVHD [34]. In solid allogeneic organ transplantation complications they, however, do not usually reflect causation.
Hyperplacentosis, autoimmunity and postpartum depression: Is there a link?
2013, Autoimmunity Reviews