Transfer of immune components from rabbit autoimmune cardiomyopathy into severe combined immunodeficiency (SCID) mice induces cardiomyopathic changes

Abstract

Transfer of IgG and PBL from rabbits immunized with combined beta1 and M2 peptides was able to reproduce the early stage of cardiomyopathic changes in SCID mice.

Role of β1-adrenoceptor autoantibodies in the pathogenesis of dilated cardiomyopathy

“…These autoantibodies, which are usually detectable in 30-40% of patients with DCM, often in coexistence with ␤ 1 -AABs, appeared functionally active both in vitro and in vivo in the cardiovascular system (Matsui et al 1997(Matsui et al , 2006. Immunization of rabbits with M 2 peptides was able to raise specific immune reactions and induce myocardial damage, similar to histological findings in human DCM (Matsui et al 1997).…”

“…The ␤ 1 -AABs also appeared to have more cardiotoxic effects than M 2 -muscarinic-AABs. Thus, in rabbits immunized with peptides corresponding to the sequence of the second extracellular loop of the ␤ 1 -AR (␤ 1 -peptide) or to the sequences of the M 2 -muscarinic receptor (M 2 peptide) the myocardial injury after immunization with both peptides was relatively mild in comparison with the more severe myocardial damage observed after immunization with the ␤ 1 -peptide alone (Matsui et al 2006). …”

“…Several of these cardiac-specific autoantibodies, such as ␣-myosin AABs, ␤1-adrenoreceptor AABs (␤1-AABs) and cardiac troponin I AABs, showed relevant pathologic potential (Konstadoulakis et al 1993;Lauer et al 2000Lauer et al , 1993Gavin et al 2002;Matsui et al 2006;Jahns et al 2004). Anti-␣-myosin AABs showed cross-reactions with bacterial (streptococcus group A) and viral (Coackievirus B3) proteins and have also been found in animal models of myocarditis created by immunizing mice with ␣-myosin (Cunningham et al 1986;Alvarez et al 1987;Gavin et al 2002).…”

“…Several authors have shown a high prevalence of autoantibodies against the human M 2 muscarinic acetylcholine receptor in DCM patients Matsui et al 2006;Yoshikawa et al 2009). These autoantibodies, which are usually detectable in 30-40% of patients with DCM, often in coexistence with ␤ 1 -AABs, appeared functionally active both in vitro and in vivo in the cardiovascular system (Matsui et al 1997(Matsui et al , 2006.…”

Acute Myocarditis – A Trigger of Cardiac Autoimmunity? Expected Insights from the Etiology, Titre-Course, and Effect on Survival of Cardiac Autoantibodies (ETiCS) Study

“…In addition to established anti-adrenergic drugs like cardioselective beta-blockers such strategies might comprise (a) the aforementioned epitope-derived peptides as antibodyscavengers (Jahns et al, 2010), (b) an elimination of functionally active cardiac aabs by selective or non-selective immunoadsorption (studies currently under way (Felix & Staudt, 2008;Müller et al, 2008)), or (c) the direct targeting/suppression of autoantibody-producing B cells and/or plasma-cells themselves (Neubert et al, 2008). At least in animal models of antibody-induced immune-cardiomyopathy and -nephropathy some of these novel therapeutic approaches have already been successfully applied (Jahns et al, 2005;Matsui et al, 2006;Neubert et al, 2008;Jahns et al, 2010). Hence, the results from the clinical (diagnostic) ETiCS study might also furnish a basis for and accelerate further pre-clinical development of such novel therapeutic approaches and agents targeting at cardio-noxious aabs, and -hopefully-for a faster transfer into clinical practice.…”