Elsevier

Clinica Chimica Acta

Volume 408, Issues 1–2, 1 October 2009, Pages 114-122
Clinica Chimica Acta

Invited critical review
Detection of antibodies in cardiac autoimmunity

https://doi.org/10.1016/j.cca.2009.08.002Get rights and content

Abstract

Cardiac autoimmunity has been widely studied over the last years. A lot of cardiac antigens have been identified. Laboratory tests for detection of antibodies against the heart are very helpful in diagnosing and monitoring cardiac autoimmune diseases, but the prevalence of anti-heart antibodies varies a lot between the tests. The aim of this paper is to review the number of laboratory assays used today and to determine the most suitable test for detection of cardiac autoantibodies in human serum.

Introduction

Several different heart conditions have an autoimmune origin. Cardiac autoimmunity is often caused by molecular mimicry. Following infection, certain microbial antigens can mimic cardiac self-antigens and activate normally resting autoreactive T cells [1], [2], [3], [4], [5], [6], [7], [8]. Another cause of autoimmunity against the heart is tissue damage following cardiac surgery or myocardial infarction, which can provoke the release of cellular proteins. This release of self-antigens after cellular damage, activates dendritic cells and can break immunotolerance [9]. These proteins may function as autoantigens leading to the formation of anti-heart antibodies (AHA) [10]. Since the 1950s, many researches are carried out on AHA. The prevalence of AHA varies a lot between those studies, because of the different detection techniques. Today, the detection of AHA is mainly based on indirect immunofluorescence (IIF) [11], [12], [13]. For more detailed analysis of AHA, other techniques are needed.

The purpose of this review is to give an overview of the different types of AHA and to compare the techniques that are used to detect these antibodies in human serum. Also the clinical use of cardiac autoantibody detection is described in this article. Finally a conclusion is made about which laboratory test is preferable in detection of cardiac autoantibodies.

Section snippets

Anti-heart antibodies

In the past, AHA were detected by passive agglutination with human heart extract, tanned red cell technique on non-human myocardium, antiglobulin consumption test, precipitin tests, complement fixation and immunofluorescence techniques (IIF) [14], [15], [16]. The used heart antigens were not well defined and the different procedures caused a great diversity in AHA. These techniques are abandoned today, except for IIF, which is still used today [11], [12], [13].

Further heterogeneity of anti-heart antibodies

Detailed biochemical analysis reveals that AHA are specific antibodies against mitochondrial, sarcolemmal, structural, intracellular and contractile proteins, and against receptors of the cardiomyocyte.

The chief structural components of the myofibrillar apparatus of cardiomyocytes are the contractile proteins actin, myosin, troponin and tropomyosin. Actin [10], [17], [18], [19], [20], [21] and especially myosin [10], [12], [17], [18], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29]

Indirect immunofluorescence

Indirect immunofluorescence for detection of AHA, is based on binding of fluorescein-labeled antibodies, directed against the AHA. IIF uses heart tissue sections from primate, human or rodent origin, as antigenic source. The sections are incubated with patient sera resulting in one or more patterns of immunofluorescence staining [62], [63]. A sarcolemmal or myolemmal pattern is seen when antibodies against membrane proteins and intercellular proteins of the heart are present. A

Comparison of the detection techniques

IIF and SDS-PAGE followed by Western blotting are both techniques that are capable of identifying a variety of cardiac autoantigens recognized by autoantibodies; this makes them suitable as screening tools. But IIF has a lot of disadvantages: the technique is not automated, is semi-quantitative, time-consuming and requires experienced personnel. IIF is also difficult to interpret because in some studies, healthy persons were also positive for AHA. These are mostly at lower levels, but IIF is

Cardiac autoimmunity following trauma

Late pericarditis following myocardial infarction, cardiac surgery, or trauma is respectively referred to as postmyocardial infarction syndrome (PMIS) or postcardiotomy syndrome (PCS). Together, these syndromes are classified as ‘post-cardiac injury syndromes’ (PCIS). PCIS is characterized by pleuritic chest pain, elevated ESR, abnormal chest X-ray, and the presence of exudative pericardial and/or pleural effusions [62]. The pathogenesis of PCIS is not fully understood yet. The most widely

Conclusions

A lot of people suffer from cardiac disease as a result of cardiac autoimmunity. In many cases, antibodies against self-antigens of the heart are detectable in an early stage of the disease.

Laboratory tests for detection of cardiac autoantibodies can be helpful in diagnosing cardiac autoimmune diseases, predicting disease outcome, assessing the need for immunotherapy, and gaining insight into disease pathogenesis. There is evidence that a decline in antibody titers during therapy, predicts a

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