Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2012, vol. 21, nr 4, July-August, p. 455–467

Publication type: original article

Language: English

IgM Antibodies Against Apoptotic Cells and Phosphorylcholine in Patients with Acute Myocardial Infarction in Relation to Infarct Size and Inflammatory Response

Przeciwciała IgM przeciwko komórkom apoptotycznym i fosforylocholinie u chorych z ostrym zawałem serca w stosunku do rozmiaru zawału i reakcji zapalnej

Gwen M.P. Diepenhorst1,2,, Caroline L.F. Ciurana1,, Niubel Diaz Padilla1,, S. Matthijs Boekholdt3,, Paul A.J. Krijnen4,5,, Wim K. Lagrand4,6,, Hans W.M. Niessen4,5,, C. Erik Hack4,7,

1 Department of Immunopathology, Sanquin Research, Amsterdam, Netherlands

2 Department of Surgery (Surgical Laboratory), Academic Medical Center, Netherlands

3 Department of Cardiology, Academic Medical Center, Amsterdam, Netherlands

4 ICaR-VU, VU Medical Center, Amsterdam, Netherlands

5 Department of Pathology, VU Medical Center, Amsterdam, Netherlands

6 Department of Cardiology, VU Medical Center, Amsterdam, Netherlands

7 Department of Immunology, Rheumatology and Dermatology, University Medical Center, Utrecht, Netherlands

Abstract

Background. Natural IgM antibodies, and anti-phosphorylcholine IgM (anti-PC IgM) in particular, may modulate the pathogenesis of acute myocardial infarction (AMI).
Objectives. An exploratory study was conducted to evaluate the hypothesis that circulating anti-PC IgM and IgM binding to damaged cells increases the infarct size and post-infarct inflammatory response in patients with AMI.
Material and Methods. Plasma IgM binding to apoptotic cells (anti-apop IgM) and anti-PC IgM levels were compared in plasma samples from 50 patients with AMI and 46 healthy controls after correction for hemodilution. The cumulative release of cardiac markers LDH (lactate dehydrogenase), CK or CK-MB in human myocardium at 48 hours was used as an indication of infarct size. The circulating levels of mediators such as activated complement, C-reactive protein (CRP), interleukin-6 (IL6), interleukin-8 (IL8) and secretory phospholipase A2 (sPLA2) were used to assess the post-infarct inflammatory response. Patients with low (< median) and high (> median) levels of anti-apop IgM or anti-PC IgM were compared regarding infarct size and post-infarct inflammatory response. An electrocardiographical scoring system (Selvester score) was used to asses myocardial infarct size in patients with a first AMI (n = 24).
Results. AMI patients demonstrated lower levels of anti-PC IgM on admission (p < 0.01) and at 48 hours (p < 0.001) when compared to the healthy controls, whereas anti-apop IgM levels were comparable to control levels. In patients with a first infarct, patients with levels of anti-PC IgM above the median demonstrated larger electrocardiographic infarct sizes (p = 0.04) and a more pronounced response of the acute phase protein sPLA2 (p = 0.06), with a similar post-infarct course of LDH, CK and CK-MB.
Conclusion. These findings suggest that anti-PC IgM plasma levels may participatie in amplifying the inflammatory response of the ischemic heart and contribute to infarct size. However, the levels of anti-PC IgM in patients with AMI in this study do not show a significant effect on cardiac markers LDH, CK and CK-MB. Hence, conclusive evidence is not provided by this limited cohort.

Streszczenie

Wprowadzenie. Naturalne przeciwciała IgM, a zwłaszcza przeciwciała IgM przeciw fosforylocholinie (anty-PC IgM), mogą modulować patogenezę ostrego zawału serca (AMI).
Cel pracy. Poszukiwawcze badanie przeprowadzono w celu oceny hipotezy, że krążące anty-PC IgM i IgM wiążące do uszkodzonych komórek zwiększają rozmiar zawału i reakcję zapalną po zawale u chorych z AMI.
Materiał i metody. Stężenie przeciwciał IgM wiążące dla komórek apoptotycznych (anty-APOP IgM) oraz przeciwciał anty-PC w osoczu porównywano w próbkach od 50 pacjentów z ostrym zawałem serca oraz 46 zdrowych po korekcji hemodylucji. Skumulowane uwalnianie markerów sercowych LDH, CK lub CK-MB w ludzkim mięśniu sercowym po 48 godzinach wykorzystano do oceny wielkości zawału. Stężenie krążących mediatorów, takich jak: aktywowany dopełniacz, białko C-reaktywne (CRP), interleukina-6 (IL6), interleukina-8 (IL8) i wydzielnicza fosfolipaza A2 (sPLA2), wykorzystano do oceny reakcji zapalnej po zawale. Pacjentów z małym (< mediany) i dużym (> mediany) stężeniem anty-APOP IgM lub anty-PC IgM porównano pod względem rozmiaru zawału i odpowiedzi zapalnej po zawale. Oceniono wielkość zawału mięśnia sercowego u pacjentów z pierwszym zawałem serca (n = 24) za pomocą systemu punktacji (punktacja Selvester).
Wyniki. U pacjentów z AMI wykazano mniejsze stężenie IgM anty-PC przy przyjęciu (p < 0,01) i po 48 godzinach (p < 0,001) w porównaniu z osobami zdrowymi, a stężenie anty-APOP IgM było porównywalne do stężeń z grupy kontrolnej. Wśród pacjentów z pierwszym zawałem pacjenci ze stężeniem IgM anty-PC powyżej mediany mieli zawał większych rozmiarów (p = 0,04) i bardziej wyrazistą reakcję białka ostrej fazy sPLA2 (p = 0,06) oraz podobny przebieg LDH, CK i CK-MB po zawale.
Wnioski. Te odkrycia sugerują, że stężenie anty-PC IgM w osoczu może wzmocnić reakcję zapalną w chorobie niedokrwiennej serca i wpłynąć na rozmiar zawału. Stężenie IgM anty-PC u pacjentów z AMI w tym badaniu nie wykazało jednak znaczącego wpływu na markery sercowe LDH, CK i CK-MB. Dlatego badanie prowadzone na ograniczonej liczbie pacjentów nie dało jednoznacznych dowodów.

Key words

apoptosis, complement, cardiology, immunoglobulins, inflammation

Słowa kluczowe

apoptoza, dopełniacz, kardiologia, immunoglobuliny, zapalenie

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