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Published on: August 1, 2014
CD45 is a more sensitive marker than CD3 to diagnose lymphocytic myocarditis in the endomyocardium
Linde Woudstra1, P Stefan Biesbroek2, Reindert W Emmens1
1Department of Pathology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands; ICaR-VU, Institute for Cardiovascular Research, VU University Medical Center, 1081 HV Amsterdam, the Netherlands.
Abstract:
To diagnose lymphocytic myocarditis (LM), immunohistopathological examination of endomyocardial biopsies (EMBs) is used with a cutoff value of at least 14 leukocytes per mm2, composed of CD3- and CD68-positive cells. We hypothesized that a more common leukocyte marker, CD45, instead of CD3 could increase the diagnostic sensitivity. Hearts of mice with acute viral myocarditis (n = 9) and of controls (n = 7) and the EMB sampling area of the left ventricular posterior wall (LVPW) obtained from autopsied hearts of patients diagnosed with LM (n = 18) and controls (n = 6) were stained with anti-CD68, anti-CD3, and anti-CD45. When applying the threshold of at least 14 leukocytes per mm2, 33% of the mice would be diagnosed with LM with the use of CD3+CD68 and 89% with the use of CD45+CD68. In the EMB sampling area of autopsied hearts, using the cutoff value of at least 14 leukocytes per mm2, CD3+CD68 could only confirm 17% of the diagnosis of LM, whereas CD45+CD68 could confirm 50% of the LM cases. Moreover, we compared inflammation in the EMB sampling area of the LVPW to the remaining myocardium of the LVPW and observed a significant increase of CD45+CD68 cells per mm2 in patients with LM. In conclusion, the use of the common leukocyte marker CD45 increases the sensitivity of the diagnosis of LM. Furthermore, the inflammatory infiltrate in the EMB sampling area is significantly increased compared with the remaining LVPW, indicating that the sampling area constitutes the highest chance for histological diagnosis of LM.
Insights
Using CD45, a common leukocyte marker, significantly improves the diagnosis of lymphocytic myocarditis (LM) in endomyocardial biopsies. This marker enhances sensitivity compared to CD3, aiding in accurate LM detection.
Area of Science:
- Cardiovascular Pathology
- Immunohistochemistry
- Myocarditis Research
Background:
- Lymphocytic myocarditis (LM) diagnosis relies on endomyocardial biopsies (EMBs) using CD3 and CD68 markers.
- Current diagnostic sensitivity for LM using EMBs may be limited.
Purpose of the Study:
- To evaluate if using CD45, a pan-leukocyte marker, enhances diagnostic sensitivity for LM compared to CD3.
- To compare inflammation in EMB sampling areas versus the general myocardium in LM patients.
Main Methods:
- Immunohistochemical staining of EMBs from mice and human autopsies using CD3, CD68, and CD45.
- Analysis of leukocyte counts (per mm²) in EMBs from LM patients and controls.
- Comparison of inflammation in the EMB sampling area versus the remaining myocardium.
Main Results:
- CD45+CD68 staining identified 89% of LM cases in mice, versus 33% with CD3+CD68.
- In human EMBs, CD45+CD68 confirmed 50% of LM diagnoses, compared to 17% with CD3+CD68.
- Significantly higher CD45+CD68 cell counts were observed in the EMB sampling area of LM patients' hearts.
Conclusions:
- CD45 is a more sensitive marker than CD3 for diagnosing LM in EMBs.
- The EMB sampling area shows increased inflammation, suggesting it's optimal for histological LM diagnosis.
