Infectious mononucleosis (IM)
is characterized by
symptoms which are thought to be caused by -either
directly or indirectly-the expansion of CD3+CD8+T-cells after acute Epstein-Barr virus-infection resulting in a
decreased CD4/CD8 ratio. Over 50% of the T-lymphocytes response may be
EBVspecific [1,2]. Several viral infections (coxsackie B3, influenza,
parvovirus B19, varicella-zoster, cytomegalovirus) have been described
to be associated with cardiac complications, including pericarditis,
myocarditis and pericardial effusion [3-5]. However, there is not much
known about the involvement of cardiac complications in EBV-induced IM,
except for a few case studies. The study by Papadopoulou, et al.,
[6]in this issue of Indian Pediatrics for the first time sets out
to analyze the occurrence of cardiac complications in infectious
mononucleosis in a systematic manner. They evaluated 25 children
suffering from IM during the acute phase of infection and after 3-6
months for cardiac complications and relate these cardiac complications
to CD3+CD8+ T cell counts and CD4/CD8 ratio’s. As anticipated, the study
showed that CD3+CD8+ T-lymphocytes were increased and CD4/CD8 ratios
were decreased in all IM patients. Interestingly, echocardiography
revealed mild pericardial effusion in 13/25 patients, of which 12 had
very low CD4/CD8 ratios. In most patients all abnormal lymphocyte
populations returned to normal within 6 months as did any cardiac
complication. Interestingly, persistence of mild pericardial effusion
was seen in five patients. In these children CD3+CD8+ T cells were
elevated and CD4/CD8 ratios were decreased.
Although one of the difficulties in performing these
kind of studies lies in identifying symptomatic EBV-infections, as the
symptoms are mostly non-specific, the authors analyzed EBV
seroconversion data and performed T-cell phenotyping, making the
diagnosis of infectious mononucleosis more straightforward and therefore
patient selection was done properly. Although the authors did a great
job in performing this study and linking the cardiac complications to
T-cell counts, they could have discussed the mechanism behind the
occurrence of these cardiac complications better and include discussion
on other viruses which have previously been implicated in the context of
cardiac symptoms. The authors try to link the high T-cell numbers to the
cardiac complications, but state that this could be the result of high
load. Unfortunately, no attempt was made to actually measure the viral
load to elucidate this.
So the question remains whether cardiac complications
are caused by direct cytopathic actions of the virus or by
virus-initiated autoimmunity of the expanded T cells [7]. Seko, et al.,
[8] showed restricted usage of T-cell receptor Valpha-V beta genes
in infiltrating cells in the hearts of patients with acute myocarditis
and dilated cardio-myopathy, suggesting that an antigen-specific T-cell
subset plays a role. In addition, autoimmune effects are suggested as
the underlying mechanism for myocardial cellular destruction and
ventricular dysfunction in children following infection with varicella
zoster virus [8]. The involvement of T-cells was also implicated in an
experimental myocarditis model in mice after infection with influenza A
virus. It was shown that not the virus directly, but some function of
the host against viral evasion mediated myocarditis as it was abolished
by X-irradiation. As myocarditits did not develop in congenitally
athymic nude mice suggests that T-cells play a critical role in the
development of myocarditis [9]. As the EBV-specific T-cells at the acute
phase are characterized by lack of expression of CD27 indicative of high
effector function [10], it may well be that these T-cells are involved
in cardiac complications. Additional studies are required to prove this.
Although the context of the study by Papadopoulou,
et al was less clear and the link to autoimmunity effects could have
been discussed, at least their paper suggests that very low CD4/CD8
ratio may be taken as a surrogate marker for pericardial effusion and
increased CD3+CD8+ T-cells after 3 months are associated with
persistence of pericardial effusion and may thereby identify patients at
continuous risk. Additional analyses are required to establish cutoff
values of T-cell phenotypes for cardiac complications.
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