Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome, 1995, Sairenji et al

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Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome

T Sairenji, K Yamanishi, Y Tachibana, G Bertoni, T Kurata

Abstract
To test for an association between chronic fatigue syndrome (CFS) and infections with Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7), antibodies to these viruses were tested in the serum from three groups of individuals: (1) 10 CFS patients with chronic fatigue beginning with a clinical pattern of acute infectious mononucleosis [IM; true chronic IM (CIM)]; (2) 10 CFS patients whose illness did not start with acute IM (non-CIM), and (3) healthy controls. High EBV antibody titers were demonstrated in most patients. Antibodies to ZEBRA, a product of the immediate early EBV gene BZLF1, were detected in the serum of CFS patients at a higher frequency than in healthy controls. Antibody titers to HHV-6 and HHV-7 were also higher in the patients with CFS than in the controls. These results are consistent with the view that CFS patients may have reactivations of EBV, HHV-6 and HHV-7.

Link (Intervirology) [Paywall]

 

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Criteria is 1988 Holmes.

All 20 patients met the working case definition of CFS of the United States Centers for Disease Control. The 10 patients with CIM had been well until experiencing IM, characterized by the classic clinical picture accompanied by either atypical lymphocytosis, heterophile antibody, or both. All patients with CFS had been ill for at least 2 years prior to serum collection. Sera from healthy adults, aged 20-40 years old, the staff of laboratories at the National Institute of Health, Tokyo, Japan and the University of Massachusetts Medical School, Worcester, Mass.. USA were obtained as controls.

This paper is interesting because it looked at 10 people with ME/CFS whose illness was immediately preceded by an acute infectious mononucleosis (EBV) infection (CIM group), 10 whose did not (non-CIM), and 26 healthy controls. Both ME/CFS groups had higher antibody titers to EBV than controls, but somewhat surprisingly, the group whose illness began with EBV did not have higher titers than the other ME/CFS group.

These are the antibody titers to different parts of EBV. For the first column, VCA, the black dots are anti-VCA IgG, the open dots are anti-VCA IgM. The anti-VCA IgG titers are the most striking difference between ME/CFS and controls.


From CDC about these EBV antibodies:

Viral capsid antigen (VCA)
Anti-VCA IgM appears early in EBV infection and usually disappears within four to six weeks.

Anti-VCA IgG appears in the acute phase of EBV infection, peaks at 2 to 4 weeks after onset, declines slightly then persists for the rest of a person's life.

Early antigen (EA)
Anti-EA IgG appears in the acute phase of illness and generally falls to undetectable levels after three to six months. In many people, detection of antibody to EA is a sign of active infection. However, 20% of healthy people may have antibodies against EA for years.

EBV nuclear antigen (EBNA)
Antibody to EBNA (determined by the standard immunofluorescent test) is not seen in the acute phase of EBV infection. Instead, it slowly appears 2 to 4 months after onset of symptoms and persists for the rest of a person’s life. Other EBNA enzyme immunoassays may report false positive results.

Antibody titers to two different strains of HHV-6 type A, a strain of HHV-6 type B, and HHV-7 were also higher in both ME/CFS groups than controls, but not different between the two ME/CFS groups.


Quote discussing EBV

The finding that CFS patients had high antibody titers to EBV, HHV-6 and HHV-7 indicates that CFS might be associated with these viral infections. It was expected that CIM would have high antibody titers to EBV — patients with acute IM caused by a primary EBV infection evolve to CIM patients with a CFS pattern. Prolonged EBV infection may continue in some patients after acute IM, as EBV reactivation or CIM.

However, our results demonstrated that high EBV titers were observed not only in CIM but also in non-CIM. This finding is consistent with the conclusion that non-CIM individuals also have reactivated EBV infection.

Since anti-VCA IgM antibody was detected in only 2 CFS patients at a low titer (1:5), EBV infection in these patients can be considered to be from EBV reactivation rather than from a primary, recent infection.

Quote discussing HHV

Serum of CFS patients and controls was also tested by indirect immunofluorescence for antibodies to HHV-6 type A (strains GS and U1102) and type B (fig. lb). Sero-positivity (≥ 1:10) was higher in patients with CIM and non-CIM than in controls. Most CFS patients had elevated antibody titers to HHV-6. The GMTs of antibodies to each of the two A strains and to the B strain were all significantly higher in CFS patients than in controls (p < 0.05). The antibody titers to the different HHV-6 strains were similar in each individual (data not shown).

Anti-bodies to HHV-7 strain RK were also tested in the serum of CFS patients and controls (fig. lb). Seropositivity was observed in 20 of 20 (100%) and 23 of 26 (88%) CFS and control sera, respectively. The GMT of this response in CFS patients was higher than for controls (p < 0.03). No difference was observed in the titers between CIM and non-CIM subgroups of CFS patients.