Negative Monospot, Positive Serology: What are the Implications?

December 31, 2006

Under what circumstances would the result of a monospottest be negative, while results of an Epstein-Barr virus(EBV) early antigen and a virus capsid antigen IgG testare positive?

Under what circumstances would the result of a monospottest be negative, while results of an Epstein-Barr virus(EBV) early antigen and a virus capsid antigen IgG testare positive? Would this be a false-negative?
-- April Wells, MSN, RN-CS
  &nbsp Gallipolis, Ohio
Acute EBV infection elicits specific cell- andantibody-mediated immune responses. Inmost patients, the immune response is sufficientto preclude the development of any illness.However, in adolescents and youngadults, it is common for infection to result in the clinicalsyndrome known as infectious mononucleosis (IM).There are other causes of IM, but EBV is the major one.The presence in the serum of antibodies to the EBVproteins known as the "early" or "viral capsid" antigensconstitutes solid proof that an infection has occurred.However, a positive serologic test for these antiviral antibodiesdoes not indicate when the infection occurred.Decades before EBV was found to be the majorcause of IM, hematologists identified a different kind ofreactivity in the sera of patients with IM--the so-calledheterophil antibodies. These are antibodies against antigensfound on the surfaces of animal red blood cells.They are not directed at any components of EBV itself; instead,they result from EBV's nonspecific global stimulationof antibody generation. Such heterophil reactions areseen in most patients with IM, and the monospot test andits many variants detect these heterophil antibodies. However,responses to other viruses or parasites--and evendrug reactions--can also stimulate production of heterophilantibodies. Thus, the monospot test is an indirectmarker for recent EBV-associated IM; only the EBV serologictests are specific for the infection. Finally, few personswith EBV infection actually have a positive result ona monospot test; those who do are primarily patients withongoing IM.
-- Stephen E. Straus, MD
  &nbspChief, Laboratory of Clinical Investigation
  &nbspNational Institute of Allergy and Infectious Diseases
  &nbspNational Institutes of Health
  &nbspBethesda, Md