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Epstein-Barr (EBV), Comprehensive Serology Profile

Epstein-Barr virus (EBV) is a herpesvirus with double-stranded DNA enclosed by proteins. The envelope of the virus has glycoproteins, which are important for attachment and entry into the host cells (B cells and epithelial cells). EBV targets B cells by utilizing their molecular machinery to replicate the viral genome. The virus causes B cells to differentiate into memory B cells, which then can move into the circulatory system, or become latent until a trigger causes reactivation.

The transmission of the Epstein-Barr virus occurs in several ways, such as deep kissing or food-sharing. Increased levels of viral DNA are found in salivary secretions after the initial infection. Children can be infected after eating food that has already been contaminated by an EBV-infected individual. The transmission can also occur through stem cell and organ transplantation, as well as blood transfusion.

Nearly 95% of the world’s population of adults over 40 years have been infected with the Epstein-Barr virus. The prevalence of seropositive subjects increased as age increased, except for in the infant population. Infants had elevated levels of Epstein-Barr virus IgG antibodies that decreased as they aged, likely due to loss of maternal antibodies over time.

Infection with Epstein Barr virus can cause a variety of symptoms, ranging from asymptomatic to a spectrum of illnesses. In children, infection with the Epstein-Barr virus can often be asymptomatic or present with vague symptoms. Patients infected with the Epstein-Barr virus can have systemic manifestations including splenomegaly, lymphadenopathy, headache, malaise, fever, and sore throat. Patients may show symptoms for several months, with fatigue as the most common lingering complaint. Lab abnormalities such as lymphocytosis, with the presence of atypical lymphocytes, are the most common. Liver function tests can also be abnormally elevated.

Determining if a patient has an infection due to the Epstein-Barr virus is usually most effective through serological testing. Heterophile antibody tests identify IgM antibodies against EBV. Heterophile antibody testing is a good initial test since it is inexpensive, fast, and has a sensitivity of 63-84% and specificity of 84 to 100%. The disadvantages of the heterophile antibody test include the possibility of a negative result in children since they may not produce heterophile antibodies to EBV. Unfortunately, other disease processes can induce heterophile antibodies, or they may be present for over a year, causing a positive result unrelated to an acute EBV infection. Viral capsid antigen (VCA) IgM and IgG can be used to confirm the diagnosis. Elevated levels of VCA IgM antibodies detect an acute infection, while increased VCA IgG antibody levels indicate prior or chronic infection.

Several other diseases need to be considered as part of the differential diagnosis. Bacterial pharyngitis presents with a sore throat, cervical lymphadenopathy, pharyngeal swelling, and tonsillar exudates. Viral pharyngitis usually includes fatigue, fever, rhinorrhea, or conjunctivitis. Cytomegalovirus (CMV) is another virus in the Herpesviridae family that presents similarly to EBV with a sore throat, fevers, chills, elevated liver function tests, and fatigue. Splenomegaly and lymphadenopathy are less common CMV symptoms. Acute HIV infection is also on the differential. These patients present with fevers, muscle and joint pain, fatigue, headaches, and sometimes with lymphadenopathy and pharyngitis.

Epstein-Barr virus has several associated complications. One dangerous complication is splenic rupture due to infectious mononucleosis. Another complication of infectious mononucleosis from EBV is airway obstruction from tonsillar edema of the pharyngeal tissues. Acute acalculous cholecystitis is a complication that can be treated conservatively with pain medication and antiemetics. There are many other complications from Epstein-Barr virus infection that can occur, such as myocarditis, encephalitis, hemophagocytic lymphohistiocytosis, pancreatitis, and autoimmune hemolytic anemia. EBV has also been implicated in causing lymphomas and nasopharyngeal cancers.

The antibodies against the Epstein-Barr virus are four: IgM and IgG VCA (against Viral Capsid Antigen), IgG EA (against Early Antigen), and IgG EBNA (Against Nuclear Antigen). Measurement of these antibodies is useful in distinguishing recent primary infection, acute infection, reactivation, and past inactive infection.

Negative - - - -
Acute + + +/- -
Recent + +/- +/- +/-
Past + - - +
Reactivation + +/- + +
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