Epstein-Barr VirusEpstein-Barr VirusTerry Kotrla, MS, MT(ASCP)BBTerry Kotrla, MS, MT(ASCP)BB

DiseasesDiseases African or Burkitt’s LymphomaAfrican or Burkitt’s Lymphoma

– malignant B-cell neoplasm malignant B-cell neoplasm – presents as a rapidly growing tumour of presents as a rapidly growing tumour of

the jaw, face or eyethe jaw, face or eye– grows very quickly, and without grows very quickly, and without

treatment most children die within a few treatment most children die within a few months months

– Epstein-Barr virus (EBV) has been Epstein-Barr virus (EBV) has been strongly implicated strongly implicated

African or Burkitt’s LymphomaAfrican or Burkitt’s Lymphoma

Although BL is a very rapidly growing tumour Although BL is a very rapidly growing tumour it responds well to treatment. it responds well to treatment.

Three pictures: before treatment, 3 days and Three pictures: before treatment, 3 days and 6 days after treatment6 days after treatment

Nasopharyngeal CarcinomaNasopharyngeal Carcinoma Endemic in South China, Africa, Arctic Endemic in South China, Africa, Arctic

EskimosEskimos This is a malignant tumour of the squamous This is a malignant tumour of the squamous

epithelium of the nasopharynx.epithelium of the nasopharynx. 100% contain EBV DNA100% contain EBV DNA Rates are less than 1 per 100,000 in most Rates are less than 1 per 100,000 in most

populations populations Nasopharyngeal carcinomas are found in Nasopharyngeal carcinomas are found in

association with reactivation of latent association with reactivation of latent Epstein-Barr Virus.  Epstein-Barr Virus. 

The exact mechanisms of association are The exact mechanisms of association are unknown unknown

B-Cell LymphomaB-Cell Lymphoma In most individuals infected with In most individuals infected with EBVEBV, the , the

virus is present in the virus is present in the BB-cells, which are -cells, which are normally controlled by T-lymphocytes normally controlled by T-lymphocytes

When T-When T-cellcell deficiency exists, one clone of deficiency exists, one clone of EBVEBV-infected -infected BB-lymphocytes escapes -lymphocytes escapes immune surveillance to become immune surveillance to become autonomously proliferating. autonomously proliferating.

EBVEBV induced induced B cellB cell lymphomas are most lymphomas are most prevalent in immunocompromised prevalent in immunocompromised patients. patients.

Oral Hairy Cell LeukoplakiaOral Hairy Cell Leukoplakia Viral infection of the oral cavity. Viral infection of the oral cavity. Indicator of HIV infection as well as of a Indicator of HIV infection as well as of a

person's lessening or weakening immunityperson's lessening or weakening immunity

Infectious MononucleosisInfectious Mononucleosis Downey cells may be presentDowney cells may be present

Heterophile Heterophile Antigens/AntibodiesAntigens/Antibodies

An antigen or antigenic determinant An antigen or antigenic determinant which is found in different tissues in which is found in different tissues in more than one species. more than one species.

These are antibodies found in one These are antibodies found in one specie of animal (such as humans) specie of animal (such as humans) which react against a component of which react against a component of another specie.another specie.

Paul Bunnell TestPaul Bunnell Test The original Paul-Bunnell test was a simple titration of The original Paul-Bunnell test was a simple titration of

sheep cell agglutinins but this procedure was subsequently sheep cell agglutinins but this procedure was subsequently modified in order to distinguish between sheep cell modified in order to distinguish between sheep cell agglutinins formed in IM and the Forssman-type antibodies agglutinins formed in IM and the Forssman-type antibodies found in normal serum, serum sickness and in certain other found in normal serum, serum sickness and in certain other conditions.conditions.

Tissues rich in Forssman antigen (guinea pig kidney) absorb Tissues rich in Forssman antigen (guinea pig kidney) absorb Forssman antibodies but do not affect the heterophil Forssman antibodies but do not affect the heterophil antibodies in IM.antibodies in IM.

Heterophil antibodies are absorbed by beef cells,Heterophil antibodies are absorbed by beef cells, Forssman hapten is a glycolipid usually associated with a Forssman hapten is a glycolipid usually associated with a

protein, the determinant being largely carbohydrate and protein, the determinant being largely carbohydrate and therefore heat stable.therefore heat stable.

Davidsohn DifferentialDavidsohn Differential The principle behind the Paul-Bunnell-Davidsohn test is that The principle behind the Paul-Bunnell-Davidsohn test is that

the two types of sheep agglutinins are distinguished by the two types of sheep agglutinins are distinguished by titrating them before and after absorption with guinea pig titrating them before and after absorption with guinea pig kidney and ox cells.kidney and ox cells.

Patients serum containing antibodies due to IM is added to Patients serum containing antibodies due to IM is added to guinea pig kidney cells. These antibodies are not absorbed guinea pig kidney cells. These antibodies are not absorbed by the kidney cells. These antibodies then react with Beef by the kidney cells. These antibodies then react with Beef (Ox) red blood cells which causes agglutination and is a (Ox) red blood cells which causes agglutination and is a positive test for IM.positive test for IM.

Patients serum containing Forssman antibodies are added Patients serum containing Forssman antibodies are added to guinea pig kidney cells. Antibodies are absorbed by the to guinea pig kidney cells. Antibodies are absorbed by the kidney cells. These antibodies are then allowed to react kidney cells. These antibodies are then allowed to react with Beef red blood cells which does not cause with Beef red blood cells which does not cause agglutination. This is a positive test for Forssman antigens.agglutination. This is a positive test for Forssman antigens.

Davidsohn DifferentialDavidsohn Differential** To be considered absorbed there must be greater than a three tube To be considered absorbed there must be greater than a three tube

difference between the presumptive titer and the differential titer.difference between the presumptive titer and the differential titer.

Heterophil Antibody ------------------------ Infectious Mono

Kidney Extract ------------------ Not Absorbed

Beef Erythrocyte --------------------- Absorbed

Forssman

Absorbed

Not Absorbed

Serum Sickness

Absorbed

Absorbed

Davidsohn DifferentialDavidsohn DifferentialAdvantagesAdvantages

When properly performed, When properly performed, this test is specific for this test is specific for Infectious Mononucleosis Infectious Mononucleosis and false-positive results and false-positive results are rare.are rare.

DisadvantagesDisadvantages

Davidsohn Differential test Davidsohn Differential test is very time consuming is very time consuming and burdensome.and burdensome.