Antibodies to the Epstein-Barr virus in serum

From the serological methods of diagnosing the disease, the most common is the Paul-Bunnel( agglutination) reaction, aimed at detecting heterophilic AT in the serum. The titer of heterophilic AT 1: 224 and higher in the serum of the patient is recognized as diagnostically significant, confirming the diagnosis of infectious mononucleosis. Heterophilic agglutination is positive in 60% of young people after 2 weeks and in 90% after 4 weeks from the onset of clinical manifestations of the disease. Therefore, several studies are needed to diagnose infectious mononucleosis: during the first week of the disease( the reaction may be negative) and 1-2 weeks later( the reaction may become positive).

The content of heterophilic antibodies decreases after the end of the acute period of the infectious process, but their titer can be determined within 9 months after the onset of clinical symptoms. The Paul-Bunnel reaction can turn from positive to negative, even against the background of residual hematological and clinical symptoms in the patient. Sensitivity of the method in adults is 98%, specificity is 99%.In children with infectious mononucleosis at the age of 2 years, heterophilic antibodies are detected only in 30% of patients, at the age of 2-4 years - in 75%, over 4 years - in more than 90%.

The sensitivity of the method in children is less than 70%, the specificity is 20%.Reduction, and then repeated increase in the titer of heterophilic antibodies can occur in response to another infection( most often in viral infections of the upper respiratory tract).The Paul-Bunnel response is not specific for the Epstein-Barr virus. The titer of heterophilic AT does not give a cross reaction and does not correlate with specific AT to the Epstein-Barr virus, nor does it correlate with the severity of the disease course. The test is useless for diagnosing the chronic form of infectious mononucleosis( positive on average only in 10% of patients).

Titers 1:56 or less can be found in healthy people and in patients with other diseases( rheumatoid arthritis, rubella).False positive test results are met very rarely.

At present, the method of "single spot"( slide agglutination) is used to determine AT for erythrocytes of a ram, it is used initially as a screening test. By sensitivity, it is comparable to the Paul-Bunnel reaction. False-positive slide tests can be approximately 2% of studies( in leukemia, malignant lymphoma, malaria, rubella, viral hepatitis, pancreatic carcinoma), and false-negative in adults - in 5-7% of cases.

It should be noted that the spectrum of diagnostic test systems produced by firms based on the determination of AT titer is very wide, therefore it is necessary to focus on the diagnostic AT titer specified in the instruction manual for test systems.

If heterophilic antibodies are not detected, and the clinical picture of the disease corresponds to infectious mononucleosis, it is necessary to examine serum for specific AT classes IgM and IgG.For the detection of specific antibodies to the Epstein-Barr virus, indirect immunofluorescence methods are used( they can detect AT to EA and VCA Ar), antikomplement-immunofluorescence( detect AT to EA, VCA and EBNA Ar) and ELISA.

AT to EA Ag D component( anti-EA-D) appear even in the latent period of the primary infection and quickly disappear with recovery.

AT to EA Ag component( anti-EA-R) can be detected 3-4 weeks after clinical manifestations of the disease. They persist in the blood serum for about a year, often detected with atypical or protracted currents of infectious mononucleosis. Usually these ATs are found with Burkitt's lymphoma.

AT to VCA class IgM( anti-VCA IgM) appear very early, usually to clinical symptoms, they are detected at the onset of the disease in 100% of cases. High titers occur on the 1-6th week from the onset of infection, they begin to decrease from the 3rd week and usually disappear after 1-6 months. Anti-VCA IgM is almost always present in the serum with active infection, so the method of their detection is very sensitive and specific for an acute episode of infectious mononucleosis.

AT to VCA class IgG( anti-VCA IgG) may appear early( in the 1-4 weeks), their number peaks to the 2nd month of the disease. At the onset of the disease, they are found in 100% of cases. Only 20% of patients showed a 4-fold increase in the titer in the study of paired sera. The titre decreases on recovery, but is found within several years after the transferred infection, therefore it is useless for the diagnosis of infectious mononucleosis. The presence of anti-VCA IgG indicates a state after infection and immunity.

AT to EBNA( anti-EBNA) appear later than all, rarely present in the acute phase of the disease. Their content increases during the recovery period( within 3-12 months), they can persist in the blood for many years after the disease. The lack of anti-EBNA in the presence of anti-VCA IgM and anti-EA IgM indicates a current infection. The detection of anti-EBNA after a previously negative reaction indicates an existing infection. When using the ELISA method, it is possible to simultaneously detect the presence of anti-EBNA classes of IgM and IgG.If the amount of anti-EBNA IgM is greater than the anti-EBNA IgG, an acute infection should be considered, with the reverse relationship being the previous one.

In favor of an acute primary infection, one or more of the following symptoms indicates the presence of

?anti-VCA IgG( detected early, and later the content is reduced);

?High titer( more than 1: 320) or 4-fold increase in the titre of anti-VCA IgG during the course of the disease;

?a transient rise in the titer of anti-EA-D( 1:10 or more);

?early anti-VCA IgG without anti-EBNA, and later - the emergence of anti-EBNA.

Acute or primary infection caused by the Epstein-Barr virus is excluded if the anti-VCA IgG and anti-EBNA titers in the serum do not change when tested in dynamics( acute period and recovery).

The persistent presence of early Ag and anti-VCA IgG in high titers indicates a chronic phase of infection.

In Table.profiles of serological tests in different stages of infectious mononucleosis are presented.

Detection of AT to Epstein-Barr virus is used to diagnose infectious mononucleosis and chronic infections caused by the Epstein-Barr virus.

AT to Epstein-Barr virus can be detected in the following diseases: secondary immunodeficiency states, including HIV infection, nasopharyngeal carcinoma, Burkitt's lymphoma, CMV infection, syphilis, Lyme disease, brucellosis, etc.

Since infectious mononucleosis -systemic lymphoproliferative disease, which develops under the influence of a number of etiological agents, it is very important to correctly build a survey tactics for such patients. In Fig.the algorithm of using serological tests in patients with symptoms of acute mononucleosis is given.

Fig. An algorithm for examining patients with suspected infectious mononucleosis.