Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1996-04-29
1998-04-21
Woodward, Michael P.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435 693, 435 8, 435 91, 4351723, 436 63, G01N 3353, G01N 3348, C12P 2100, C12P 1934
Patent
active
057416567
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD OF INVENTION
This invention relates to a DNA sequence of the EBV genome coding for an EBV-related antigen that can be used in methods and diagnostic and pharmaceutical compositions referred to below and methods of localizing and isolating at least part of the respective DNA sequences. Furthermore, this invention relates to methods and compositions or kits, respectively, for a rapid, simple, very sensitive and highly specific determination of antibodies directed to this EBV-related antigen. In these tests said antigen of EBV essentially improves the detection of specific antibody classes in the patient sera. This detection allows reliable conclusions as to the status of infection of the donor such as preinfection, fresh infection, chronic infection, convalescence and neoplastic condition.
BACKGROUND ART
EBV causes infectious mononucleosis as a primary disease. Predominantly it affects children or young adults. More than 90% of the average adult population is infected by EBV that persists lifelong in its carriers. The virus is produced lifelong in the oropharynx and spreads via the oral route. Whereas infection of young children often leads to almost symptom free seroconversion, infection of adults often causes serious diseases with high fever, dramatic increases in white blood cell count, sore throat, enlarged liver and spleen. Scarlet fever, toxoplasmosis, diphteria and leukemia have to be discriminated by diagnostic means.
Rarely does EBV infection lead to chronic or chronically fluctuating symptoms comparable to the acute primary infection.
In immunocompromised patients EBV can cause serious lesions on the tongue.
Depression of cell mediated immunity leads to reactivation of EBV. Increased antibody titers are a consequence and detrimental effects of multiple possible sources such as transplant rejection have been described.
Certain genetic constellations are responsible for infection of male siblings leading to fatal lymphoreticular disease.
The development of Burkitt's lymphoma is linked to chromosomal rearrangements. Not all cases contain EBV genomes in the tumor cells. However, at least in areas with high incidence, 97% of these neoplasias are EBV-related and a control of EBV infection is likely to reduce the risk of developing Burkitt's lymphoma.
The other disease where EBV shows a 100% association is nasopharyngeal carcinoma (NPC) ("The Biology of Nasopharyngeal Carcinoma", UICC technical report series, vol. 71, M. J. Simons and K. Shanmugaratnam (eds), International Union Against Cancer, Geneva, p. 1 (1982)). NPC most frequently starts at the fossa of Rosenmueller (Recessus pharyngeus) at the postnasal space. Frequently patients are hospitalized only after the first typical metastases have developed in the cervical lymph nodes.
There are three possible basic strategies to control neoplasia:
These goals may be achieved also in multifactorial diseases such as many neoplasias. Incidence of disease may be reduced by eliminating one or more of the essential factors which are not necessarily capable by themselves to cause the disease, or by reducing factors which promote the manifestation of neoplastic conditions. The use of the specific virus-related antigens of this invention, antibodies or genetic materials as tools for early diagnosis of virus-related tumors, might facilitate the elimination of essential factors.
Before recombinant antigens with defined composition became available, the most common virus specific serological tests were based on immunofluorescence tests using EBV genome positive cells with various properties and/or pretreatment as source of usually cell-associated antigens in immunofluorescence or immunoenzymatic tests. Table I gives a summary of the antibody disease and vital antigens usable for diagnosis.
TABLE I ______________________________________
Correlation of EBV-caused diseases and Ig-subclass
specific antibody reaction as can be determined by
conventional immunofluorescence tests.
VCA EA EBNA MA.sup.1
Disease: IgG IgM IgA IgG IgG IgG
______
REFERENCES:
patent: 4683195 (1987-07-01), Mullis
Baer et al 1984 Nature 310 p. 207, Jul. 19, 1984.
Beisel et al. 1985 J Virology 54 (3) p. 665, Jun. 1, 1985.
Biggin et al 1984 EMBO 3 (5) p. 1083, May 1, 1984.
Motz Manfred
Reischl Udo
Wolf Hans Joachim
White John P.
Wolf Hans Joachim
Woodward Michael P.
Zeman Mary K.
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