Heterophile Antibodies Heterophile antibodies are composed of a broad class of antibodies. These antibodies are stimulated by one antigen and react with an entirely unrelated surface antigen present on cells from different mammalian species. Heterophile antibodies may be present in normal individuals in low concentrations (titers), but a titer of 1:56 or greater is clinically significant in patients with suspected infectious mononucleosis.

The immunoglobulin M (IgM) type of heterophile antibody usually appears during the acute phase of infectious mononucleosis, but the antigen that stimulates its production remains unknown. IgM heterophile antibody is characterized by the following features:

• Reacts with horse, ox, and sheep erythrocytes

• Absorbed by beef erythrocytes

• Not absorbed by guinea pig kidney cells

• Does not react with EBV-specific antigens

Paul and Bunnell first associated infectious mononucleosis with sheep cell agglutination and developed a test for the infectious mononucleosis heterophile. Davidsohn modified the original Paul-Bunnell test, introducing a differential adsorption aspect to remove the cross-reacting Forssman and serum sickness heterophile antibodies. Rapid agglutination slide tests are now available.

Epstein-Barr Virus Serology

Within the adult population, 10% to 20% of individuals with acute infectious mononucleosis do not produce infectious mononucleosis heterophile antibody. The pediatric population is of particular concern because more than 50% of children younger than 4 years with infectious mononucleosis are heterophile negative. In diagnostically inconclusive cases of infectious mononucleosis, a more definitive assessment of immune status may be obtained through an EBV serologic panel. Candidates for EBV serology include those who do not exhibit classic symptoms of infectious mononucleosis, who are heterophile negative, or who are immunosuppressed.

Epstein-Barr–infected B lymphocytes express a variety of new antigens encoded by the virus. Infection with EBV results in the expression of viral capsid antigen (VCA), early antigen (EA), and nuclear antigen (NA), with corresponding antibody responses. Assays for IgM and IgG antibodies to these EBV antigens are available. EBV-specific serologic studies are beneficial in defining immune status, and their time of appearance may indicate the stage of disease (Fig. 1; Table 1). This can provide important information for the diagnosis and management of EBV-associated disease.

Fig1. Epstein-Barr virus (EBV) antibody response during the course of infectious mononucleosis. EA, Early antigen; VCA, viral capsid  antigen; EBNA, Epstein-Barr nuclear antigen; CF, complement fixation test. (Redrawn from Krugman S, et al: Infectious diseases of children, ed 9, St Louis, 1992, Mosby.)

Table1. Characteristic Antibody Formation in Infectious Mononucleosis

Patients with nasopharyngeal carcinoma have elevated titers of IgA antibodies to EBV replicative antigens, including VCA. These antibodies, which frequently precede the appearance of the tumor, serve as a prognostic indicator of remission and relapse.

Viral Capsid Antigen (VCA)

 VCA is produced by infected B cells and can be found in the cytoplasm. Anti-VCA IgM is usually detectable early in the course of infection, but is low in concentration and disappears within 2 to 4 months. Anti-VCA IgG is usually detectable within 4 to 7 days after the onset of signs and symptoms and persists for an extended period, perhaps lifelong.

Early Antigen (EA)

EA is a complex of two components, early antigen–diffuse (EA-D), which is found in the nucleus and cytoplasm of the B cells, and early antigen–restricted (EA-R), usually found as a mass only in the cytoplasm.

Anti–EA-D of the IgG type is highly indicative of acute infection, but it is not detectable in 10% to 20% of patients with infectious mononucleosis. EA-D disappears in about 3 months; however, a rise in titer is demonstrated during reactivation of a latent EBV infection.

Anti–EA-R IgG is not usually found in young adults during the acute phase but may be seen in the serum of very young children during the acute phase. Anti–EA-R IgG appears transiently in the later, convalescent phase. In general, anti–EA-D and anti–EA-R IgG are not consistent indicators of the disease stage.

Epstein-Barr Nuclear Antigen (EBNA) EBNA is found in the nucleus of all EBV-infected cells. Although the synthesis of NA precedes EA synthesis during the infection of B cells, EBNA does not become available for antibody stimulation until after the incubation period of infectious mononucleosis, when activated T lymphocytes destroy the EBV genome–carrying B cells. As a result, antibodies to NA are absent or barely detectable during acute infectious mononucleosis.

Anti-EBNA IgG does not appear until a patient has entered the convalescent period. EBNA antibodies are almost always present in sera containing IgG antibodies to VCA of EBV unless the patient is in the early acute phase of infectious mononucleosis. Patients with severe immunologic defects or immunosuppressive disease may not have EBNA antibodies, even if antibodies to VCA are present.

Under normal conditions, antibody titers to NA gradually increase through convalescence and reach a plateau 3 to 12 months after infection. The antibody titer remains at a moder ate, measurable level indefinitely because of the persistent viral carrier state established after primary EBV infection. Most healthy individuals with previous exposure to EBV have anti body titers to EBNA that range from 1:10 to 1:160. In EBV associated malignancies, the levels of EBNA antibody are usually high in patients with nasopharyngeal carcinoma and can range from barely detectable to very high levels in patients with Burkitt’s lymphoma.

Test results of antibodies to EBNA should be evaluated in relation to patient symptoms, clinical history, and antibody response patterns to VCA and EA to establish a diagnosis (Table 2). The antibody profile can be especially useful. For example, a patient with an infectious mononucleosis–like ill ness caused by reactivation of a persistent EBV infection resulting from an immunosuppressive malignancy or nonmalignant disease can demonstrate high titers of IgM and IgG VCA antibodies. If the antibody to EBNA is also elevated, however, a diagnosis of primary EBV infection can be excluded.

Table2. Characteristic Diagnostic Profile of Epstein-Barr Virus

Additional Testing

 Immunofluorescence is a common methology in EBV serology testing. Antigen substrate slides containing EBV-infected B cells are incubated with the patient’s serum. The presence of specific antibody is detected by the addition of fluorescein conjugated antihuman IgG or IgM. The disadvantages of this type of testing are that it is time-consuming, difficult to interpret, and prone to interference from other serum com ponents (e.g., rheumatoid factor).

The enzyme-linked immunosorbent assay (ELISA) may be used to detect antibodies to EBNA. This ELISA uses a synthetic peptide antigen to determine the relative amounts of IgM and IgG antibodies in patient serum or plasma. Its sensitivity is reportedly 98.9%, with a specificity of 99.0%.

اخر الاخبار

اخبار العتبة العباسية المقدسة

المجمع العلمي يجري اختباره الشهري لطلبة الحفظ في المثنى

قسم الصناعات: اعتماد أعلى معايير الجودة في التنجيد والتأثيث لدعم البنية الخدمية في العتبة المقدسة

قسم الشؤون الفكريّة يصدر الجزء الخامس من سلسلة دراسات في المنهج

جامعة الكفيل تنظّم دورة عن أساسيات الدفاع المدني لملاكاتها

المزيد

الآخبار الصحية

العنب.. فاكهة صغيرة بمفعول "خارق" للقلب والدماغ

دراسة تحدد "الحلقة المفقودة".. تسبب ارتفاع ضغط الدم

هذه الأطعمة تحمي دماغك من الشيخوخة وتزيد حدة الذكاء

خبراء يحذرون من مخاطر "الدهون المخفية" على القلب

المزيد

الآخبار التكنلوجية

الأرصاد الجوية تلجأ إلى الذكاء الاصطناعي.. لأي غرض؟

في منزلك.. "تعديل بسيط" يخفض ضغط الدم بشكل طبيعي

"ميزة جديدة" من إنستغرام تنافس تيك توك.. طال انتظارها

غوغل في مأزق.. بيانات 2.5 مليار مستخدم بقبضة القراصنة

المزيد

مواضيع ذات صلة

Peripheral Lymphoid Organs

Central Lymphoid Organs

Effector Functions of Complement

Complement Pathways

Mechanisms of innate immunity

Immunologic Manifestations of Viral, Rickettsial, and Mycoplasmal Diseases

Immunologic Manifestations of Fungal Diseases

The Structure of Antibodies

Myelomas and Monoclonal Antibodies

Telling the Difference Between Foreign and Self

The Basic Adaptive Immune Response

The Immunoglobulin Domain and Variations