Search

Heterophile antibody levels for sheep and rat red cells were studied in White, Asian and Bantu blood donors in Durban, South Africa. The Bantu were found to have significantly higher heterophile antib

The significance of heterophile antibodies remains incompletely explained. There is considerable evidence that its mechanism is based upon a phenomenon that is kindred, if not identical, with that of specific antibody formation. Aside from certain infectious conditions, and also in infectious mononucleosis, its importance in clinical medicine is so far limited to serum sickness, which is definitely an allergic phenomenon. In a study of a fairly large number of allergic individuals, most of whom were symptom free at the time the blood was taken, as compared with a group of nonallergic controls, we found a higher incidence of heterophile antibody in the former group. However, when repeating the study with a group having allergic symptoms at the time the blood was taken, we found not only a lower frequency of high heterophile titers than in the first allergic group, but also a distinctly lower frequency than among the nonallergics. The evidence as presented may be interpreted in either of two ways: that there is no constant relationship between the allergic state, active or quiescent, and the heterophile antibody titer; or, that the possibility of a reduced titer during the acute allergic phase may be of significance and deserves further investigation. Against this latter possibility is the fact that in the acute allergic reaction of serum sickness others have found the titer to be increased. Our technique was unaltered in the study of the three groups, and the different results cannot be explained on technical inconsistencies. It is possible that the third group is too small to be of statistical significance. Our findings coincide with the observations of others, in that the history of serum administration frequently agrees with a high titer.

Decrease in heterophile antibody activity to cow, pig, and sheep red blood-cells was found in groups of patients with large-bowel and breast tumours irrespective of the extent and spread of the tumour or the length of known history. The significance of these observations is discussed in the light of known cancer-surveillance mechanisms. The findings may reflect decreased host immunological resistance to these tumours even in the early stage of their development, and the measurement of heterophile antibody activity may provide a useful and uncomplicated screening test.

The spinal fluid was studied in twenty cases of infectious mononucleosis proved by clinical picture, blood studies and serological examination. It may be concluded that in acute cases of infectious mononucleosis, the heterophile antibody does not pass into the spinal fluid, but that there may be an increase in cell count, particularly lymphocytes, and in protein content, which is not necessarily proportional to the cell count elevation. These findings have no correlation with central nervous system signs or symptoms.

ConclusionHeterophile antigen has a wide distribution in the various types of pneumococci. It is logical to assume, therefore, that heterophile antigen is at least part of the complex species-antigenic structure of most pneumococci.

A new rapid slide test for the detection of infectious mononucleosis heterophile antibody has been compared with the Paul-Bunnell absorption test. Out of 200 sera, 46 were seropositive for infectious mononucleosis by the Paul-Bunnell test and 43 of these were detected by the Monosticon test; the three Monosticon-negative sera were of low titre. There was no problem with false positive reactions due to heterophile antibody not specific for infectious mononucleosis.

Disease: Infectious mononucleosis (IM), Burkitt’s lymphoma (BL), undifferentiated nasopharyngeal carcinoma (NPC).

Infectious mononucleosis is a well described disorder, so there is no need for me to review the features of the classic syndrome or the extensive evidence for Epstein-Barr virus (EBV) as its major cause. I will, instead, review a number of selected aspects of infectious mononucleosis that have occupied my attention for the past few years, but which are incompletely addressed in the literature. These include the rather provocative issues of relapse, recurrence, and chronicity of EBV infection in the normal host.

The diagnosis of an acute episode of infectious mononucleosis (IM) is made on the basis of clinical symptoms and serological evidence for development of heterophile antibodies. In an effort to obtain a very sensitive and specific assay for diagnosis of IM, we have developed MERISTAR:IM. The MERISTAR assay uses latex beads coated with purified bovine heterophile antigen. We compared the sensitivity and specificity and performance characteristics of the latex-based test to those of the commercially available erythrocyte-based Monospot test with serum samples from 363 suspected-IM patients and controls. A total of 28 samples from patients with confirmed IM were positive with the MERISTAR assay, while only 23 of the samples were positive with the Monospot assay. The two assays had equal specificity, as each test gave two false-positive results. In the technical performance of the assay, the MERISTAR assay was simpler and faster to perform than the Monospot assay.

Ten rapid slide agglutination tests for infectious mononucleosis were evaluated. The quality of the technical information included with the kits was found to differ considerably, as did the composition of the tests and the principles of test specificity. Furthermore, large variation was found in the shelf life and price of the different kits. Thirty-nine serum samples were selected according to titre in the Paul-Bunnell-Davidsohn differential absorption test, largely from the low titre area, since this is where most diagnostic problems can be expected. The sera were tested blindly using the ten rapid slide agglutination tests. Considerable differences were found in specificity and sensitivity. When compared with the results obtained from PBD, the tests could be divided into two groups. The first group consisted of three kits, all of which gave false negative, but no false positive results. The remaining seven tests gave false negative and false positive results, but were more sensitive than the tests in the first group. The large variation in the results obtained when using the different kits under controlled conditions indicates that such tests may give even less satisfactory results in practice.

A small proportion of sera submitted for routine immunofluorescent antibody screening contains heterophile antibodies. The reaction patterns produced by the heterophile antibody may be confused with or mask specific autoantibody patterns, leading to false positive or false negative autoantibody results. In this study we report the development of a method in which fresh sheep red cells are used to absorb heterophile antibody from sera without affecting specific autoantibody which may be present. This technique was used on a panel of 142 sera known to contain heterophile antibody but not initially reported as containing specific autoantibodies by immunofluorescence. After absorption with sheep red cells the heterophile antibody was completely removed from the sera under test and 27 (19%) specimens were shown to contain previously undetected autoantibodies. Only 6 (4%) of the sera, however, contained autoantibodies at a titre which would be reported as a positive result on routine screening. These results suggest that there may be a significant number of sera submitted for routine autoantibody screening which contain autoantibodies that are masked by the presence of heterophile antibody. Selective use of the absorption technique offers a simple solution to this problem.

Sera from 2,829 participants in a population health survey were tested for the presence of a heterophile antibody, detectable by immunofluorescence. The antibody was found in 9.8% of the sera from women and in 12.4% of the sera from men. The age-specific prevalence of the antibody was relatively constant in women but rose steeply in men. The antibody occurred more frequently in individuals with a history of blood transfusion and in multiparous females. It is suggested that the antibody may result from immunization by a ubiquitous agent which can be transmitted by blood transfusion.

[Editor's note: "Chance," wrote Louis Pasteur, "favors the prepared mind." Medical history abundantly illustrates the wisdom of this maxim. The paper by Paul and Bunnell offers one of the many examples of the maxim at work. Now that the Epstein-Barr virus has been identified and direct studies of infections due to this virus are possible, it is no longer necessary to resort to the heterophile test. Nevertheless, the test is still useful and, in the history of discovery of the Epstein-Barr virus, was invaluable.]

The earliest reports of illnesses resembling acute infectious mononucleosis (IM) appeared in the last two decades of the nineteenth century, but it was not until 1920 that the syndrome as we currently know it was described. The apparent lack of prior recognition of IM rests not on oversight but rather on the infrequency of this disease.

It is more than two decades now, since Paul and Bunnell described the heterophile antibody reaction as a diagnostic test for infectious mononucleosis and the disease became a well-established entity. But, after an analysis of the great variety of clinical cases, it became necessary to enlarge on the old concept that infectious mononucleosis presents itself solely as the glandular, anginose, or febrile type. Nevertheless, the diagnosis continues to be based upon the well-known triad of glandular enlargement, lymphocytosis, and a positive heterophile antibody reaction; although the adenopathy may confine itself to a limited area, the blood picture may not be very outspoken, and the serology may be negative in the early phase of the sickness. Since dermatologists and syphilologists have little opportunity to observe cases of infectious mononucleosis, dermatological literature is one of the few fields where contributions to the subject have been rather sparse. It is not

Until recently, the exclusive use of serum in all laboratory tests for detecting heterophile antibody has remained unquestioned. This communication describes a series of studies which demonstrate that comparable results are obtained when sequestrenized plasma is used instead of serum in the conventional differential absorption technique and in two slide screening tests. It is confirmed that significant differences in the final differential absorption titres can result from variations in the agglutinability of erythrocytes from different sheep but such differences when present are the same for plasma as for serum. The advantages of using plasma for routine purposes are briefly discussed.

A case of a false-positive test for the β-subunit of human chorionic gonadotropin as performed by the immunoradiometric assay is described. Further studies revealed that this problem was secondary to a cross-reacting heterophile antibody.

A patient who had documented mononucleosis in June 1971 has been persistently symptomatic since that time, with easy fatigability and weight loss. He has also had a positive differential heterophile antibody test for mononucleosis for 14 months. Although no evidence for active Epstein-Barr virus (EBV) infection was discovered, the possibility of a chronic EBV infection is discussed. (JAMA236:1492-1493, 1976)

Excerpt The sheep cell agglutination test or heterophile antibody reaction, as it is also called, is a laboratory procedure of considerable value in clinical medicine. In this country one frequentl...

The investigations of Bailey and Shorb 1 and of Jamieson, Powell, Bailey and Hyde 2 have prompted the addition of heterophile antibody, produced in rabbits, to the usual antipneumococcus serum in the treatment of human cases of pneumococcic lobar pneumonia. The justification for the use of such a mixture and the alleged claims for the superiority of such a product may be summarized briefly: 1. In human cases of pneumonia, just as in rabbits injected with cultures, the pneumococcus is said to exhibit the properties of a heterophile antigen. 2. The patient's pneumococci and the injected horse serum (which is known to be an active heterophile antigen) are said to combine with the natural heterophile antibody and render the latter inactive with regard to its alleged protective action against invasion by the pneumococcus. 3. This antigen-antibody combination may account for the "primary toxicity" of therapeutic horse serum and the untoward

Excerpt A human serum was found to contain a high titer of heterophile antibodies even though the patient suffered neither from serum sickness nor from infectious mononucleosis (so-called false Pau...

TO DATE, the heterophile antibody or Paul-Bunnell test has been considered one of the few specific laboratory tests, most investigators stating that only infectious mononucleosis, serum sickness or injections of liver can cause a diagnostic agglutination titer of 1:32 or higher by the Paul-Bunnell method or of 1: 56 or higher by the more commonly used Davidsohn modified technic.1 In the laboratory of Research Hospital, my colleagues and I have in the past twenty-three months made a total of five hundred and three tests on 220 different patients, using exclusively the Davidsohn technic, with readings taken after overnight incubation in the refrigerator. Since many of these tests have been done on outpatients whose complete records were not accessible, the study is limited to 141 patients, representing only those for whom diagnosis was made after examination of tissue either on their admission to Research Hospital or on their examination at the