Population studies showing cross-reactivity of Toxoplasma gondii antibodies with antibodies to malignant cervical tissue antigens.

Antibody inhibition studies have established that ethanol-soluble extracts prepared from a pool of malignant cervical tissues contained substances capable of reacting with antibodies specific for Toxoplasma gondii and malignant tissue factors. Extracts from normal cervical tissue did not possess Toxoplasma or malignant tissue antigens. Antibodies to malignant cervical tissue extract could be detected singly or in combination with Toxoplasma antibodies. The overall incidence of antibodies to malignant tissue extract in over 2,000 samples of blood tested was 4.4%. Of 98 apparently healthy donors with antibodies to malignant tissue extract, 50% also possessed Toxoplasma antibodies. The combined incidence of anti-Toxoplasma activity was 16.5% of all samples tested. Methods for the isolation and determination of IgG antibodies to malignant tissue and Toxoplasma antigen extracts are described, and the possible significance of the findings discussed.

A study of ABO incompatibility and neonatal jaundice in Black South African newborn infants.

In order to establish the role of fetomaternal ABO incompatibility as a cause of overall neonatal jaundice, its relationship to the degree of jaundice, and its etiologic contribution to severe jaundice necessitating exchange transfusion in South African blacks, a retrospective analysis of both laboratory and clinical data was undertaken. Two thousand forty-two blood samples were submitted for laboratory investigation from mothers and their jaundiced newborn infants and categorized according to ABO blood groups and levels of serum bilirubin. At levels of serum bilirubin below 301 mumol/l, ABO incompatible combinations occurred as frequently as ABO compatible combinations. However, at serum bilirubins above 301 mumol/l, ABO incompatibility was a major cause of jaundice in almost 58 per cent of infants. In the nursery-based clinical studies, ABO incompatibility accounted for 41.7 per cent of those severely jaundiced (greater than 301 mumol/l) and 44.4 per cent of newborn infants who had exchange transfusions. ABO incompatible combinations however did not assume a significant role in the cause of overall neonatal jaundice. Both laboratory and clinical findings therefore confirm the importance of fetomaternal ABO incompatibility as a cause of severe jaundice and an unimportant cause of overall jaundice in newborn black babies.

The effect of seromucoid on coagulation.

The purpose of this study was to investigate the effect on coagulation of alpha-acid-glycoprotein, one of the acute-phase reactants, the blood level of which is elevated in malignant disease and various acute conditions. Alpha-acid-glycoprotein was obtained from serum and plasma of normal volunteers. The amount obtainable from serum was greater than that obtained from plasma (43 mg/dl v. 22 mg/dl), and differences were noted in the molecular weight of the two preparations; alpha-acid-glycoprotein from serum had a molecular weight of 55 000, while that from plasma appeared to have a molecular weight of 81 000. The two preparations were identical in their reactivity towards anti-alpha-acid-glycoprotein. Alpha-acid-glycoprotein markedly shortened the partial thromboplastin time (PTT), but no effect on prothrombin index was noted. At those concentration which shortened the PTT, the preparation was able partially to reverse the anticoagulant activity of heparin. The possibility that this protein plays a role in the aetiology of coagulation disorders in cancer is discussed.

Heterophile antibodies, immunoglobulin levels, and the evaluation on anti-T activity in cancer patients and controls.

In a study of human agglutinin response to multideterminant ABH-like antigens, such as sheep red blood cells (SRBC), a significant correlation was found between the presence of high antibody levels to such red cells (titres of 1:20 and higher) and total serum concentrations of IgM and IgA.. Individuals with lower levels of SRBC agglutinins (titres of 1:10 and lower) generally have reduced concentrations of these two classes of immunoglobulin. High or low levels of antibody to SRBC did not correlate with the development of several kinds of malignant tumour (cervix uteri, breast and oesophagus). It was found, however, that procedures of high levels of agglutinins for SRBC, whether cancer patients or normal subjects, also more often produce higher levels of antibodies to the cryptantigenic T (Thomsen-Friedenreich)-antigen structure of human red cells. The only significant difference is that cancer patients have persistently depressed levels of anti-T. This provides further evidence that malignant tissue may have exposed T-Antigen structures on their membranes.

Antibody responses to T-activated red cells in children from high- and low-risk areas of cancer of the oesophagus in Transkei.

Information is presented on the role of humoral anti-T activity in children residing in areas of Transkei where the incidence of cancer of the oesophagus ranks among the highest in the world. It is significant that children from high-risk areas produce elevated levels of antibodies to the cryptantigenic T structure of autologous cell membranes more often than those from low-risk areas (X2(1) = 32; P less than 0,0005). The extreme variations recorded in anti-T response between these two groups of children could not be related to a greater prevalence of viral infections or other susceptible childhood diseases. Available evidence suggests that the observed differences in anti-T activity may be closely related to environmental nutritive imbalances, some of which are known to be significantly correlated with the high-incidence foci of cancer of the oesophagus in Transkei.

Hepatitis B antigen and antibodies in rural and urban Southern African blacks.

Random samples which represented Blacks living in an urban area (Durban) and a rural area (Transkei) of the east coast of southern Africa were investigated for the incidence and distribution of hepatitis B antigen and antibodies. The overall prevalence of carriers of the virus was higher in rural communities (15,5%) than in the urban population (7,4%). In adults the formation of antibodies to the virus correlated with the pattern of increased activity of the hepatitis B carrier. Similar correlations could not be made for children living in the rural area. Of significance was the observation that the high carrier rate of the virus (17%) was more often associated with a reduced development of antibodies to the virus. Evidence for a depressed immunity and inability to make hepatitis B antibodies in these children is thought to be linked with the high prevalence of other forms of endemic infections, particularly acute measles.

Hepatic infections. Part II. The effect of acute and chronic hepatitis B antigenaemia on the reaction to antibodies to sheep red cells (microbial antigens) and human T-activated cells (exposed autologous tissue antigens).

Using the agglutination of sheep red cells by human antibodies as an indicator of microbial antibody activity, a highly significant association was found between the response to the e antigen of the hepatitis B virus and the formation of strong antibody levels to microbial substances (chi 2(1) = 33). This kind of association was not found among chronic carriers of the hepatitis B virus who do not produce antibodies to the e antigen (chi 2(1) = 3,7). In the presence of e antigen activity, patients with acute virus B hepatitis almost always show significantly reduced levels of antibodies to microbial substances (chi 2(1) = 20). The findings indirectly reveal that e activity is associated with the inability of the liver to trap bacterial antigens. Circumstantial evidence further suggests that the e factor may bear antigens on its immunoglobulin-like structure very similar to microbial cell wall components. Accepting that human antibodies to the T (Thomsen-Friedenreich) antigen represent reactions to cryptantigenic membrane structure of autologous tissues, it was significant to record that increased anti-t activity is always demonstrated when virus B infections progress from the acute to the chronic carrier stage (chi 2(1) = 73). The most intense anti-T activity is commonly found in subjects who produce antibodies to the hepatitis B surface antigen (chi 2(1) = 138). In the presence of e antigen the amount of anti-T in circulation is always significantly depressed. Since this type of depression is not seen in patients with acute virus B hepatitis who lack the e antigen, we suspect that the reduced anti-T levels in e antigen-positive patients are linked with the in vivo exposure of T receptors by microbial neuraminidase.

Hepatic infections. Part I. A serological evaluation of Fab antigens (Fab' and F (ab)2) and antibodies in patients and asymptomatic carriers of hepatitis B virus.

Evidence for the association of Fab (antigen-binding) fragments of IgG and antibodies directed against receptors of these fragments (Fab' and F(ab)2) has been found in patients and asymptomatic carriers of hepatitis B antigen. Fab fragments of IgG are often detected in hepatitis B surface antigen (HBsAg)-positive sera where the intensity of antibody activity to these determinants is significantly reduced. The formation of strong antibodies to Fab fragments is often observed in association with the presence of hepatitis B surface antibodies (HBsAb). Comparative studies show that the appearance of Fab fragments in HBsAg-positive sera is not linked to the presence of hepatitis e antigen. This observation was supported by the finding of autologous Fab fragments of IgG in e antibody-positive sera. It was also established that the amount of Fab fragment in the serum is closely associated with the detection of high HBsAg titres. Preliminary investigations suggest that the Fab fragments of IgG detected in the serum of HBsAg-positive patients represent in vivo-digested HBsAb attached to the surface membrane of virus B particles. Further studies are in progress to determine the relationship of Fab fragments with a variety of other immunological events, especially the role of liver enzymes in the cleavage of intact antibodies.

Heterophile antibodies. Part II. An evaluation of the effect of autologous blood group substances on the natural formation of agglutinating antibodies to sheep red blood cells.

This study shows that some substances in human secretions can inhibit the agglutination of sheep red blood cells by human antibodies. When present in adequate concentrations, they can also inhibit the reaction of the donor's own sheep red blood cell antibody activity in vito. The subjects in whom this phenomenon was found almost always had low agglutinating antibody titers to sheep red blood cells. The inhibiting activity of saliva for sheep red blood cell antibodies was influenced by the ABH secretor status. Substances reacting against sheep red blood cell antibodies occur in the secretions in considerably smaller quantities than ABH substances.

Heterophile antibodies. Part III. Evidence for linkage of high responder activity to sheep red blood cells and the formation of specific antibodies to HBsAg.

Group A, B and O subjects who produce immune antibodies to group A1 or B red blood cells also produce high titer antibodies to sheep red blood cells. Sheep red blood cells appear to possess AB-like as well as non-AB determinants on their surface membranes, each capable of producing and reacting with antibodies of their respective specificities. The antibodies against AB-like determinants preferentially agglutinate A or B cells whereas non-AB-like determinants preferentially stimulate hemolytic antibodies. Human antibodies reacting with these two kinds of determinants on sheep red blood cells may be produced in response to microorganisms possessing very similar factors on their membranes. Individuals who possess AB-like determinants in their secretions, similar to the determinants present on sheep red blood cells (or microorganisms), often make weaker antibodies to these red blood cells. Subjects lacking corresponding anti-sheep inhibitors in their secretions generally produce stronger sheep red blood cell antibodies. There is a positive correlation between the formation of antibodies to HBsAg and strong agglutinating antibodies to sheep red blood cells, indicating that similar determinants may be found on HBsAg virus and on sheep red blood cells. No such correlation was found for anti-tetanus antibodies.

Serological studies of seromucoids from normal subjects and patients with malignant and non-malignant diseases.

During investigations of serum from patients with carcinoma, elevated levels of two proteins were observed. The larger (MW approximately 44,000) was identified as (alpha-acid glycoprotein. The smaller MW approximately 20,000) has not yet been identified. Further investigation of alpha-acid-glycoprotein-containing seromucoid showed that many red blood cell and tissue antigens were present, for example, I, i, P1, Tja (P+P+Pk), H, A, B, Lea, Leb1, M and N. Differences in antigen content between normal serum and serum from carcinoma patients could be demonstrated quantitatively and qualitatively. Seromucoid preparations from patients with Hodgkin's lymphoma inhibited phytohaemagglutinin-induced lymphocyte transformation more often than seromucoid preparations from normal subjects.

Alterations in immune responsiveness in acute measles and chronic post-measles chest disease.

Immune responses in 24 children with acute measles (AM) were compared with those in 20 children who had chronic pulmonary complications (CPMC) following measles. The immuno-suppressive effects of acute measles were extensive: total white cells were reduced and this reduction was accounted for entirely by lymphopenia which was equally expressed among the major lymphocyte sub-populations studied; the function of 'T' cells, assessed by radio-isotope incorporation into phytohaemagglutin (PHA) transformed lymphocytes and delayed skin hypersensitivity (DHR) to dinitrochlorobenzene (DNCB), was depressed. Serum IgA was reduced in AM patients. In contrast there was a relative sparing of the measured indices of immunity in patients with chronic post-measles chest disease, with the major defect being an impaired DHR to DNCB. There were minor alterations of complement components in both groups of patients.

Anti-fab' antibodies in human sera. II. A study of their possible association with C-reactive protein, rheumatoid and anticomplementary factors.

The present study was undertaken to determine whether a relationship could be found between Fab' antibodies and the occurrence of C-reactive protein, rheumatoid and anticomplementary factors in the serum of patients with malignancies and other illnesses. The findings argue against the possibility that Fab' antibody activity is associated with a single disease entity. The very frequent occurrence of Fab' antibodies in hospital patients as opposed to healthy blood donors implies that their function is probably indirectly related to other immunological events. There is evidence to suggest that Fab' antibodies may serve as a mechanism for clearing immune complexes.

Anti-fab' antibodies in human sera. I. A study of their distribution in health and disease.

Antibodies to the Fab' fragments of human IgG are commonly found in human sera. This study shows that the incidence of such antibodies is higher in women, both blood donors and hospital patients, than in men: it is no higher in patients with malignant disease than in hospital patients of the same sex without malignancies. The incidence in hospital patients is always greater than in healthy blood donors. The presence of Fab' antibodies is not related to pregnancy. The greatest difference in the frequency of such antibodies occurs between males and females under the age of 50.

Immunoparesis and outcome in measles.

In five children with measles who subsequently died and in one with measles in whom chronic bronchopneumonia developed (group A), immunosuppression was more pronounced during the acute rash (i.e., 3-20 days before death) than in six children with measles who recovered (group B). The absolute total lymphocyte-count (T and B cells) was significantly lower in group A. Mean serum-C3 was also lower in group A than in group B. There were no significant differences between the two groups for other complement factors or for serum-immunoglobulins. The mean phytohaemagglutinin stimulation index (S.I.) for lymphocytes from patients in group A resembled that in group B, although the S.I. in both groups was significantly lower than that in healthy controls. S.I.S were lowest in two patients who died. Counts of total white cells, neutrophils, null cells, and those with both B and T cell markers were not significantly different in groups A and B. The total lymphocyte-count (mean 2117 +/- S.E.M. 375 cells/mm3) in a further nineteen patients with measles who had died, studied retrospectively, was significantly lower than that (4487 +/- 540 cells/mm3) in twenty-seven patients with measles who recovered.

Hemagglutination inhibition studies of water soluble blood group substances recovered from the erythrocytes of classical Bombay Oh subjects.

Using ethanol and acetone fractionation to isolate soluble blood group substances from red blood cells, 'Bombay' Oh bloods were found to contain variable amounts of concealed H substance. The IgG variety of anti-H in 'Bombay' bloods has a greater affinity for these substances than the IgM variety of anti-H. Group O parents of 'Bombay' Oh subjects were found to have normal levels of H substance, indicating that individuals heterozygous for a recessive suppressor gene 'x' synthesize it normally. In the 'Bombay' family studied, Lewis determinants were abnormally expressed in two members. Lewis activity was detected in the soluble extracts of their red blood cells but not by the direct agglutination test. Further tests using known Le(a-b-) types are necessary to determine whether these findings are linked to the 'Bombay' Oh phenomenon.

Hemagglutination inhibition studies for the evaluation of blood group antigens in ethanol soluble substances (ESS) obtained from human, baboon and vervet monkey red blood cells.

Soluble blood group substances, isolated from the red blood cells of humans, baboons, and vervet monkeys by ethanol extraction, possessed serologically active specificities for the following antigens: A, B, H, Lea, LebL, P, P19 Pk and I. Human red blood cells lacking any of these specificities by the direct hemagglutination test also lacked the related antigens in their soluble extract. The only exception was in "Bombay" Oh cells, from which soluble H substance could be readily isolated. Soluble substances obtained from baboon and vervet monkey red blood cells, which lack the human variety of A, B, and H antigens on their red blood cells, inhibited both human and lectin anti-H reagents. The detection of "hidden" H activity in Oh cells will pose some important questions regarding membrane characteristics and the role of immune surveilance.

A family with partial and total deficiency of complement C3.

A young White girl was found to have no detectable complement C3 or C1q. She suffered repeated attacks of pneumococcal meningitis and pneumococcal pneumonia. Her parents, and some of her siblings, had half the normal level of C3; other siblings were normal. She also had decreased IgG levels and increased IgM concentrations. These findings are correlated with a dysmorphic state of the germinal centres of the peripheral lymphoid tissues, seen after death.