To determine the frequency of vertical transmission of hepatitis B antigen (HB5 Ag) from asymptomatic carrier mothers in Taiwan to their offspring, HB5 Ag was sought by radioimmunoassay and complement fixation. Of 158 babies born to carrier mothers, antigenemia developed in 63; 51 of these antigenemic babies had become antigen positive within the six months of life. Three inter-related factors were found to increase the risk that antigenemia would develop in the infant: a high maternal complement-fixation titer for HB5 Ag: presence of HB5 Ag in the baby's umbilical-cord blood: and antigenemia in siblings. In contrast to previous studies, these findings indicate that vertical transmission from carrier mothers frequently occurs, at least in Taiwan, and may partially explain Taiwan's high prevalence of HB5 Ag.

https://www.nejm.org/doi/pdf/10.1056/NEJM197504102921503?listPDF=true

Vertical transmission of hepatitis B antigen in Taiwan.

A sensitivie and simple procedure for the detection and quantitation of soluble complement (C)- fixing immune complexes in sera of patients with various disease states has been developed by utilizing C receptors on Raji cells. These cells lack membrane-bound immunoglobulin but have receptors for IgG Fc, C3b, C3d, and possibly with other C proteins. Uptake experiments showed that both aggregated human gamma globulin (AHG) and 7S IgG bound to receptors for IgG Fc; however, AHG reacted with C bound to cells only via receptors for C and this binding was much more efficient than via IgG Fc receptors. AHG was used as an in vitro model of human immune complexes and its uptake by Raji cells was quantitated by 125I-radiolabeled antihuman IgG. The limit of sensitivity of this test was 6 mug AHG/ml serum. The ability of Raji cells to detect AHG in serum depended on the amount of radioactive antibody used and the size of aggregates. The presence of an excess of C somewhat inhibited binding of AHG containing C to Raji cells. The efficient binding of AHG by receptors for C on Raji cells was used for the detection and quantitation of immune complexes in human sera. Raji cells were incubated with sera to be tested and then reacted with excess radiolabeled antihuman IgG; the amount of radioactivity bound to the washed cells was determined and referred to a standard curve of radioactive antibody uptake by cells previously incubated with increasing amounts of AHG in serum. Thereby immune complexes were detected and quantitated in serum hepatitis, systemic lupus erythematosus, vasculitis, subacute sclerosing panencephalitis, dengue hemorrhagic fever, and malignancies.

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The Raji cell radioimmune assay for detecting immune complexes in human sera.

Publisher Summary No experimental model has provided greater insight into the mechanism of immune complex disease than the experimental serum sickness. The morphological, immunohistological, and serological features of the laboratory models have provided a basis for understanding the pathogenic mechanisms responsible for human glomerulonephritis, vasculitis, and a variety of systemic connective tissue diseases. The subject of experimental acute and chronic immune complex disease produced by nonliving antigens has received extensive review in this series. This chapter summarizes the data presented in these two reviews and discusses in detail more recent studies. Experiments to study acute immune complex disease (serum sickness) have been performed in rabbits almost exclusively. Experimental chronic immune complex disease has proved to be a most useful model in understanding human glomerulonephritis. When injected daily with heterologous serum protein antigens, rabbits with strong antibody responses develop chronic membranous glomerulonephritis in about 5 weeks.

Immune Complex Disease in Experimental Animals and Man

Four patients with chronic hepatitis B infection and chronic active hepatitis were treated with human leukocyte interferon. Three of them had consistently elevated levels of circulating Dane-particle markers, including Dane-particle-associated DNA polymerase activity, hepatitis B core antigen and Dane-particle-associated DNA. Parenteral interferon administration at a dosage between 6.0 X 10(3) and 17 X 10(4) U per kilogram per day was associated with a rapid and reproducible fall in all Dane-particle markers in the three patients. The suppressive effect was transient when the interferon was given for 10 days or less but appeared to be more permanent when administration was prolonged for a month or more. In addition, long-term interferon therapy was associated with a marked fall in hepatitis B surface antigen in two of three patients and a disappearance of e antigen in two of two patients. Interferon may be useful in limiting carrier infectivity or eradicating chronic infection.

https://www.nejm.org/doi/pdf/10.1056/NEJM197609022951001?listPDF=true

Effect of Human Leukocyte Interferon on Hepatitis B Virus Infection in Patients with Chronic Active Hepatitis

Hemagglutination assays are described for measuring hepatitis-associated Australia antigen and antibody. Red cells coated with isolated antigen, with chromic chloride as a coupling agent, are used for detection of antibodies. Detection of the antigen in serums depends on inhibition of hemagglutination. The test has the sensitivity and rapidity of the best tests available, is simpler to perform, and lends itself to large-scale screening of blood donors.

https://science.sciencemag.org/content/sci/170/3955/332.full.pdf

Hemagglutination Assay for Antigen and Antibody Associated with Viral Hepatitis

Complement fixation techniques are described for measuring a virus-like antigen associated with viral hepatitis Antigen was found in the blood of 98 percent of 130 patients, with the serum form of hepatitis, from whom multiple samples were obtained Antibodies arising during hepatitis are usually combined with antigen and cause anticomplementary activity in the serum, which is reversible with excess antigen or antibody Tests for antigen and specific anticomplementary activity can be used diagnostically and to screen blood donors for hepatitis carriers

https://science.sciencemag.org/content/sci/165/3890/304.full.pdf

N. Raphael Shulman

Papers

Virus-like antigen, antibody, and antigen-antibody complexes in hepatitis measured by complement fixation.