Australia antigen as a hepatitis virus

Blumberg, Baruch S.; Sutnick, Alton I.; London, W. Thomas

doi:10.1016/0002-9343(70)90093-8

Cited by 218 publications

(42 citation statements)

References 22 publications

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“…The pathological manifestations of HBV infections are determined by differences in the host's immunologic response (28,29). The association of eAg with active replication of HBV in HB5Ag-positive liver disease and of eAb with the HBSAg carrier state without apparent liver disease (7,(9)(10)(11), except primary hepatic carcinoma (30), suggests that eAg plays a crucial role in determining the outcome of HBV infections.…”

Section: Discussionmentioning

confidence: 99%

Host specificity of a serum marker for hepatitis B: evidence that "e antigen" has the properties of an immunoglobulin.

Neurath¹,

Strick²

1977

Proc. Natl. Acad. Sci. U.S.A.

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A family of antigens, referred to collectively as e antigen (eAg), has been detected in sera of some individuals with liver disease who test positive for hepatitis B surface antigen. Studies on eAg partially purified by affinity chromatography on insolubilized antiboies to eAg revealed the following: (i) (eAg). Though distinct from HBsAg in both immunologic and physicochemical properties (8), eAg is also specifically associated with HBV infections and appears to be a marker for the infectivity of HBsAg-positive sera (7, 9, 10); its persistence seems to be associated with chronic liver disease (11). Our attempts to characterize eAg, described here, led to the surprising finding that eAg has the properties of an immunoglobulin. MATERIALS AND METHODSeAg was partially purified by precipitation with polyethylene glycol 6000, followed either by affinity chromatography on columns of insolubilized antibodies to eAg (eAbl (12) or by chromatography on DEAE-Bio-Gel (13). eAb was prepared from human sera by sequential precipitation with Rivanol and Na2SO4 (14). Antibodies to individual human plasma proteins and to IgG subclasses were each linked to Sepharose 4B as described (15). Normal human serum or IgG was insolubilized by the same procedure.Partially purified eAg (total amount of protein: 90-250 mg in 30 mM sodium citrate, pH 7.4) was submitted to isoelectric focusing (16). Fractions after isoelectric focusing were adjusted to pH 7, dialyzed against 0.14 M NaCl/0.01 M Tris-HCI at pH 7.2 (Tris/saline), concentrated about 10-fold, and tested for eAg. Identical results were obtained with either the cathode or the anode positioned in the bottom of the electrofocusing column.To compare the sedimentation rates of eAg and an IgG (18), respectively. The F(ab')2 fragments were isolated by chromatography on Sephadex G-150 (17). The Fab fragments were separated from Fc fragments by affinity chromatography on anti-Fab columns. F(ab")2 fragments from samples containing eAg were prepared by cleavage with CNBr (19), followed by affinity chromatography on anti-Fab columns.eAg purified by affinity chromatography or proteins eluted with 50 mM Na2B407 (pH 10.9) from extensively washed eAg-eAb precipitin lines excised from the agarose gel of rheophoresis plates were each labeled with 1251 (20) or with [125I]-iodinated p-hydroxyphenylpropionic acid N-hydroxysuccinimide ester (Bolton-Hunter reagent; New England Nuclear, Boston, MA). Similar results were obtained by either of the two methods. Labeled eAg was further purified by isoelectric focusing. Fractions collected in the pH range of 4.9-5.7 were pooled, dialyzed against Tris/saline, mixed with 2 ml of lamb serum and with normal human serum proteins, precipitated from 10 ml of serum with polyethylene glycol 6000 (600 mg), and resuspended in 2 ml of Tris/saline. Labeled eAg from this mixture was repurified by affinity chromatography on a 15-ml column of insolubilized eAb.The method for polyacrylamide gel electrophoresis described earlier (16) was used. Samples were dissociated...

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Section: Discussionmentioning

confidence: 99%

Host specificity of a serum marker for hepatitis B: evidence that "e antigen" has the properties of an immunoglobulin.

Neurath¹,

Strick²

1977

Proc. Natl. Acad. Sci. U.S.A.

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“…Host cellular and humoral immune responses are suspected of being important. Thus the chronic carrier state is particularly common among individuals with conditions or diseases associated with significant immunologic hyporesponsiveness, such as newborns, patients receiving immunosuppressive agents or undergoing renal dialysis and patients with Down's syndrome, Hodgkin's disease, acute leukemia, and lepromatous leprosy (2)(3)(4). However, the great majority of chronic HBsAg carriers are otherwise normal individuals, in whom no appreciable generalized immunologic deficiency can be demonstrated (5).…”

mentioning

confidence: 99%

Synthesis of antibodies to hepatitis B virus by cultured lymphocytes from chronic hepatitis B surface antigen carriers.

Dusheiko¹,

Hoofnagle²,

Cooksley³

et al. 1983

J. Clin. Invest.

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A B S T R A C T It hasIn order to identify the mechanisms for the lack of detectable anti-HBs synthesis by chronic HBsAg carrier lymphocytes, co-culture experiments were performed using T and B lymphocyte fractions that had been purified by affinity chromatography. B lymphocytes from carriers co-cultured with allogeneic irradiated ("helper") T lymphocytes from controls synthesized normal amounts of IgG, IgM, and anti-HBc Dr. Dusheiko was the recipient of a South African Research Council Overseas Scholarship. His present address is

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“…Screening for Au(l) in the blood of apparently healthy donors in the blood bank of this medical institution has yielded a carrier rate of 1.2%. This slightly exceeds the carrier rate in the USA and that in Western Europe [2]. While this factor might influence the number of cases and perpetuation of dialysis unit out breaks it does not provide any qualitative or quantitative information to explain the nature of viral hepatitis encountered.…”

Section: Discussionmentioning

confidence: 85%

“…This variety of virus-associated hepatitis has previously been described in <i) institutionalised patients with Downs syndrome, (ii) lepromatous leprosy, (iii) leukaemia [2], and (iv) immunosuppressed allograft recipients [13.15,16],…”

Section: Discussionmentioning

confidence: 97%

‘Normal’ Host Response to Au (1) – Associated Hepatitis Virus Outbreak in a Chronic Dialysis Unit in Israel

Myers

Sharon

Rosenfeld

1972

Nephron

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During a 2-year observation period 8 out of 56 patients treated in a chronic dialysis unit in Israel developed viral hepatitis which has the features of serum hepatitis. Six of those affected (75%) had symptomatic acute illnesses, recovered in a short period and Australian antigen – Au(1) -could not be detected in their convalescent serum. In this pattern of response to the virus they differ markedly from dialysis patients reported in the USA and Western Europe and tend to resemble the pattern of illness encountered in the staff of these units. This would seem to cast doubt upon the generally expressed view that the uraemic state per se by altering host responsiveness is responsible for the persisting Au(1) antigenaemia and persistent hepatitis generally reported from dialysis units.

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Australia antigen as a hepatitis virus

Cited by 218 publications

References 22 publications

Host specificity of a serum marker for hepatitis B: evidence that "e antigen" has the properties of an immunoglobulin.

Host specificity of a serum marker for hepatitis B: evidence that "e antigen" has the properties of an immunoglobulin.

Synthesis of antibodies to hepatitis B virus by cultured lymphocytes from chronic hepatitis B surface antigen carriers.

‘Normal’ Host Response to Au (1) – Associated Hepatitis Virus Outbreak in a Chronic Dialysis Unit in Israel

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