An Antigen Detected Frequently in Human Sera With Elevated Levels of Alanine Aminotransferase: A Potential Marker For Non-A, Non-B Hepatitis

Neurath, A. R.; Stevens, Cladd E.; Strick, N.; Szmuness, Wolf; Oleszko, W. R.; Harley, Edward J.

doi:10.1099/0022-1317-48-2-285

Cited by 14 publications

(16 citation statements)

References 12 publications

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“…Clinical diagnosis and identification of NANB hepatitis has been accomplished by enzyme serology and exclusion of other viral markers. A number of laboratories have attempted to identify specific NANB hepatitis virus antigen-antibody reactions by a variety of methods (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). To date, neither specific antigen nor antibody has been identified.…”

mentioning

confidence: 99%

Detection of non-A, non-B hepatitis antigen by immunocytochemical staining.

Burk¹,

Oefinger²,

Dreesman³

1984

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

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Liver tissue obtained from a chimpanzee during the acute phase of an experimental non-A, non-B (NANB) hepatitis virus infection was studied by a sensitive immunocytochemical staining procedure for the presence of NANB viral antigens. Initial investigations were conducted with a model system of hepatitis B virus (HBV) antigens for purposes of comparing two immunocytochemical staining methods. Of these two procedures, an immunoperoxidase procedure, utilizing an avidin-biotinylated enzyme complex, was at least 40-fold more sensitive than a conventional immunoperoxidase technique for the detection of HBV-specific tissue antigens. Utilization of the avidin-biotin-amplified immunoperoxidase staining procedure, in conjunction with four primary convalescent antisera obtained from NANB hepatitis-implicated donors, resulted in the observation of NANB virus-associated antigen in the cytoplasm of hepatocytes from an infected chimpanzee liver. These same human antisera were not reactive with a number of uninfected control cells nor with cells infected with HBV, hepatitis A virus, or cytomegalovirus. Preincubation of one of these convalescent NANB sera, or IgG derived thereof, with an acute-phase serum obtained from a NANB hepatitis virus-infected chimpanzee abolished the antibody reactivity. We conclude from these observations that selected convalescent sera from NANB hepatitis virus-infected patients contain low levels of antibody that specifically react with a cytoplasmic antigen associated with NANB virus-infected hepatocytes.Non-A, non-B (NANB) hepatitis has been recognized as a virus-induced disease that is distinct from other forms of viral-associated liver diseases, including hepatitis A virus (HAV) and hepatitis B virus (HBV), and the hepatitides induced by cytomegalovirus or Epstein-Barr virus (1-3). Clinical (19,20). In addition, studies in chimpanzees involving the chronic sequelae associated with NANB hepatitis now appear to be more serious than chronic disease developments arising from HBV infection (21-23).In an effort to study the various aspects of this serious human disease, chimpanzees have been shown to be suitable experimental models that are susceptible to NANB hepatitis virus infection (2,3,16,17,24). The reagent materials (NANB antigen) obtained from experimental animals have been used in conjunction with presumed convalescent human antibody to NANB in attempts to demonstrate immunological reactions with specificity for NANB hepatitis antigen. The present study describes a highly sensitive immunocytochemical procedure that utilizes NANB-infected chimpanzee liver expressing NANB antigen and human convalescent sera containing anti-NANB.Control and specificity studies are described herein that provide convincing evidence for the specificity of the NANB hepatitis virus immunocytochemical reactivity. MATERIALS AND METHODSChimpanzee Materials. Liver biopsy material was obtained from four chimpanzees (nos. 90, 92, 94, and 159) infected with human plasma containing infectious NANB hepatitis virus (1...

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mentioning

confidence: 99%

Detection of non-A, non-B hepatitis antigen by immunocytochemical staining.

Burk¹,

Oefinger²,

Dreesman³

1984

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

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“…Undiluted specimens or samples serially diluted in 0.14 M NaCl-0.01 M Tris-0.02% NaN3, pH 7.2 (TS), containing 2.5 mg/ml of bovine serum albumin (TS-BSA) were tested for CDA1 by solid-phase RIA as described before [7,8]. The source of anti-CD Al used for coating of polystyrene beads and for labeling was hemophiliac serum MS.…”

Section: Radioimmunoassay (Ria)mentioning

confidence: 99%

“…IgG isolated from serum MS by chromatography on DEAE-cellulose [7] was linked to CNBr-activated Se pharose 6 MB following the instructions of the manu facturer (Pharmacia, Piscataway, N.J.). 1ml of a 15% erythrocyte suspension in TS was applied to a 1.8-ml column of anti-CDAl linked to Sepharose.…”

Section: Affinity Chromatography Of Erythrocytesmentioning

confidence: 99%

“…The frequency of the antigen varies in different races. Studies in Caucasian families revealed an autosomal-dominant inheritance of the antigen.temporarily as cytoplasmic-dominant anti gen 1 (CDA1) instead of the originally pro posed term of hepatitis-related antigen An apparently new antigen was detected recently [7] with high frequency in human sera with elevated levels of alanine amino transferase (ALT). The antigen appeared transiently at the time of elevated ALT in sera of many individuals who were infected with either hepatitis A, B or non-A, non-B viruses.…”

mentioning

confidence: 99%

“…The search led to the discovery of an intra cellular alloantigen described in this report. Since the exact nature of the antigen has not yet been determined, it will be designated (HRA) [7], …”

mentioning

confidence: 99%

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Discovery of a Cytoplasmic-Dominant Alloantigen Prevalent in Erythrocytes

Neurath¹,

Strick²,

Rowe³

et al. 1981

Vox Sanguinis

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Rheumatoid factor-like reactants in sera proven to transmit non-A, non-B hepatitis: A potential source of false-positive reactions in non-A, non-B assays

Shiraishi¹,

Alter²,

Purcell³

1985

Hepatology

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Convalescent phase non-A, non-B (NANB) human and chimpanzee sera were utilized in a solid-phase radioimmunoassay (RIA) in an attempt to identify a specific NANB antigen in human plasma, plasma-derived pellets and NP-40 disrupted pellets proven to transmit NANB infection to chimpanzees. RIA reactivity was noted in 5 of 8 pedigreed NANB infectious plasmas, but did not appear to be virus-specific. The RIA reactive fraction: (i) had a density of 1.27 to 1.32 gm per cm3 in cesium chloride; (ii) showed immunoreactivity corresponding to normal IgM, but peak RIA activity coincided with an aberrant IgM having a peak sedimentation coefficient of 56 S, and (iii) eluted at higher pH (5.6 to 5.0) than normal IgM on chromatofocusing columns. The reactant shared properties with rheumatoid factor in that it was absorbed by aggregated IgG and was unstable to 2-mercaptoethanol, but it did not react in standard agglutination tests for rheumatoid factor. The reactant was detected in both the acute and chronic phase of NANB infections in chimpanzee and man. By reacting with IgG in presumptive NANB convalescent sera, this aberrant rheumatoid factor could simulate a NANB antigen and represent a cause of false-positive reactions in putative NANB assays.

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An Antigen Detected Frequently in Human Sera With Elevated Levels of Alanine Aminotransferase: A Potential Marker For Non-A, Non-B Hepatitis

Cited by 14 publications

References 12 publications

Detection of non-A, non-B hepatitis antigen by immunocytochemical staining.

Detection of non-A, non-B hepatitis antigen by immunocytochemical staining.

Discovery of a Cytoplasmic-Dominant Alloantigen Prevalent in Erythrocytes

Rheumatoid factor-like reactants in sera proven to transmit non-A, non-B hepatitis: A potential source of false-positive reactions in non-A, non-B assays

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