Yuzo Miyakawa

DEFECTIVE IMMUNE-ADHERENCE (C3b) RECEPTOR ON ERYTHROCYTES FROM PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Erythrocytes from 56 patients with systemic lupus erythematosus (SLE) were tested for the immune-adherence (C3b) receptor reactivity for incubation with aggregated human gamma-globulin (AHG) in the presence of complement. The reactivity of the C3b receptors was expressed as the highest two-fold dilution of AHG that induced haemagglutination. Erythrocytes from 37 (66%) of the SLE patients failed to show any detectable reactivity with AHG, whereas the erythrocytes of only 1 of 51 normal controls matched for age and sex were found to be unreactive. The defect of the C3b receptor reactivity was persistent and could not be restored even after SLE patients had gone into remission with steroid therapy. Moreover, the defect was found frequently in the relatives of patients without detectable immune-adherence reactivity. Owing to its high prevalence and persistence in SLE, the defective erythrocyte C3b receptor may be a useful marker for identifying SLE patients and those predisposed to the disease.

Hepatitis B surface antigen in the serum of infants after delivery from asymptomatic carrier mothers

A survey of sera of 5,993 pregnant women for hepatitis B surface antigen in Tokyo revealed 139 asymptomatic carriers (2.3%), essentially the same as that of a control population of comparable age group (2.2%). None of 59 specimens of cord blood of their newborn infants was positive for HBsAg according to an immune adherence hemagglutination assay. In 11 mother-child pairs in whom follow-up was possible for more than seven months, HBsAg was detected in the sera of eight infants within the first six months, after birth, with antigenemia persisting throughout the observation period, while antigenemia was not detected in the remaining three. The subtype of HBsAg was identical for each mother-child pair. The antigen was detected in sera of two of the infants after appropriate incubation periods of 123 and 133 days, respectively, whereas in others it was detected as early as 5 and 13 days after delivery.

Posttransfusion Fulminant Hepatitis B Associated with Precore‐Defective HBV Mutants

Abstract. Fulminant hepatitis B developed in 8 recipients of blood units without detectable hepatitis B surface antigen on routine screening. All 124 hepatitis B virus (HBV) DNA clones propagated from their sera possessed defects in the precore region. A point mutation from guanine to adenine at nucleotide 83, converting codon 28 for tryptophan (TGG) to a stop codon (TAG), was the commonest, and it was found in all 113 clones from 7 cases. The remaining case displayed 1 clone with this point mutation and 10 clones with an insertion of 2 base pairs after nucleotide 26. Antibody to hepatitis B core antigen (anti‐HBc) was detected in a high titer in 1 of 10 pilot plasma samples of blood units transfused to this case. HBV DNA clones propagated from it exhibited the same precore‐region defects as those from the recipient. On the basis of these results HBV mutants, defective in the precore region, would appear to be responsible for posttransfusion fulminant hepatitis B, and the exclusion of blood units with high‐titered anti‐HBc would be efficacious in preventing it.

The molecular basis of hepatitis B e antigen (HBeAg)-negative infections

Hepatitis B e antigen (HBeAg)‐negative infections are an unusual form of chronic hepatitis B virus (HBV) infection in which viral replication and liver damage persist despite antibodies against HBeAg. This form of HBV may be associated with fulminant hepatitis. The molecular basis for an HBeAg‐minus phenotype has been extensively studied and is most often a result of mutations in the precore region. However, other mutations can give rise to this phenotype and their investigation and characterization may reveal new insights into the pathogenesis of chronic viral hepatitis.

Genotype dependence of hepatitis C virus antibodies detectable by the first-generation enzyme-linked immunosorbent assay with C100-3 protein.

Hepatitis C virus (HCV) samples in 155 sera, from patients with chronic non-A, non-B liver disease and blood donors, were grouped into four genotypes (I, II, III, and IV) by amplification of core-gene sequences by polymerase chain reaction with type-specific primers. HCV genotypes were compared with various HCV-associated antibodies detectable by the first-generation ELISA (ELISA-1) with C100-3 protein and a second-generation immunoblot assay with four recombinant HCV proteins. Antibodies to C100-3 protein and those to its subsequence (5-1-1) were detected in 13 (93%) and 12 (86%), respectively, of 14 sera with genotype I HCV; 56 (79%) and 58 (82%) of 71 sera with genotype II; 13 (34%) and 6 (16%) of 38 sera with genotype III; and 11 (34%) and 4 (13%) of 32 sera with genotype IV. Amino acid sequences of C100-3 of genotype I HCV are conserved by approximately 90% in genotype II, but only by approximately 75% in genotypes III and IV. The sensitivity of ELISA-1, therefore, would be influenced by heterogeneity in C100-3 sequences of different genotypes.

The entire nucleotide sequences of two distinct TT virus (TTV) isolates (TJN01 and TJN02) remotely related to the original TTV isolates

Summary.u2002TT virus (TTV) has a wide range of sequence divergence by which it is classified into at least 16 genotypes. A TTV isolate of genotype 12 (TJN01) and another of genotype 13 (TJN02) were sequenced in the entire genome, and compared with the reported TTV isolates. TJN01 and TJN02 had genomic lengths of 3787 and 3794 nucleotides (nt), respectively, which were shorter by 66 and 59u2009nt than the prototype TTV isolate of genotype 1 (TA278). TJN01 and TJN02 shared the nucleotide sequence with TA278 merely in 53.9% and 55.2%, respectively. They possessed two major open reading frames (ORFs) and the noncoding region with a GC-rich region forming stem-loop structures, which are characteristic of TTV. However, their amino acid sequences in ORF1 were similar to that of TA278 in only 35.4 and 34.0%, respectively; TJN01 was 45.4% similar to TJN02. Comparison with TTV isolates of the same genotype identified hypervariable regions in ORF1 of TJN01 and TJN02, as in the prototype TTV of genotype 1. However, quasispecies were barely observed in them. Furthermore, sequences of hypervariable regions scarcely changed during 2–5.5 years in both TJN01 and TJN02. These results indicate that TTV of genotypes 12 and 13 are much different from the prototype TTV of genotype 1.

Radioiodinated soluble HL-A antigens: HL-A alloantigenic characterization and use in radioimmunoassay☆

Abstract A method is decribed for the quantitative radioimmunoassay of HL-A antigens which is based on the degree of inhibition of the direct binding of radiolabeled soluble HL-A antigen and its alloantibody by the sample to be assayed. The assay is easily carried out, the results are highly quantitative and reproducible. The method can be applied to the quantitation of HL-A antigens in the insoluble from including those on intact cells as well as in the soluble form. The method has an advantage over the cytotoxic method since it does not require viable cells and complement for the primary test system. The radiolabeled HL-A antigens are prepared by radioiodinating purified, soluble HL-A antigens isolated from human lymphoid cells in long-term culture. The radiolabeled HL-A antigens show high binding activities with the corresponding alloantisera. The degree of binding is determined by precipitating the radioactive HL-A antigen-alloantibody complex with goat anti-human IgG antibody, i.e., the double antibody technique.

Infection by an unenveloped DNA virus associated with non‐A to ‐G hepatitis in Japanese blood donors with or without elevated ALT levels

BACKGROUND: An unenveloped, single‐stranded DNA virus named TT virus has been found in association with elevated alanine aminotransferase (ALT) levels in recipients of transfusions and has been detected frequently in patients with acute or chronic hepatitis of non‐A to ‐G etiology in Japan. DNA of the TT virus was searched for in blood donors with or without elevated ALT levels.

Membranous glomerulonephritis mediated by renal tubular epithelial antigen-antibody complex

Abstract Autologous renal tubular epithelial antigen was demonstrated together with immunoglobulins and β 1 c along the glomerular capillary walls in 4 out of 9 patients with idiopathic membranous glomerulonephritis, and the existence of the clinical entity of glomerulonephritis mediated by tubular epithelial antigen-antibody complexes was suggested. Although no differences in laboratory data were noted between tubular antigen-positive and -negative groups, clinical remission occurred only in the negative group. The fact that no remission was observed in the tubular antigen-positive group may be explained by the continuous supply of the antigen from endogenous sources that maintained the production of immune complexes and subsequent glomerular injury.

Factors Influencing Postexposure Immunprophylaxis of Hepatitis B Virus Infection With Hepatitis B Immune Globulin

Hepatitis B immune globulin was given intramuscularly to 102 staff members of a dialysis unit within 48 h after the accidental needlestick exposure to blood containing hepatitis B surface antigen (HBsAg). Hepatitis B virus (HBV) infection developed in 11 of 56 persons (20%) who had been exposed to blood containing hepatitis B e antigen (HBeAg). Among 56 HBeAg-positive inocula, HBsAg-associated deoxyribonucleic acid polymerase activity in the 11 inocula that transmitted HBV infection was significantly higher than that in the remaining 45 inocula that did not (log counts per minute 3.27 ± 0.57 vs. 2.09 ± 1.19, p p p