1346

suggest that antibody to SOD may contribute to the false-positive experienced with the Ortho HCV ELISA.

results

YUSEI IKEDA GOTARO TODA NAOAKI HASHIMOTO KIYOSHI KUROKAWA

First

Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113, Japan 1. Kuo

G, Choo Q-L, Alter HJ, et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 1989; 244: 362-64. 2. Ikeda Y, Toda G, Hashimoto N, et al. Anticalmodulin antibody in liver diseases: a new antibody against a cytoskeleton-related protein. Hepatology 1987; 7: 285-93. 3. Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci (USA) 1979; 76: 4350-54.

False-positive anti-HCV tests in rheumatoid arthritis SIR,-Besides the presence of antibodies to hepatitis C virus (anti-HCV) in sera from patients with post-transfusional hepatitis, a high prevalence of these antibodies has been reported in sera from patients with various liver diseases—eg, primary biliary cirrhosis, cryptogenic cirrhosis, and autoimmune hepatitis.1,2 With a commercial ELISA (Ortho Diagnostics) we occasionally found anti-HCV in sera from patients who did not have risk factors for HCV infection or evidence of liver disease. Some of these patients, however, had a positive rheumatoid factor. To clarify these findings further we studied selected patients with a clinical diagnosis of rheumatoid arthritis (RA) and positive rheumatoid factors for the presence of anti-HCV. The group consisted of 13 male and 28 female patients (mean age 54-3 years, SD 11-9) with RA. All patients had normal serum

aspartate aminotransferase and alanine aminotransferase concentrations and no history of transfusion of blood products or illicit drug abuse. 9 patients were positive for anti-HBc and anti-HBs, indicating previous hepatitis B virus infection. All patients had a rheumatoid serum factor of over 50 IU/ml (range more than 50 to 3200, normal less than 30 IU/ml) measured by the rheumatoid factor latex test (’Rapitex RF’; Behring, Marburg, FRG). 29 of these patients were also positive (over 12.55 lU/ml, normal less than 125 IU/ml) with the Waaler Rose test (’Cellognost RF Micro’; Behring). The anti-HCV test was positive in 25 (61 %) patients. The same results were obtained on repeat testing next day, whereas healthy, rheumatoid-factor negative controls remained negative. No correlation between level of rheumatoid factor and positive anti-HCV test was observed. Since all patients had normal liver function tests and did not belong to risk groups, previous or existing HCV infection seems very unlikely. We conclude that positive anti-HCV tests in patients without evidence of liver disease and with autoimmune disease must be regarded with caution. Sera from such patients should be evaluated further for the presence of rheumatoid factors.

Department of Internal Medicine, University of Heidelberg, D-6900 Heidelberg, West Germany

L. THEILMANN M. BLAZEK T. GOESER K. GMELIN B. KOMMERELL W. FIEHN

1. Bruix J, Barrera

JM, Calvet X, et al. Prevalence of antibodies to hepatitis C virus in Spanish patients with hepatocellular carcinoma and hepatic cirrhosis. Lancet 1989;

ii: 1004-06. 2. Esteban JJ, Esteban R, Vilandomiu L, et al. groups in Spain. Lancet 1989; ii: 294-97.

Hepatitis C virus antibodies among risk

Recombinant immunoblot assay for hepatitis C antibody SIR,-We need a test to confirm a positive ELISA (Ortho Diagnostic Systems) for hepatitis C antibody, especially in the

setting of blood transfusion.1-3 Transfusion centres will not want to implement screening and subsequent counselling without confirmation, and reference diagnostic laboratories will be unwilling

to report results without a confirmatory test. The recombinant immunoblot assay (RIBA) developed by Chiron/Ortho may be just such a test. The assay is based on the recombinant antigens used in the ELISA with, in addition, low and high IgG control bands. The antigens are immobilised on nitrocellulose strips which, after incubation with serum or controls, are washed and reacted with goat anti-human IgG labelled with horseradish peroxidase. Addition of 4-chloro-l-naphthol solution results in blue/black bands where labelled peroxidase is present. We have used a small number of these RIBA strips and our experience suggests that caution may be needed when interpreting a positive ELISA for anti-HCV. Unfortunately, supplies of these RIBA strips are limited. Of 14 blood donor sera which were repeatedly reactive in the ELISA only 4 were positive by RIBA. 3 of these donors were also seropositive for hepatitis B core antigen, and 2 of the 3 had raised alanine aminotransferase (ALT) levels at the time of testing. 3 RIBA-negative donors have given positive ELISA results on follow up sera, although none of the RIBA-negative sera were hepatitis B virus core antibody positive or had a raised ALT. Several sera showed weak reaction on the C100-3 lines although not as intense as the low IgG control, which is the criterion for positivity. The prevalence of anti-HCV amongst healthy blood donors may be lower than originally indicated. Sera from 4 patients with liver disease and 1 with jaundice after multiple transfusions, which were repeatedly ELISA positive, were also RIBA negative. However, 3 sera from patients with haemophilia showed a strong reaction on both HCV antigen lines. This validates previous findings on these patients.4 1 patient with liver disease and reported parenteral exposure was also positive in both test systems. In high-risk groups, therefore, the predictive value of the ELISA test is higher than it is in blood donors.

I thank Drs F. Ala, E. Elias and Barbara for discussion.

J. Pasi for supplying samples and Dr J.

Regional Virus Laboratory, East Birmingham Hospital, Birmingham B9 5ST, UK

SUSAN SKIDMORE

1. Connreras M, Barbara J. Screening for hepatitis C virus antibody. Lancet 1989; ii: 505. 2. Cash JD, McClelland DBL, Urbaniak SJ, Brookes E, Follett EAC. Screening for hepatitis C virus antibody. Lancet 1989; ii: 505. 3. Flegg PJ. Ethics of screening for hepatitis C virus. Lancet 1989; ii: 1221. 4. Skidmore SJ, Pasi KJ, Mawson SJ, Williams MD, Hill FGH. Serological evidence that dry heating of clotting factor concentrates prevents transmission of non-A, non-B hepatitis. J Med Virol 1990; 30: 50-52.

CNS demyelination associated with diploid cell rabies vaccine SIR,-Since the human diploid cell rabies vaccine (HDCV) was introduced in 1980 there have been three reports of neuroparalytic illness associated with it.1-3 These neurological deficits were restricted to the peripheral nervous system and presented as a Guillain-Barre-like illness. A 25-year-old veterinarian received the first two intramuscular injections of 1 ml HDCV for pre-exposure immunisation on July 19 and Aug 3, 1987 (Merieux lot no Z 0108, expiry date Feb 8, 1988). On Aug 11 she noted weakness in her right leg, followed by clumsiness with her right hand. She had had a brief shaking chill before the onset of symptoms. Neurological examination revealed mild weakness of the right arm, hand, and leg with right-arm and patellar hyperreflexia, and an equivocal plantar extensor response on the right. No cranial nerve, cerebellar, or sensory deficits were detected. A computerised tomographic (CT) scan was normal but a single dose, non-delayed contrast CT study revealed a small focus of enhancement near the anterior horn of the left lateral ventricle, and magnetic resonance imaging (MRI) indicated increased signal intensity in the periventricular regions bilaterally. Cerebrospinal fluid examination demonstrated: total protein 21.4mg/dl with four ratio 0-545 (0-47 in serum), IgG index 11 (normal below 0-66), cultures negative for bacteria and fungi, myelin basic protein 1-1ng/dl (normal). Her serum rabies antibody titre was above 0-5 IU/ml. Evoked responses were normal. Serum protein electrophoresis revealed a polyclonal increase in IgG

oligoclonal bands, IgG/albumin

(1800 mg/dl).