53

rejection episode needing treatment during the first postoperativemonth (controls vs UDCA treated group, p < 001, Fisher’s exact

test). Patients have been followed for a median of 5 months (range3-8) and controls for 12 months (range 3-15 months).Aminotransferases were significantly lower in the UDCA-treatedpatients than in controls 1 month after transplantation (table).The lack of acute rejection in the UDCA treated liver transplant

recipients cannot be explained by improved surgical techniquesince the liver transplant programme and the surgeons in our unithave not changed since 1985. In addition, the immunosuppressionprotocol remained the same throughout 1989.We used UDCA to achieve a less toxic bile acid pool which would

protect the hepatocytes and prevent cholestasis.1-5 UDCA has adirect protective effect on hepatocytes in both in-vivo and in-vitrostudies.’ Calmus and coworkers’ have shown that UDCA reducesclass 1 HLA-antigen expression on hepatocytes in patients withprimary biliary cirrhosis. HLA class 1 antigens are not usuallyexpressed on the hepatocytes,8 but this effect of UDCA indicatesthat it may also have other immunoeffects and the potential to alterantigen expression in cells other than hepatocytes in such patients.

Department of Surgery,Sahlgrenska Hospital,University of G&ouml;teborg,S-413 45 G&ouml;teborg, Sweden

HANS PERSSON

STYRBJ&Ouml;RN FRIMANTORE SCHERST&Eacute;N

JOAR SVANVIKINGVAR KARLBERG

1. Poupon R, Chretien Y, Poupon RE, Ballet F, Calmus Y, Darnis F. Is ursodeoxycholicadd an effective treatment for primary biliary cirrhosis? Lancet 1987; i: 834-36.

2. Ullrich D, Rating D, Schr&ouml;ter W, Hanefeld F, Bircher J. Treatment withursodeoxycholic acid renders children with biliary atresia suitable for liver

transplantation. Lancet 1987; ii; 1324.3. Ghezzi C, Zuin M, Battezzati PM, Podda M. Effects of ursodeoxycholate, taurine and

ursodeoxycholate plus taurine on serum enzyme levels m patients with chronichepatitis. Hepatology 1987; 7: 1110.

4. Nittons H, Tokita A, Hayashi M, el al. Ursodeoxycholic acid therapy in the treatmentof biliary atresia. Biomed Pharmacother 1989; 43: 37-41.

5. O’Brien C, Senior JR, Batta AK, et al. Ursodeoxycholic acid treatment producesmarked clinical and biochemical amelioration of primary sclerosing cholangitis.Gastroenterology 1989; 96: 640.

6. Heuman DM, Komito SF, Pandak WM, Hylemon PB, Vlahcevic ZR.

Tauroursodeoxycholic acid protects against cholestatic and hepatocytolytic toxicityof more hydrophobic bile salts. Gastroenterology 1989; 96: A607.

7. Calmus Y, Gane P, Rouger P, Poupon R. Hepatic expression of class I and class IImajor histocompatibility complex molecules in primary biliary cirrhosis: effect ofursodeoxycholic add. Hepatology 1990; 11: 12-15.

8. Rouger PH, Poupon R, Gane P, Mallissen B, Darnis F, Salomon CH. Expression ofblood group antigens including HLA markers in human adult liver. Tissue Antigens1986; 27: 78-86.

Meningococcal disease: high virulence andlow transmission

SiR,&mdash;Dr Knight and his colleagues (May 19, p 1182) suggest thatthe prolonged outbreak of meningococcal disease in the Gloucesterarea and in Plymouth might be due to local environmental factors, agenetically susceptible population, or a more virulent strain of theorganism. Their evidence indicates that isolates from patients inthese two areas are from a single clone, a sulphonamide-resistant,serogroup B, serotype 15, serosubtype PI.16 strain of Neisseriameningitidis (B 15/16 R). They suggest that this strain has remainedlocalised in these regions because it is of increased virulence butpoorly transmissible.

Individuals who are genetically incapable of secreting thewater-soluble form of their ABO blood group antigens (non-secretors) are significantly over-represented among patients withmeningococcal disease1 and among carriers of meningococci.1 Weshowed a significant increase in the proportion of non-secretors inStonehouse, the Gloucestershire town where there has been anunusually high attack rate of disease due to the B15/16R strain,3.4and in a Scottish school population in which there was an outbreakdue to a serogroup B, serotype 4, serosubtype P1.15, sulphonamide-resistant strain (B4/15R).2

100 individuals from the Plymouth area were examined for theirLewis blood group antigen as controls for a study of the Lewisphenotype among patients with breast cancer.5 Non-secretors can

PREVALENCE OF NON-SECRETORS IN THREE BRITISHPOPULATIONS IN WHICH OUTBREAKS OF MENINGOCOCCAL

DISEASE OCCURRED

express only Lewisa and secretors express Lewisb. If the controls arerepresentative of the Plymouth population, the proportion ofLewisa/non-secretors is significantly higher (37-6%) than that ofblood donors in the south west region (chi-squared test p < 0-0005;table).

In addition to the hypothetical increased virulence and poortransmissibility of the B15/16R clone, we suggest that the higherproportion of the genetically susceptible non-secretors in the twoareas might contribute to the localisation of these outbreaks.

Department of Bacteriology,Medical School,University of Edinburgh,Edinburgh EH8 9AG, UK

C. C. BLACKWELLD. M. WEIR

1. Blackwell CC, Jonsdottir K, Hanson M, et al. Non-secretion of ABO antigenspredisposing to infection by Neisseria meningitidis and Streptococcus pneumoniae.Lancet 1986; ii: 284-85.

2. Blackwell CC, Weir DM, James VS, et al. Secretor status, smoking and carriage ofNeisseria meningitidis. Epidemiol Infect 1990; 104: 203-09.

3. Blackwell CC, Weir DM, James VS, Cartwright KAV, Stuart JM, Jones DM. TheStonehouse study: secretor status and carriage of Neisseria species. Epidemiol Infect1989; 102: 1-10.

4. Stuart JM, Cartwright KAV, Jones DM, et al. An outbreak of meningococcal diseasein Stonehouse: planning and execution of a large scale survey. Epidemiol Infect1987; 99: 579-89.

5. Phipps RF, Perry PM. Lewis-negative genotypes and breast cancer. Lancet 1989; i:1198-99.

DNA probes for typing Neisseriameningitidis

SIR,-We were most interested in the use of a DNA probe toinvestigate genetic. heterogeneity among Neisseria meningitidisB15P1.16 strains, described by Dr Knight and colleagues (May 19,p 1182). They used a probe that detects a small (2 kb) repeatedsequence and we are not certain that the results obtained using thisprobe are epidemiologically valid. The B15P1.16 sulphonamide-resistant strains that are prevalent in the UK and elsewhere havebeen shown to be clonally related by isoenzyme electrophoresis butit is reasonable to expect that there are degrees of geneticheterogeneity within this clone that will be large enough to code forvariations in surface components and possibly virulence factors. Wehave been using a randomly selected probe prepared from agenomic library of B15P1.16 prepared in ^ W es&Agrave;B phage to typemeningococci by restriction fragment length polymorphisms(RFLPs). This probe appears to react with all meningococci that wehave tested and has a high degree of discrimination and

reproducibility. When we applied this probe to B15P1.16 strainscollected over the past decade from many parts of the UK weobtained results that differ from those of Knight et al and lead to afundamentally different interpretation. In short, we find that thereare two main variants of the B 15P 1.16 strains scattered about theUK and that the Plymouth strains have a different RFLP pattern tothe Gloucester strains. The difference is demonstrable in isolatesfrom 1982 and has remained stable and detectable through to the1990 isolates.We have also had the opportunity to use a monoclonal antibody

(prepared by Dr J. E. Heckels, Southampton) that detects a pointmutation in the class I outer membrane protein P1.16 on theB15P1.16 isolates. With this entirely different approach the