1162 LOW FREQUENCY OF CHLAMYDIAL ANTIBODIES IN PATIENTS WITH CROHN’S DISEASE AND ULCERATIVE COLITIS D. TAYLOR-ROBINSON B. J. THOMAS

C. A. O’MORAIN A. J. LEVI

Medical Research Council Clinical Research Centre and Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ

Serum samples from 55 patients with Crohn’s disease and from 23 patients with ulcerative colitis were tested for antibodies to Chlamydia trachomatis immunotypes by a micro-immunofluorescence technique. Antibody titres of 1:8 or greater against several immunotypes were detected in 14·5% of patients with Crohn’s disease and in 21·7% of those with ulcerative colitis. These figures resemble the incidence in a healthy, non-venereal-disease population. Furthermore, there was no correlation between the presence of antibody and such factors as duration of symptoms, localisation of disease, or disease activity. These findings indicate that there is no reason to believe that Crohn’s disease involves chlamydiae or that examination for chlamydial antibody is helpful in diagnosis.

Summary

Introduction INFECTIOUS agents, particularly viruses and cell-walldeficient variants of bacteria,2-6 have been implicated in the aetiology of inflammatory bowel disease. In addition, homogenates of diseased tissue have been reported to produce in animals a granulomatous response similar to Crohn’s disease,.7-9 Lymphogranuloma venereum (L.G.V.) is a sexually transmitted disease which is also characterised by granuloma formation and is caused by three _immunotypes (LI, 2, and 3) of Chlamydia trachomatis. Schuller et al.10 reported the occurrence of antibody directed specifically against the L.G.v. immunotypes of C. trachomatis in sera of 69% of patients with Crohn’s disease. We examined sera from patients with Crohn’s disease and ulcerative colitis for antibody to immunotypes of C. trachomatis and obtained quite different results. TABLE

I-C. trachomatis

Materials and Methods Serum samples were collected from 55 patients with Crohn’s disease, diagnosed by characteristic histological lesions or typical clinical and radiological features, and from 23 patients with ulcerative colitis, diagnosed by characteristic histological appearances. Other features of the patients and of these diseases are shown in table II. A patient was regarded as having active disease if admission to hospital was required. A simplified micro-immunofluorescence (micro-i.F.) technique"was used to test the sera for antibody to C. trachomatis immunotypes B, D/E, F/G, H/I, J and Ll, and 2 and 3. These antigens were prepared from chlamydiae grown in embryonated hens’ eggs.

Results C. trachomatis at a titre of 1:8 or greater detected in sera from 8 of 55 (14.5%) patients with Crohn’s disease and from 5 of 23 (21.7%) patients with ulcerative colitis (table I). Only 1 patient had a serum antibody titre as high as 1:64. In no case was antibody directed specifically against the L1, 2, and 3 immunotypes of L.G.v. There were cross-reactions (shown in table I for antibody titres of 16 or greater) with most of the other five single or composite immunotypes used in *he test. Patients with antibody were mainly below the age of forty years (table n). There was no evidence that the occurrence of antibody in inflammatory bowel disease was related to duration of symptoms or that it was particularly associated with small-bowel involvement or with active as opposed to inactive disease (table n). Five patients with inflammatory bowel disease had an associated arthritis; of these, 2 of 4 with Crohn’s disease and 1 with ulcerative colitis had antibody at a titre of 1:8

Antibody to

was

only. Discussion We found antibody types at a titre of 1:8 TABLE II-RELATION OF

CROHN’S

PATIENTS WITH

Cross-reactions

DISEASE AND ULCERATIVE

against individual immunotypes

not

shown for these

3 patients. t Each column of figures shows reciprocal antibody titres immunotypes for one patient.

to

the C. trachomatis immunogreater in 14.5% of patients

SEX, AGE,

CROHN’S

COLITIS

*

or

AND ACTIVITY TO OCCURRENCE OF

ANTIBODY MEASURED BY MICRO-I.F. IN

SERUM OF PATIENTS WITH

to

indicated *

Titre of 8 or more.

AND DISEASE LOCALISATION

C. trachomatis ANTIBODY IN

DISEASE AND ULCERATIVE COLITIS

1163 with Crohn’s disease and in 21.7% of those with ulcerative colitis, a frequency similar to that seen in a nonpromiscuous, non-venereal-disease population.12 In contrast, antibody to C. trachomatis has been found by us" and by othersl4 in more than 50% of men with nongonococcal urethritis (N.G.U.) and in over 70% of women with cervicitis from whom chlamydiae were isolated. 14 Furthermore, about half the men in whom reactive arthritis develops after N.G.u. have higher titres of antibody than those with uncomplicated N.G.U. 12 However, we did not detect antibody, or found it only in low titres, in the sera of patients who had arthritis associated with either Crohn’s disease or ulcerative colitis. None of the patients with inflammatory bowel disease who had antibody had distinguishing clinical or pathological features. There was, for example, no particular association of antibody with small-bowel involvement in Crohn’s disease to suggest that antibody had developed as a result of passage of chlamydiae across a diseased small-bowel wall. The few patients with antibody were predominantly in the sexually active period of life, a finding which is compatible with a previous chlamydial genital infection. If chlamydiae were involved in initiating inflammatory bowel disease, antibody production would probably be most stimulated in the early stage of disease or during acute exacerbations. However, although exact determination of the initial onset of Crohn’s disease is impossible, the facts that antibody was absent from many of our patients who had early disease, and that most of those who had antibody did not have active disease, suggest to us that chlamydiae are not involved. Our results are not compatible with those of Schuller et a1.lO who reported chlamydial antibodies to the L.G.v. immunotypes in 69% of patients with Crohn’s disease. The possibility that their patients were particularly sexually promiscuous and that most had had L.G.V. or a non-L.G.v. genital chlamydial infection seems unlikely. If they had, chlamydial antibody would not have been confined to the L.G.V. immunotypes, as was reported. Furthermore, the fact that Crohn’s disease is relatively common in Europeans and rare in Africans,15 while the reverse is seen for L.G.v., does not accord with the idea that Crohn’s disease might be a manifestation of L.G.V. Difficulties may occasionally arise with the performance of the micro-LF. test, particularly with the reading of results. We were intrigued by the report of the Dutch workerslO that their test detected antibody only to the Ll-3 immunotypes. Such specificity seems remarkable since antibody strictly confined to these immunotypes is not seen even in patients with L.G.v.l6 and in our tests on sera from patients with inflammatory bowel disease we found cross-reactions with several immunotypes of C. trachomatis. Whatever the explanation for the differences in results, our results do not lead us to believe that chlamydiae are important in the pathogenesis of Crohn’s disease. Of course, Schuller et al. 10 did not consider that they could necessarily interpret their findings in this way. They did suggest, however, that the presence of antibody in Crohn’s disease patients might reflect passage of antigen non-specifically across a damaged small bowel and that the antibody test is helpful in distinguishing Crohn’s disease from other inflammatory bowel diseases. Our failure to find antibody more frequently in serum from patients with Crohn’s disease than in serum from patients with ulcerative col-

itis does not, however, support the idea that detection of chlamydial antibody is helpful in diagnosis. Requests

for

reprints

should be addressed

to

D. T.-R.

REFERENCES

L., Phillips, C. A., Little, P. K., Roessner, 1. Whorwell, J., Beeken, K. D. Lancet, 1977, i, 1169. 2. Parent, K., Mitchell, P. D. Gastroenterology, 1976,71,365. 3. Parent, K., Mitchell, P. D. ibid. 1977,72, 1111. 4. Burnham, W. R., Stanford, J. L., Lennard-Jones, J. E. Gut, 1977, 18, 965. 5. White, S. A., Nassau, E., Burnham, W. R., Stanford, J. L., Lennard-Jones, J. E. ibid. 1978,19,443. 6. Burnham, W. R., Lennard-Jones, J. E., Stanford, J. L., Bird, R. G. Lancet, 1978, ii, 693. 7. Mitchell, D. N., Rees, R. J. W. ibid. 1970, ii,168. 8. Cave, D. R., Kane, S. P., Mitchell, D. N., Brooke, B. N. ibid. 1973, ii, 1120. 9. Cave, D. R., Mitchell, D. N., Brooke, B. N. Gastroenterology, 1975, 69, 618. 10. Schuller, J. L., Veeken, I. V. D., Ulsen, J. P.-V., Michel, M. F., Stolz, E. Lancet, 1979, i, 19. 11. Thomas, B. J., Reeve, P., Oriel, J. D.J. clin. Microbiol., 1976,4,6. 12. Holmes, K. K., Handsfield, H. H., Wang, S.-P., Wentworth, B. B., Turck, M., Anderson, J. B., Alexander, E. R. New Engl. J. Med., 1975, 292, P.

W.

1199. 13. Keat, A. C., Thomas, B. J., Taylor-Robinson, D., Maini, R. N., Scott, J. T., Pegrum, G. D. Ann. rheum. Dis. (in the press). 14. Treharne, J. D., Dines, R. J., Darougar, S. in Non-gonococcal Urethritis and Related Infections (edited by D. Hobson and K. K. Holmes); p. 249. 15. 16.

Washington, D.C., 1977. Lewkonia, R. M., McConnell, R. B. Gut, 1976,17,235. Wang, S.-P., Grayston, J. T., Kuo, C.-C., Alexander, E. R., Holmes, K. K. in Non-gonococcal Urethritis and Related Infections (edited by D. Hobson and K. K. Holmes); p. 237. Washington, D. C., 1977.

CELLULAR ORIGINS OF THE FETAL-HÆMOGLOBIN-CONTAINING CELLS OF NORMAL ADULTS CHRISTOPHER BUNCH

W. G. WOOD

D.

J. WEATHERALL Nuffield Department of Clinical Medicine, University of Oxford, Radcliffe Infirmary, Oxford, U.K.

J. W. ADAMSON Veterans Administration Hospital, Seattle, Washington, U.S.A.

The origin of the small population of adult red cells which contain Hb F (F-cells) has been studied in a clonal disorder of hæmopoiesis, polycythæmia rubra vera (P.R.V.). In eleven patients who had not received cytotoxic therapy F-cells comprised

Low frequency of chlamydial antibodies in patients with Crohn's disease and ulcerative colitis.

1162 LOW FREQUENCY OF CHLAMYDIAL ANTIBODIES IN PATIENTS WITH CROHN’S DISEASE AND ULCERATIVE COLITIS D. TAYLOR-ROBINSON B. J. THOMAS C. A. O’MORAIN A...
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