Tissue Antigens (1985) 25,4749 Short communication

HLA antigens in ulcerative colitis: a study in the Sicilian population CALOGERO CARUSO‘, PATRIZIA PALMERS’, LORENZO OLIVA’, AMBROG~O ORLANDO’ and MARIO COITONE~

’Servizio di Immunologia Tissutale, Istituto di Patologia generale dell’universita di Palermo and Tattedra di Clinica Medica R dell’Universita di Palermo, Ospedale V. Cervello, Palermo, Italy

HLA antigens were investigated in 41 Sicilian patients with ulcerative colitis and in 151 healthy controls. Frequencies of HLA-B5 and DR2 were increased in the group of patients with ulcerative colitis whereas the DR3 antigen frequency was de- creased. However the corrected p values were not significant. Thus, present results indicate that in ulcerative colitis HLA linked genetic factors play a marginal role, if any.

Received for publication 25 June, revised, accepted 24 September 1984

The current hypothesis for the pathogenesis of Ulcerative Colitis (UC), an inflammatory bowel disease (IBD), involves an interaction between host response, genetic influences and external agents, possibly microbial (Kirsner & Shorter 1982). HLA antigens have been shown to be associated with the response to some microbial antigens (van Eden et al. 1982).

To date, the search for HLA markers in UC has been inconclusive (Kirsner & Shorter 1982). Several surveys did not find divergen- ces from controls (Corazza et al. 1978, Smolen et al. 1982), whereas other authors found significant associations with different antigens in different populations (van den Berg-Loonen et al. 1977, Delpre et al. 1980, Schrumpf et al. 1982). Recently, in a Japanese population, an association with B5, DR2 ha- plotype has been shown (Asakura et al. 1982).

It is interesting that this haplotype appears to be associated with a low immune responsive- ness to several infectious antigens (see Refer- ences in Dausset & Contu 1980, Kato et al. 1982).

We have studied the possible association between UC and HLA antigens in a homoge- neous Caucasian population by typing 41 Si- cilian patients and 151 healthy Sicilian con- trols. The distribution of antigen frequencies of HLA-A, B, C, DR, MT and MB in patients with UC and in controls are shown in Table 1. Frequencies of B5 and DR2 antigens were in- creased in the group of patients with UC, whereas DR3 antigen frequency was de- creased; however, the corrected p values were not significant.

Haplotype frequencies (HF) and linkage disequilibrium parameter (A) values in con- trols and in patients were calculated by using

48 CARUSO ET AL.

Table I . Frequencies of HLA-A, B, C, DR, M T and M B in 41 patients with ulcerative colitis and in I51 controls.

HLA-A HLA-B and C HLA-DR, MT and MB

Anti- Patients Controls Anti- Patients Controls Anti- Patients Controls gens No. % No. % gens No. % No. % gens No. Yo No. %

A1 A2 A3 Aw23 Aw24 A10 A l l A28 Awl9

13 31.7 36 23.8 17 41.5 61 40.4 6 14.6 32 21.2 3 7.3 17 11.2 6 14.6 29 19.2 4 9.7 16 10.6 8 19.5 25 16.5 6 14.6 5 3.3

16 39.0 53 35.1

BY B7 B8 B12 B13 B14 B15 Bw16 B17 B18 Bw21 Bw22 B27 Bw35 B37 B40 Bw41 Bw53

c w 1 cw2 cw3 cw4

13 31.7 24 15.9 4 9.7 13 8.6 3 7.3 13 8.6 8 19.5 20 13.2 3 7.3 15 9.9 4 9.7 23 15.2 5 12.2 16 10.6 2 4.9 13 8.6 3 7.3 9 6.0 4 9.7 19 12.6 6 14.6 22 14.6 2 4.9 8 5.3 2 4.9 6 4.0

10 24.4 43 28.5 1 2.4 2 1.3 2 4.9 13 8.6 1 2.4 14 9.3 5 12.2 8 5.3

4 9.7 7 4.6 6 14.6 20 13.2 3 7.3 17 11.2

15 36.6 45 29.8

DR1

DR3‘ DR4 DR5 DRw6 DR7 DR8 DRw9

~ ~ 2 3 4 9.8 34 22.5

13 31.7 25 16.6 1 2.4 22 14.6 5 12.2 27 17.9

21 51.2 65 43.0 14 31.7 59 39.1 11 26.8 41 27.1

- 3 2.0 - 1 0.7

- -

MT1 27 65.8 100 66.2 MT2 31 73.2 123 81.5 MT3 14 34.1 66 43.7

MB1 27 65.8 100 66.2 MB2 12 29.3 55 36.4 MB3 25 61.0 95 62.9

~~~~~~ ~ ~ ~~~~

HLA-A, B and C antigens were determined by using the standard microlymphocytotoxicity technique. Typing for HLA-DR, MT and MB specificities was performed by using the two-colour fluorescence test

(van Leeuwen & van Rood 1980). For evaluation of HLA association the chi-square test with Yates continuity correction and Fisher’s exact test were used where appropriate; p < 0.05; ’ p = 0.05;

‘p < 0.02236

the method of Mattiuz et al. (1970). HF in controls was 27 and A was 20 (p < 0.01). On the other hand, HF in patients was 80 and A was 50 (p not significant; that is likely because of the small number of patients studied). However, we could find a higher frequency of phenotype B5 + DR2 in patients with UC than in controls (17% versus 6%, p < 0.06).

Thus in our group of Sicilian patients we have found an increase of B5 and DR2 anti- gens, but this was not significant after correc- tion for the number of antigens tested. There- fore present results indicate that in UC, HLA

linked genetic factors play a marginal role, if any. The importance of HLA linked genetic factors in the Crohn’s disease (CD), the other IBD, instead, has been suggested in previous studies by both population and family ana- lyses (Smolen et al. 1982, Caruso et al. 1983, Cottone et al. 1983).

One concept of genetics of IBDs recognizes UC and CD as prototypes of a single disease process encompassing a variety of intermedi- ate tissue reactions with two polygenic sys- tems determining liability and possessing genes in common. The possession of only a

HLA ANTIGENS IN ULCERATIVE COLITIS 49

few of these genes is assumed to predispose a person to UC whereas a more complete geno- type predisposes to CD (Kirsner & Shorter 1982). Data showing that HLA linked genetic factors play a role in CD but not in UC (Smolen et al. 1982, Caruso et al. 1983, pres- ent results) might be relevant to this hypo- thesis.

Acknowledgments

We would like to thank Prof. Alfredo Salerno for helpful suggestions and criticism. This work was supported by a grant of Minister0 della pubblica Istruzione, Rome (40%, 1982 and 1983). The excellent technical assistance of Mr. Carlo Muratore is appreciated.

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Address: Dr. Calogero Caruso Servizio di Immunologia Tissutale Istituto di Patologia generale dell’Universita Corso Tukory 211 90134 Palermo Italy