W.T. Cooke

HISTOCOMPATIBILITY ANTIGENS ASSOCIATED WITH ADULT CŒLIAC DISEASE

Abstract The histocompatibility (HL-A) antigen phenotype of 49 patients with adult coeliac disease (A.C.D.) was studied; HL-A1 occurred in 78 % and HL-A8 in 88% of A.C.D. patients, compared with 33·2% and 29·5%, respectively, in a control population of 268 individuals; the frequency of the combination HL-A1 plus HL-A8 in A.C.D. patients was 75%, compared with 20·1% in the controls. The difference in each instance was highly significant. It is suggested that this difference in frequency of HL-A antigens found in A.C.D. patients may be related to the aetiology of A.C.D.

Coeliac disease, gluten-free diet, and malignancy.

Two hundred and two patients with coeliac disease or idiopathic steatorrhoea previously reported from this unit have been reviewed after a further 10 years of follow-up. Of 20 more deaths, 10 were due to malignancy. A separate study was made of all patients with histologically confirmed coeliac disease seen to the end of 1972 and followed up to the end of 1974. Twenty-one of the 43 deaths in this series were due to malignant tumours, of which 13 were reticulum cell sarcomas. There was no evidence that patients showing sub-optimal clinical response to gluten withdrawal or persisting falt jejunal biopsies were more prone to die of cancer. A gluten-free diet did not appear to be effective in preventing malignant complications, but a longer follow-up of patients will be necessary to provide a final answer to this question.

Oral manifestations of Crohn's disease.

In a systematic study of 100 patients with Crohns disease, 100 with ulcerative colitis, and of 100 normal subjects matched for age, sex, and denture status, nine patients with Crohns disease, two with ulcerative colitis, and one normal control were found to have oral lesions. In Crohns disease, the macroscopic and histological appearances resembled those encountered elsewhere in the gastrointestinal tract and their incidence was related to the activity of the disorder. The lesions in the other two groups were different macroscopically and histologically. Production of salivary IgA was found to be reduced in Crohns patients with active bowel disease. It is suggested that the occurrence of oral lesions in patients with Crohns disease might represent a local immunological reaction to oral antigens.

Malignancy in Crohn's Disease

In a series of 295 patients with Crohns disease, observed malignancy of the gastrointestinal tract was in excess of expectation. The small intestine and the pancreas were the sites where the excess was statistically very significant.

SERUM-IMMUNOGLOBULINS IN ADULT CŒLIAC DISEASE

Abstract Serum-levels of IgG, IgA, IgM, and Summary IgD have been determined in 110 patients with adult cœliac disease and compared with levels in 152 healthy controls. Significant increases in IgA were found, and these seem to be related to the quantity of gluten ingested and, in some patients, to milk sensitivity. 3 patients with progressive increase in IgA values developed gastrointestinal lymphoma. Significantly low IgG and IgM values were also noted; there was little change on gluten withdrawal.

Coeliac Disease, Fertility, and Pregnancy

The effect of coeliac disease and its treatment on fertility and pregnancy in 74 patients is reported. Those on a normal diet had a shorter reproductive period, were relatively infertile, and had a higher incidence of spontaneous abortions than those on a gluten-free diet. Although maternal health did not appear to be seriously impaired by pregnancy in undiagnosed coeliacs, those on a gluten-free diet had significantly fewer symptoms and had heavier babies.

SECRETORY IgA IN THE SERUM

Abstract With the use of an antiserum specific for secretory piece, secretory IgA has been identified in serum. It was found in 21 (41%) of 52 patients with untreated adult cœliac disease, 5 (13%) of 38 patients with regional enteritis, and 5 (22%) of 23 patients with ulcerative colitis. It was also found in 9 (9%) of 101 healthy control subjects.

HISTOCOMPATIBILITY ANTIGENS IN PATIENTS WITH INFLAMMATORY-BOWEL DISEASE

Abstract The histocompatibility (HL-A) antigen phenotypes of 48 patients with ulcerative colitis (u.c.) and 56 patients with Crohns disease (C.D.) were studied. In U.C. there was a significantly increased frequency of HL-A 11 and HL-A 7 and a reduced frequency of HL-A 3. In C.D. the frequency of HL-A 9 was significantly reduced. The differences in frequency of HL-A antigens found in U.C. and C.D. suggest involvement of genetic factors in inflammatory-bowel disease and could be related to the patients immunological reactivity.

Cellular infiltrate of jejunal biopsies in adult coeliac disease in relation to gluten withdrawal

A comparison has been made of inflammatory cell counts in the lamina propria and epithelium of jejunal biopsies in 11 patients with adult coeliac disease with those found in 12 control subjects. In the coeliac patients, there were significant increases in the numbers of total cells, plasma cells, and intraepithelial lymphocytes, but a significant reduction in lamina propria lymphocytes. Following clinical improvement on a strict gluten-free diet, significant changes in cell counts occurred, but with the exception of lymphocytes in the lamina propria, the counts were still abnormal. Analysis of five patients in whom the biopsy improved to near normal morphology and of six in whom there was no such improvement showed that significant falls in plasma cells and rises in lymphocytes in the lamina propria could occur without improvement in other morphological appearances. These results seem relevant to the problem of diagnosing coeliac disease in patients who, on gluten withdrawal, show an unequivocal clinical response, but no gross morphological improvement in the jejunal biopsy. On the basis of the observed changes in cell counts, there seems little justification in questioning the diagnosis of coeliac disease in such patients.

Inheritance and influence of histocompatibility (HL-A) antigens in adult coeliac disease.

In a study of histocompatibility antigens in adult coeliac disease the HL-A phenotypes have been determined in 117 patients and 149 of their first-degree relatives, of whom 94 had had a jejunal biopsy performed. There was an increased frequency of the HL-A 8 antigen in the patients and their relatives. Family studies showed no irregularity in the inheritance of both this antigen and the HL-A 1 and 8 haplotype.