M Verkasalo

Intestinal γ/δ receptor-bearing T lymphocytes in celiac disease and inflammatory bowel diseases in children. Constant increase in celiac disease

ABSRACT: We studied the numbers of T-cell receptor α/β- and γ/δ-bearing lymphocytes in 27 jejunal specimens from 19 celiac patients, 27 rectal and colonic specimens from 14 ulcerative colitis patients and four patients with Crohns disease, and 24 control specimens. MAb and a three-layer peroxidase staining method were used. Only low numbers of γ/δ+ cells were seen in normal jejunum and rectum of controls, as well as in the specimens of patients with inflammatory bowel diseases. In the lamina propria of celiac patients, the mean number of γ/δ+ cells was significantly higher than in the controls before treatment, during gluten-free diet, and after the gluten challenge. Within the jejunal epithelium, the number of γ/δ+ cells was elevated before and during gluten elimination and after the challenge test. The absolute number of intraepithelial γ/δ+ cells remained constant during gluten elimination and provocation. We infer that the constantly elevated population of γ/δ+ T cells in the epithelium of celiac patients may play an important role in the pathogenesis of celiac disease.

Changing pattern of cow's milk intolerance. An analysis of the occurrence and clinical course in the 60s and mid-70s.

ABSTRACT. Verkasalo, M., Kuitunen, P., Savilahti, E. and Tiilikainen, A. (Childrens Hospital, University of Helsinki, Finland). Changing pattern of cows milk intolerance. Acta Paediatr Scand, 70: 289, 1981.–The rapid changeover to commercial adapted infant formulae which took place in Finland between 1973 and 1975 was studied as a factor in the occurrence of severe intestinal cows milk intolerance (CMI). Of infants treated for CMI in 1962‐73, ninety‐three percent (25/27) were on homemade or unadapted formulae. The admission rate for CMI in these years was 0.22/1 000 liveborn infants breast fed less than six months. During 1974‐77 the corresponding figure was 0.56, with 85 % of the patients (18/26) on adapted cows milk formulae. The patients treated before 1974 had a longer symptomatic period before admission, greater growth retardation and more severe intestinal damage than those seen during and after 1974. This is believed to reflect mainly the increasing awareness of CMI on the part of both laymen and the medical profession. In the history of 2/3 of the patients at least one of the following conditions was noted: non‐breast feeding, infectious gastroenteritis, praematurity, 21‐trisomy, prior intra‐abdominal surgery, Hirschsprungs disease, and atopic disease in family members. The long follow‐up averaging over four years revealed four patients with coeliac disease. In one of these the proximal jejunal mucosa was normal after two years on gluten‐containing diet, but he showed a mucosal relapse as late as between 2 to 4 years on normal diet.

Clinics of coeliac disease in children in the 2000s

Objective:  To describe the clinical picture of patients with coeliac disease (CD) and the change in its presentation over the past decades.

Undiagnosed silent coeliac disease: A risk for underachievement?

Objective. Silent coeliac disease is reported in 1% of Caucasian populations, but there is a lack of knowledge of its natural course and the risk of complications. The need for population screening is debated. We sought for complications of untreated coeliac disease in a well-defined cohort of Finnish adults. Material and methods. Subjects (n=2427, ages 24–39 years) attending the 21-year follow-up visit of the study “Cardiovascular Risk in Young Finns” completed an extensive questionnaire on their health, diet, social situation and family life, and were given a medical examination. Measurement of serum IgA-transglutaminase and IgA-endomysium antibodies identified 21 subjects with silent coeliac disease. Results. The subjects with silent coeliac disease did not differ from the rest of the cohort in age, gender, stature, weight, medical diagnoses (autoimmune, malignant), health concerns, use of alternative medications, physical activity, or in the cause of death their parents. They had lower serum HDL-cholesterol (1.12 versus 1.29 mmol/L; p=0.015), as described for active coeliac disease. Fewer (5.3% versus 22.8%; p=0.047) had a university or college degree or worked in managerial or professional positions (28% versus 45%; p=0.112). Conclusions. The underachievement in education and working life observed in subjects with silent coeliac disease is a new and intriguing finding and may be related to the increased prevalence of depressive and disruptive behavioural disorders described in teenagers with untreated coeliac disease. Our findings add a new ingredient to the ongoing discussion regarding the need for population screening for silent coeliac disease.

HLA antigens and atopy in children with coeliac disease.

HLA antigens and various aspects of atopy were studied in 42 Finnish children and adolescents with coeliac disease, and the results were compared with findings of recent population studies. The HLA associations were as expected: relative risks for coeliac disease in individuals with HLA-B8, DR3, and DR7 were 8 . 0, 18 . 6, and 15 . 0, respectively. Children with coeliac disease were significantly more often atopic than unselected schoolchildren. Atopy was significantly more frequent and the onset of coeliac disease later for B8/DR3- patients than B8/DR3+ patients. There was no obvious relation between DR7 and atopy. It is concluded that atopy predisposes to coeliac disease partly independently of the HLA-DR3 associated disease susceptibility gene(s), and that different mechanisms may operate in the pathogenesis in coeliac disease patients with and without atopy.

Recent trends in breast-feeding in Southern Finland.

Abstract. Verkasalo, M. (Childrens Hospital, University of Helsinki, Finland). Recent trends in breast‐feeding in southern Finland. Acta Paediatr Scand, 69:89, 1980.—A retrospective study on breast‐feeding (BF) during 1962–77 has been carried out for the province of Uusimaa. The study was based on 35815 child health records kept by community health centres. Information was entered in 76% of the records, the percentage improving from 52 to 94 during the study period. The average duration of BF was observed to decline steadily from 2.3 months in 1962 to 1.7 in 1971, increasing thereafter to 3.6 months by the end of the study. A similar pattern of slow decline turning to a sharp rise by 1971 can be seen in the percentage of mothers beginning BF, and various time categories of nursing. The observed increase in BF is attributed to changing general attitudes, which are influenced by international trends and campaining by health authorities. Social benefits also play a role, as the increase in BF coincides with extensions of maternity leave from 2 to 7 months in the seventies. The results indicate a favourable response to efforts to promote BF and suggest that these efforts should be continued and intensified

Gluten challenge in children with dermatitis herpetiformis: a clinical, morphological and immunohistological study.

Twenty one children with dermatitis herpetiformis were studied in an attempt to evaluate the response in the skin, in jejunal morphology, and in jejunal immunoglobulin containing cell counts to gluten elimination and subsequent gluten challenge. In all of the 15 patients whose jejunal biopsy was studied after the eventual gluten challenge the jejunal lesion had returned in 2.4 to 28 months. The numbers of IgA- and IgM-containing cells were similarly raised in primary and postchallenge biopsies. In the 13 patients whose skin improved during a gluten free diet and who were challenged with gluten the rash worsened and the dapsone/sulphapyridine requirement increased. The jejunal deterioration was equally marked in the six patients whose gluten challenge was stopped because of an intractable rash as it was in those who completed the preplanned challenge. The specimens of the former, however, had significantly more IgA-containing cells than specimens of the latter. The number of intraepithelial lymphocytes clearly reflected the degree of intestinal damage. IgA-containing cells proved to be the most sensitive indicator of an immune reaction taking place in the gut of these patients. Even in the two children with initially normal or nearly normal jejunal mucosa, the IgA cell counts in the jejunal lamina propria were markedly raised.

HLA Antigens, Jejunal Morphology and Associated Diseases in Children with Dermatitis Herpetiformis

ABSTRACT. Forty‐five Hungarian and Finnish children from 1.5 to 15 years with dermatitis herpetiformis were studied for HLA antigens, jejunal morphology on gluten‐containing diet and associated diseases in the patients and their relatives. A strong association with HLA‐B8 was found in patients of both nationalities, the relative risks were 12.8 and 9.6, respectively. The Hungarian patients were also typed for HLA‐DR locus, and an association with DR3 but not with DR7 was observed. Patients with subtotal villous atrophy had slightly more often HLA‐B8 and DR3 than those with milder intestinal lesions. Atopic eczema occurred in 20 % of the patients and family history of atopy seemed to have an inverse correlation with HLA‐B8 and DR3.

Antiphospholipid antibodies in children

Sera from children (n= 173) were tested for antiphospholipid antibodies (aPL) using an enzyme immunoassay detecting IgG anti‐cardiolipin antibodies (GPL). Sera from adults (n= 100) were also tested. GPL were detected more frequently and at higher levels in children than in adults. Eighty‐two percent of the children and 27% of the adults tested positive (≥ 10 GPL Uml‐1) for aPL (p <0.001). Values of 45 GPLUml‐1 or higher were detected in about 5% of the children, and 25 GPLUml‐1 or higher in about 5% of the adults. Normal values should be adjusted accordingly.

HLA ANTIGENS IN INTESTINAL COW'S MILK ALLERGY

ABSTRACT. The histocompatibility antigens of one hundred patients with a severe form of cows milk allergy were studied. HLA‐A and B locus antigens were identified in all patients, C locus antigens in 62 patients and DR locus antigens in 41 patients. The A, B and C locus antigen frequencies were compared with those of healthy blood donors, and DR locus antigen frequencies with those of healthy unrelated volunteers and cadaver kidney donors. The series included six patients with concomitant coeliac disease, who were treated as a separate group. No statistically significant differences between the patients and controls were observed, but suggestive differences became apparent when the patient group was divided into subgroups according to the presence or absence of certain co‐existing conditions, and the severity of the initially observed intestinal lesion. It is concluded that several factors contribute to the pathogenesis of intestinal cows milk allergy, and that in some cases genes linked to the HLA region may play a role.