Timo Reunala

Coeliac disease--associated disorders and survival.

The associated diseases in 335 coeliac patients diagnosed 1980-90 were compared with age and sex matched control patients with various gastrointestinal symptoms. Endocrine disorders were found in 11.9% of coeliac and 4.3% of control patients (p = 0.0003). Coeliac patients had insulin dependent diabetes mellitus significantly (p = 0.0094) more often (5.4%) than control patients (1.5%). connective tissue diseases were found in 7.2% of coeliac and in 2.7% of control patients (p = 0.011). Sjögrens syndrome occurred in 3.3% of coeliac patients and in 0.3% of controls (p = 0.0059). Autoimmune thyroid diseases were found in 5.4% and asthma in 3.6% of coeliac patients, but also in 2.7% and 3.6%, respectively, among control patients. The incidences of malignant diseases and the survival rate in coeliac patients were compared with those in the Finnish population. Ten coeliac patients developed a cancer during the follow up (mean 5.3 years, range 1-12) but none had a lymphoma. The risk of malignant diseases in coeliac patients did not differ from that in the Finnish population in general. Eleven coeliac patients died during the follow up. The five year survival rates of coeliac patients did not differ from those in the general population. At least 83% of the coeliac patients adhered strictly to the gluten free diet, which may explain the favourable outcome.

A novel wheat gliadin as a cause of exercise-induced anaphylaxis.

BACKGROUND Food-dependent, exercise-induced anaphylaxis is a severe form of allergy; the reaction is caused by ingestion of a specific food before exercise. This disorder often escapes diagnosis because neither the ingested food nor the exercise alone induces the symptoms. OBJECTIVE The aim of the study was to characterize the allergens involved in wheat-dependent, exercise-induced anaphylaxis and to describe the clinical outcome in a series of 18 adult patients. METHODS All 18 patients had experienced recurrent episodes of generalized urticaria during exercise, 17 patients in association with collapse and 15 patients with an anaphylactic reaction. The symptoms appeared only when the patients had eaten food containing wheat before exercise. Wheat allergens were detected by immunoblotting, purified by gel filtration and reversed-phase chromatography, and subjected to N-terminal sequencing. The IgE-binding ability of the purified proteins was studied by ELISA, and their in vivo reactivity was studied by skin prick testing. RESULTS IgE antibodies from pooled patient sera were bound to 65-kd and 40-kd wheat proteins in immunoblotting. The 65-kd allergen was a previously undescribed wheat protein, showing 61% sequence identity to gamma-gliadin, whereas the 40-kd allergen had 100% identity to alpha-gliadin. In ELISA, all 18 patients showed elevated IgE levels to the novel gamma-like gliadin, and 13 of the patients showed elevated IgE levels to the alpha-gliadin. None of the 54 control subjects with wheat allergy, urticaria, or coeliac disease had IgE antibodies to the gamma-like gliadin. The in vivo reactivity of the gamma-like gliadin was verified by positive skin prick test responses in all of the 15 patients who were tested. During the follow-up on a gluten-free or wheat-free diet, 3 patients experienced reactions after having unknowingly eaten wheat before exercise, but all the other patients who were adhering to the diet remained symptom-free. CONCLUSION This study shows that wheat is a frequent cause of food-dependent, exercise-induced anaphylaxis and suggests that the major allergen is a previously undescribed gamma-like gliadin. For screening of this life-threatening allergy, we recommend skin prick testing with crude gliadin and we recommend a gluten-free diet for treatment.

Selective IgA Deficiency and Coeliac Disease

Twenty-five children and adults with concomitant coeliac disease and selective IgA deficiency are described. IgG-class reticulin antibodies were positive in 94%. The clinical course of coeliac disease did not differ from that of patients with normal serum IgA level. Patients with IgA deficiency also had other concomitant diseases, especially autoimmune diseases. Patients with selective IgA deficiency have at least a tenfold risk of coeliac disease compared with the population in general.

Comparison of diagnostic methods in latex surgical glove contact urticaria

Surgical rubber gloves contain allergens derived from natural rubber latex which may sensitize, causing contact urticaria and even systemic reactions. We examined 15 hospital employees allergic in latex surgical gloves, using various skin tests and RAST, to determine the most reliable diagnostic method and to investigate coexistent allergy to glove powder and rubber chemicals. Prick testing using a stock solution made from one brand of latex glove yielded positive (2+ to 4+) reactions in all 15 employees; 8 retained positive reactions at a 1/10 dilution, 1 at 1/100 and 4 at 1/1000. A prick test using rubber‐tree sap (Hevea brasiliensis) was positive in 12/15 employees and a scratch‐chamber test using crushed rubber‐tree leaf was positive in 13/l5. A latex glove use test was positive in 12/13 employees and a latex RAST detected measurable amounts of specific IgE in 8/15. No positive prick lest reactions were obtained using glove powder. On patch testing, 2/15 employees showed delayed allergy to rubber chemicals but no immediate reactions were detected, The present results indicate that in addition to the use test, prick testing with a stock solution prepared from latex surgical gloves is an adequate test method for routine practice when diagnosing latex glove contact urticaria The correlation between prick tests and whole glove me tests was good, but latex RASTs yielded some negative results.

IgA ANTIGLIADIN ANTIBODIES: A MARKER OF MUCOSAL DAMAGE IN CHILDHOOD COELIAC DISEASE

Antigliadin antibodies in serum samples of 31 children with coeliac disease were measured by an enzyme-linked immunosorbent technique. In young patients (less than 2 years) tested before gluten withdrawal IgA antigliadin antibody levels were invariably above the levels of 36 controls. The titres fell rapidly when gluten was eliminated from the diet and rose on its reintroduction. The titres were not always greater than the control level in older untreated patients. IgA antigliadin antibodies seem to be a good marker of the immune reaction in the jejunum triggered by gluten. In 2 IgA-deficient patients gluten challenge caused an increase in IgM antigliadin antibodies, and at the same time the number of IgM-containing cells increased in the jejunal mucosa. Rising IgG antigliadin antibody levels after gluten elimination were seen in 6 patients, 5 of whom had very low complement C3 levels before gluten elimination.

IL-33 and ST2 in atopic dermatitis: expression profiles and modulation by triggering factors.

In the acute phase of atopic dermatitis (AD), T-helper type 2 (Th2) cytokines characterize the inflammatory response in the skin. IL-33 is a new tissue-derived cytokine, which is mainly expressed by cells of barrier tissues, and is known to activate Th2 lymphocytes, mast cells, and eosinophils. IL-33 signals through a receptor complex consisting of IL-33-specific receptor ST2 and a co-receptor IL-1RAcP. As IL-33 is known to promote Th2-type immunity, we examined expression profiles of IL-33 and its receptor components in human AD skin, in the murine model of AD, and in various cell models. We found increased expression of IL-33 and ST2 in AD skin after allergen or staphylococcal enterotoxin B (SEB) exposure, as well as in the skin of 22-week-old filaggrin-deficient mice. In addition, skin fibroblasts, HaCaT keratinocytes, primary macrophages, and HUVEC endothelial cells efficiently produced IL-33 in response to the combined stimulation of tumor necrosis factor-α and IFN-γ, which was further enhanced by a mimetic of double-stranded RNA. Finally, the increased expression of IL-33 and ST2 caused by irritant, allergen, or SEB challenge was suppressed by topical tacrolimus treatment. These results suggest an important role for IL-33-ST2 interaction in AD and highlight the fact that bacterial and viral infections may increase the production of IL-33.

Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits

Background: Some patients with untreated coeliac disease are negative for serum endomysial autoantibodies (EmA) targeted against transglutaminase 2 (TG2). Aims: To evaluate the clinical and histological features of EmA-negative coeliac disease, and to examine whether EmA-equivalent autoantibodies against TG2 can be seen in the small-bowel mucosa when absent in serum. Patients: Serum EmA was studied in 177 biopsy-proved specimens from adult patients with coeliac disease. 20 patients with intestinal diseases served as non-coeliac controls; three had autoimmune enteropathy with villous atrophy. Methods: Clinical manifestations, small-bowel mucosal morphology, intraepithelial inflammation and TG2-specific extracellular immunoglobulin A (IgA) deposits were investigated in both serum EmA-negative and EmA-positive patients. Results: 22 patients with IgA-competent coeliac disease were negative for serum EmA. Three of these had small-bowel lymphoma. Patients with EmA-negative coeliac disease were older, had abdominal symptoms more often, and the density of γδ+ intraepithelial lymphocytes in their intestinal mucosa was lower than in EmA-positive patients; otherwise the histology was similar. All serum EmA-negative patients with coeliac disease, but none of the disease controls, had gluten-dependent mucosal IgA deposits alongside TG2 in the small-bowel mucosal specimens. In vivo deposited IgA was shown to be TG2-specific by its ability to bind recombinant TG2. Conclusions: Negative serum EmA might be associated with advanced coeliac disease. TG2-targeted autoantibodies were deposited in the small-bowel mucosa even when absent in serum. This finding can be used in the diagnosis of seronegative coeliac disease when the histology is equivocal. It may also be helpful in the differential diagnosis between autoimmune enteropathy and coeliac disease.

Rubber contact urticaria. Allergenic properties of 19 brands of latex gloves

To compare the immediate skin test reactivity of various latex (natural rubber) surgical and cleaning gloves. prick tests were performed on 40 latex‐allergic persons, 26 of whom were sensitized by surgical and 14 by cleaning latex gloves. 6/17 surgical gloves tested and 1/2 cleaning gloves caused positive reactions in almost all (over 87%) of the allergic subjects. In contrast. the frequencies of positive reactions to 4 other surgical latex gloves were us low as 8–21%, suggesting that not all surgical gloves arc equally allergenic. Control prick tests with I synthetic rubber and 1 polyvinyl chloride (PVC) glove were negative in all subjects. 2 surgical latex gloves causing either a high or low number of positive prick tests in allergic subjects were analyzed with high‐pressure liquid chromatography (HPLC). Similar allergenic protein fractions were detected, which showed protein peaks at MW 2000 5000 and 3000 daltons. Corresponding proteins were detected in I latex cleaning glove analyzed and in natural rubber. This result confirms that allergnic proteins persist in various surgical and cleaning latex gloves after manufacture from natural rubber and may cause contact, urticaria symptoms toms in sensitized people.

Smoking, alcohol and life events related to psoriasis among women

Possible risk factors for psoriasis were studied among women aged 18–50 years. The series consisted of 55 consecutive psoriatic patients and 108 unmatched controls with other skin diseases, from the university departments of dermatology in Helsinki, Oulu and Tampere. A questionnaire focused on two specified periods of time, 12 months before the onset of the skin disease and 12 months before the examination date. Before the onset of the skin disease, the recalled mean number of cigarettes smoked daily was 8.6 (1.2 SE) for psoriatics and 4.7 (0.7) for controls (P=0.004). The respective alcohol intake figures (mean±SE) were 8.0 (2.2) and 4.7 (0.8) g/day (P= 0.17). In logistic regression analysis, psoriasis was associated significantly with smoking, but not with alcohol intake, marital status or social group. The odds ratio for psoriasis for those smoking 20 cigarettes daily compared with non‐smokers was 3.3 (95% confidence limits 1.4‐7.9). The odds ratio for psoriasis at an alcohol intake of 20 g/day compared with no intake was 1.8 (1.0–3.3). After the onset of the disease, psoriasis was associated significantly with alcohol intake, smoking, and the occurrence of negative life events. Among psoriatics, skin surface involvement was significantly associated with alcohol intake (P= 0.04), but not with smoking or negative life events. These results suggest that smoking is a risk factor for psoriasis in women, and that alcohol intake worsens their psoriasis. Smoking and negative life events were more common among psoriasis patients than among controls, perhaps as consequences of the disease.

Immunoglobulin A autoantibodies against transglutaminase 2 in the small intestinal mucosa predict forthcoming coeliac disease

Reliable markers of early developing coeliac diseases are needed. Coeliac autoantibodies in the serum or Marsh I inflammation may be indicators of subsequent coeliac disease.