Autoantibodies to an epidermal protease inhibitor in skin diseases

Solid phase radioimmunoassay for measurement of autoantibodies in human sera to an epidermal protein is presented. The protein purified from normal human epidermis is inhibitory to SH-dependent proteases and its molecular weight is about 13,000. Antibodies were detected in 139 of the 4,400 sera collected from dermatological patients. Most of the patients suffered from wide-spread eczematous conditions. It is suggested that the antibodies are secondary to the inflammatory conditions, but they may exacerbate or delay the course of the disease.     

Autoradiographic visualization of glycoproteins and glycosaminoglycans in the epithelio-mesenchymal interface of developing mouse tooth germ

Abstract – The turnover of basement membrane macromolecules during tooth morphogenesis and odontobiast differentiation was examined by light microscopic autoradiography using ³H-fucose. ³⁵S-sulfate and ³H-glucosamine. Marked incorporation into the basement membrane was found throughout the progressive development. Pulse-chase experiments and prelabeling of tissue components indicated that glycoproteins and glycosaminoglycans in the dental basement membrane are mainly derived from the enamel epithelium. During odontobiast differentiation, incorporation was increased at the epithelio-mesenchymal interface at the site of differentiating mesenchymal cells. From these sites the label also disappeared rapidly. This suggests that the active remodeling of extracellular matrix is related to odontobiast differentiation.     

Rheumatoid factor in sera of dermatitis herpetiformis patients

Serum specimens from 44 patients with dermatitis herpetiformis (DH) and 42 control patients were analyzed with solid-phase radioimmunoassay (RIA) developed to detect IgG and IgM class antibodies against herpes simplex virus (HSV) envelope antigen. They were also tested with different tests to detect rheumatoid factor (RF) as well as serum antibodies to gastric parietal cells, glomerular basement membrane, smooth muscle, mitochondria and nuclei. Total serum IgG, IgM and IgA quantification was performed concurrently. IgM class antibodies reacting in HSV envelope antigen RIA were found in 47.8% of the DH patients, but in none of the controls. The age distribution of the IgM positive patients was in accordance with the appearance of RF, representing elderly persons. The presence of RF in serum specimens was confirmed by removing the IgM reactivity with heat aggregated human gamma globulin adsorption and in 13 patients with positive serological tests for RF. No correlation was found with the appearance of RF and duration or severity of the disease or with the detection of RF and serum total IgM concentration. In DH patients antibodies to gastric parietal cells were found in 6 and to smooth muscle in 1 of 32 specimens tested.     

The results of skin testing with food additives and the effect of an elimination diet in chronic and recurrent urticaria and recurrent angioedema

Ninety-one subjects suffering from chronic or recurrent urticaria or recurrent angioedema of 2 months to 17 yr duration were skin-prick and scratch tested with 18 various food additives. Twenty-four of the subjects (26%) had at least one histamine equivalent skin test (ST) reaction. In contrast, only 24 (10%) of 247 non-urticaria control subjects showed comparable results. An oral provocation test with food additives was carried out on 10 of the 24 ST-positive subjects with urticaria or angioedema, but only one positive reaction, caused by benzoic acid, was recorded. All 91 subjects were advised to follow an additive-free diet. The effect of the diet was investigated with a retrospective postal survey. Twenty-three ST-positive subjects returned the questionnaire, 18 had followed the diet, and 16 (89%) of these 18 had experienced marked relief of their symptoms. Correspondingly, 42 of the 47 ST-negative subjects had followed the diet, and 17 (40%) had improved. The difference was significant (P less than 0.05). Our results suggest that skin tests with food additives can be used to measure skin hyperreactivity and that they may have a predictive value in identifying patients who will respond to an additive-free diet.     

Mast cells and IgE in intestinal mucosa in adult atopic dermatitis patients

Duodenal biopsies from 29 adult atopic dermatitis (AD) patients with multiple positive skin prick test reactions were examined and the results compared with biopsies from 13 non-atopic controls. The duodenal mucosa showed mild inflammatory changes in six out of the 29 patients, but was normal in all the controls. Numerous anti-IgE positive cells, increasing with the severity of AD, were found in the duodenal mucosa in 25 of the 29 AD patients compared with few sporadic positive cells seen in only two out of 13 controls (P less than 0.001). The total serum IgE level showed a significant positive correlation with the number of anti-IgE stained cells in the mucosa (P less than 0.05). No significant differences were found in the total number of toluidine blue stained cells or cells immunoreactive for histamine between patients and controls. However, AD patients who had high numbers of anti-IgE positive cells often had decreased numbers of histamine immunoreactive cells in the mucosa suggesting mast cell degranulation. These findings provide further evidence that also in adult AD patients the gastrointestinal tract may serve as a portal of entry for allergens which may lead to exacerbation of AD.     

Candida albicans and atopic dermatitis

The role of sensitization and exposure to Candida albicans in atopic dermatitis (AD) was studied with skin-prick tests, yeast cultures and immunoblotting in 156 young adults with AD attending the Department of Dermatology, University of Turku, during 1983–89. Eighteen patients with allergic rhinitis without eczema and 39 non-atopics were included as controls. Parameters associated with severe AD were simultaneous anti-C. albicans IgE and saprophytic C. albicans growth. A statistically significant correlation between C. albicans sensitization (specific IgE antibodies) and AD symptoms was observed only in patients with saprophytic C. albicans exposure. No correlation between C. albicans-specific IgE and AD severity was shown in patients without gastrointestinal growth. Furthermore, severe eczema was seldom seen in patients without saprophytic C. albicans growth. The most important IgE-binding components of C. albicans in immunoblotting were 27 and 46 kD proteins and mannan, a polysaccharide. IgG and IgA antibodies to C. albicans, mainly towards C. albicans mannan, were found in practically all 70 sera studied. These results suggest a continuous exposure and induction of IgE antibodies by C. albicans in AD patients. Severe phases of AD in colonized patients are associated with IgE synthesis against C. albicans. These findings suggest a role for C. albicans in the exacerbations of AD but the clarification of this subject needs double-blind placebo-controlled treatment trials.     

Wheat grain immunofluorescent antibodies as an indication of gluten sensitivity?

An immunofluorescence method using whole sections of wheat grains as the substrate was applied to detect circulating antibodies to wheat gluten in dermatitis herpetiformis patients and in controls. Only IgG class antibodies were detected. From dermatitis herpetiformis patients 22% had these antibodies as had 22% of the atopic dermatitis group. Among the controls who had no skin problems 12% were faintly positive. It is evident that the test as such is non-specific and does not have diagnostic significance in dermatitis herpetiformis.     

Skin-prick test and RAST responses to cereals in children with atopic dermatitis. Characterization of IgE-binding components in wheat and oats by an immunoblotting method

Background Hypersensitiviiy to cereals may occur via inhalation or ingestion. Although cereals are essential in the daily nutrition, only little information is available of the allergens causing symptoms in patients with atopic dermatitis (AD). Objective The purpose of the present study was to analyse the IgE immune-response to various cereals and specific cereal fractions of wheat and oats in children with severe AD and correlate the results with challenge studies. Methods Skin-Prick tests (SPT) with a NaCL suspension of wheat. oats, rice, corn. millet and buckwheat and the ethenol soluble sliadin fraction of wheat were performed to 34 wheat/oats challange positive or negative children with AD Simultaneously serum total IgE and specific IgE antibody radioallergosorbent test (RAST), levels to wheat, oats and gluten were determined, In addition serum samples of these 34 AD patients and five age matched controls were analysed with IgE immunoblotting using neutral and acidic protien extracts of wheat and oats. Results From the 34 AD children 33 were SPT positive with wheat and 18 with oats. Positive RAST to wheat and oats could be detected in 32 and 30 samples respectively. From the oral Wheat challange positive children 12/14 appeared positive with gliadin SPT and revealed positive RAST to gluten, but each of the wheat challenge negative were negtive in SPT with gliadin. In immunoblotting using neutral and acidic fractions of cereals the IgE binding with sera of challenge positive children showed the most intensive staining, but no correlation was found between differrent staining patterns and the clinical wheat sensitivity. The 26,38 and 69 KDa bands in wheat and the 46 and 66 KDa in oats could be classified as major IgE binding proteins of these cereals (>50% of the sera were positive). SPT with rice, corn, miller or buckwheat and oats was positive in 16/34 patients. Conclusion Intensive IgE staining to natural acidic soluble proteins in wheat and oats was seen with major IgE binding to 26.38 and 69 KDa protiens in wheat and 46 and 66 KDa in oats, but no specific IgE staining patterns correlating with clinical cereal sensitivity were found. The strong association between the positive SPT with the ethnol soluble gliadin suggest that also gliadin is an important allergen in wheat-allergic children with AD. The allergens in rice, corn, millet and buckwheat should be better studied before they can be recommended as alternatives for cereal allergic children.