Type Skin Reactions Research Articles

Calcium-dependent immunoglobulin E recognition of the apo- and calcium-bound form of a cross-reactive two EF-hand timothy grass pollen allergen, Phl p 7.

Type I allergy, an immunodisorder that affects almost 20% of the population worldwide, is based on the immunoglobulin E (IgE) recognition of per se innocuous antigens (allergens). Pollen from wind-pollinated plants belong to the most potent allergen sources. We report the isolation of a cDNA coding for a 8.6 kDa two EF-hand calcium binding allergen, Phl p 7, from a timothy grass (Phleum pratense) pollen expression cDNA library, using serum IgE from a grass pollen allergic patient. Sequence analysis identified Phl p 7 as a member of a recently discovered subfamily of pollen-specific calcium binding proteins. Recombinant Phl p 7 was expressed in Escherichia coli and purified to homogeneity as determined by mass spectroscopy. Approximately 10% of pollen allergic patients displayed IgE reactivity to rPhl p 7 and Phl p 7-homologous allergens present in pollens of monocotyledonic and dicotyledonic plants. Circular dichroism analysis of the calcium-bound and apo-rPhl p 7 indicated that differences in IgE recognition may be due to calcium-induced changes in the protein conformation. The fact that patients mount IgE antibodies against different protein conformations is interpreted as a footprint of a preferential sensitization against either form. The biological activity of rPhl p 7 was demonstrated by its ability to induce basophil histamine release and immediate type skin reactions in sensitized individuals. In conclusion, IgE binding to Phl p 7 represents an example for the conformation-dependent IgE recognition of an allergen. Recombinant Phl p 7 may be used for diagnosis and perhaps treatment of a group of patients who suffer from allergy to pollens of many unrelated plant species.

Expression of a Human IgG4 Antibody, BAB2, with Specificity for the Major Birch Pollen Allergen, Bet v 1 in Escherichia coli: Recombinant BAB2 Fabs Enhance the Allergic Reaction

Background: Antigen recognition by antibodies of different isotypes can result in completely different effects as exemplified by Type I allergy. While the IgE–antibody–mediated release of biological mediators constitutes the immunopathological basis for the immediate symptoms observed in allergic patients, allergen–specific IgG antibodies are thought to have protective effects. Methods: Cell lines secreting five human monoclonal IgG antibodies (BAB1–BAB5) with specificity for the major birch pollen allergen Bet v 1 were established from a birch–pollen–allergic patient who had received birch– pollen–specific immunotherapy. The influence of the Bet v 1–specific IgG antibodies on IgE binding to Bet v 1 was investigated. BAB2 was expressed in Escherichia coli as recombinant Fab, purified and tested for its ability to modulate Bet v 1–induced immediate–type skin reactions. Results: The BAB antibodies belonged to different IgG subclasses (BAB1: IgG1; BAB2, BAB3, BAB5: IgG4; and BAB4: IgG2) reflecting a tendency towards Th2. BAB1 represented the only antibody which strongly blocked IgE binding to Bet v 1, whereas BAB 3–BAB5 had little effect on IgE binding. Surprisingly, natural BAB2 antibodies as well as recombinant BAB2 Fabs strongly enhanced IgE binding to Bet v 1 and Bet v 1–induced immediate–type skin reactions and thus represent ‘enhancing antibodies’. Conclusion: The demonstration that anti–allergen IgG antibodies can also enhance IgE binding to a given allergen explains the unpredictability of specific immunotherapy as well as the controversy on the role of IgG in atopy.

Molecular and Immunologic Characterization of a Highly Cross-Reactive Two EF-Hand Calcium-Binding Alder Pollen Allergen, Aln g 4: Structural Basis for Calcium-Modulated IgE Recognition

Serum IgE was used to isolate a cDNA coding for a 9.4-kDa two EF-hand calcium-binding allergen, Aln g 4, from a lambda gt11 expression cDNA library constructed from alder (Alnus glutinosa) pollen. rAln g 4 was overexpressed in Escherichia coli and purified to homogeneity. It reacted with serum IgE from 18% of pollen-allergic patients (n = 122); shared IgE epitopes with homologous allergens present in tree, grass, and weed pollens; and thus belongs to a family of highly cross-reactive pollen allergens. Exposure of two E. coli-expressed rAln g 4 fragments comprising amino acids 1-41 and 42-85 to patients' IgE Abs, as well as to a rabbit antiserum raised against purified rAln g 4, indicated that most of the B cell epitopes reside in the N-terminal portion of the protein. IgE recognition of Aln g 4 was strongly modulated by the presence or absence of calcium. Circular dichroism analysis of rAln g 4 revealed that the protein consisted mostly of alpha helical secondary structure and possessed a remarkable thermal stability and refolding capacity, a property that was greatly reduced after calcium depletion. Circular dichroism analysis of the calcium-bound and apo form of rAln g 4 indicated that calcium-induced modulation of IgE binding could be due to changes in the protein conformation. Purified rAln g 4 elicited dose-dependent basophil histamine release and immediate type skin reactions in sensitized patients. It may hence be useful for allergy diagnosis and for specific immunotherapy.

Isolation of cDNA clones coding for IgE autoantigens with serum IgE from atopic dermatitis patients.

Recently we demonstrated that a high percentage of atopic dermatitis (AD) patients displayed specific immunoglobulin E reactivity to human proteins. Here we show that IgE autoreactivity is found predominantly in AD patients with severe skin manifestations and reveal the molecular nature of four IgE autoantigens. An expression cDNA library constructed from a human epithelial cell line (A 431) was screened with serum IgE from two AD patients. DNA sequence analysis of three IgE-reactive clones identified the alpha-chain of the nascent polypeptide-associated complex, cytokeratin type II, and the BCL7B oncogen as atopy-related IgE autoantigens (ara). The fourth cDNA coded for an IgE autoantigen containing a typical calcium binding motif that occurred in histogenetically different cells and tissues (keratinocytes, muscle, brain). Recombinant Escherichia coli-expressed IgE autoantigens bound IgE from AD but not from patients with other immunologically mediated disorders (graft vs. host disease, systemic lupus erythematosus) and elicited immediate type skin reactions in AD patients. In serum samples collected from an AD patient over a period of 5 years, IgE anti-ara NAC antibody levels peaked during disease exacerbation. Our finding that ara BCL7B was detected in serum bound to IgE antibodies suggests that intracellular IgE autoantigens can become released after tissue damage and may occur as IgE immune complexes. Via binding to antigen presenting cells as well as to effector cells, IgE autoantigen immune complexes may contribute to exacerbation and/or perpetuation of severe atopic diseases even in the absence of exogenous allergens.

An assessment of antigenic potential of β-lactam antibiotics, low molecular weight drugs, using guinea pig models

Allergic reactions are among the common adverse effects in humans. However, it is widely assumed that there are practically no reliable animal models for preclinical tests of low-molecular weight drugs that are available to predict such reactions. This study was designed to compare the detecting ability of test methods for antigenic potential of eight β-lactam antibiotics with which allergic outcome has been reported in humans. The tests included active systemic anaphylaxis (ASA), delayed type skin reaction (DSR), maximization test (GPMT) in guinea pigs sensitized with antibiotics emulsified with Freund's complete adjuvant, passive cutaneous anaphylaxis (PCA) and enzyme-linked immunosorbent assay (ELISA) as serological tests. PCA and ELISA though using protein-conjugates as detecting antigens, especially ELISA, showed positive reactions with relatively high incidence. On the other hand, GPMT was the most sensitive method to detect antigenic potential of antibiotics despite the use of antibiotics alone for sensitizing and challenging phases. It is suggested that GPMT can be considered the most reliable method in preclinical testing.

Adhesion molecules in atopic dermatitis: patch tests elicited by house dust mite.

Different T-helper subsets, which are characterized by the secretion of distinct cytokines (Th1, Th2), have been found in house dust mite-exposed skin of sensitized individuals and in nickel-specific T lymphocytes from nickel contact allergic and non-allergic individuals. In order to evaluate the role which adhesion molecules may play in the homing of different T-cell subsets into allergen-exposed skin of atopic and normal individuals, we compared the expression pattern of adhesion molecules in patch test reactions to house dust mite antigen (D.pt.), nickel sulfate (Ni) and the irritant anthralin. Biopsies were taken at various time points after application of these agents and studied by immuncytochemistry. To exclude an endogenous difference in adhesion molecule expression in atopic and non-atopic skin, sequential biopsies from Ni patch tests of 2 normal individuals were also included in this study. The expression of E-selectin, P-selectin, CD31, VCAM-1 and ICAM-1 on endothelial cells and other cells in the skin was quantified by microscopic evaluation. Skin homing T cells were also quantified using antibodies to CD3, CD4, CD8, UCHL-1, L-selectin and the cutaneous lymphocyte antigen (CLA). Independent of the eliciting substance, all lesions showed an upregulation of all adhesion molecules tested, with the exception of CD62. The appearance of E-selectin and an increase in ICAM-1 and VCAM-1 expression were first observed at 12 h after application of the various agents. In parallel, the number of CLA+ and L-selectin+ lymphocytes increased steadily. No principle differences could be established between the various types of skin reactions in atopic individuals, nor did the skin of patients with AD differ from normal controls. Our results provide evidence that differential expression of adhesion molecules does not play a major part in observed differential homing of Th1 and Th2-cell subsets into patch test sites provoked by house dust mite and nickel sulfate in atopic and non-atopic individuals.

S231 Type of skin reaction to carbamazepine is determined by type of immunologic response

S231 Type of skin reaction to carbamazepine is determined by type of immunologic response

High-Level Expression inEscherichia coliand Purification of Recombinant Plant Profilins: Comparison of IgE-Binding Capacity and Allergenic Activity

Because of their structural similarity and ubiquituous distribution as actin binding proteins, plant profilins represent important cross-reactive allergens for almost 20% of patients suffering from Type I allergy to pollen and other plant products. The cDNAs coding for three birch profilin variants (Tyr44, Glu47, and Asn47), timothy grass profilin, and three tobacco profilin isoforms (ntprof1-3) were expressed at high levels inEscherichia colias non-fusion proteins. The recombinant plant profilins were purified to homogeneity by poly (L-proline) affinity chromatography and showed comparable capacity to bind IgE-antibodies from profilin allergic patients. All recombinant plant profilins elicited dose-dependent histamine release from basophils of a profilin allergic patient and induced immediate type skin reactions. It is concluded that profilins from different plant species share IgE-epitopes and allergenic properties. Plant profilins therefore constitute a family of functional pan-allergens which may substitute each other for diagnosis and specific immunotherapy.

Results of a randomized comparison of radiotherapy and bromodeoxyuridine with radiotherapy alone for brain metastases: Report of RTOG trial 89-05

Purpose : To determine if the addition of bromodeoxyuridine (BrdUrd) to radiotherapy prolongs survival when compared to radiotherapy alone in patients with brain metastases. Methods and Materials : Seventy-two patients with brain metastases were randomized to 37.5 Gy in 15 fractions of 2.5 Gy or to the same dose with BrdUrd 0.8 g/m 2 per day for 4 days of each of 3 weeks. Drug treatment was begun on Thursday or Friday before the first week of radiotherapy. Patients had a Karnofsky performance score of at least 70, a neurological function classfication of 1 or 2, and any primary tumor except central nervous system (CNS), leukemia, or lymphoma. The primary was absent, controlled, or under active radiotherapy. Patients were free of other metastases. They were stratified by primary site (breast, lung or other), number of metastases (single or multiple) and age (< 60 vs. > 60). Results : There was no significant difference between the two treatment arms ( p = 0.904). The study was open from October 1989 to March 1993 and accrued 72 patients. Only one patient in the RT only arm remains alive. The two treatment arms were balanced with respect to all stratification variables. Toxicity due to radiotherapy was similar in both arms. BrdUrd caused significant Grade 4 and 5 hematologic and skin toxicity in five patients. Two patients died due to hematologic toxicity and one from a Stevens-Johnson type skin reaction. Phenytoin played a role in the skin reactions and ranitidine was associated with the hematologic deaths. Ranitidine was eliminated, BrdUrd was discontinued after any hematologic toxicity, and no further Grade 4 or 5 toxicities were seen. The median survival was 6.12 months in the radiotherapy group and 4.3 in the BrdUrd group ( p = 0.904). Patients with solitary brain metastases had significantly better survival ( p = 0.031). Conclusions : BrdUrd did not enhance the efficacy of the radiotherapy regimen tested, in spite of the fact that brain metastases have shown high labeling indices. The toxicity of this schedule of BrdUrd administration was apparently increased by ranitidine and phenytoin.

Computed tomographic scanning of the lung in patients with allergic bronchopulmonary aspergillosis and in asthmatic patients with a positive skin test to Aspergillus fumigatus.

Allergic bronchopulmonary aspergillosis is a disease of asthmatic patients which may follow a protracted course and result in chronic lung damage such as central bronchiectasis. In asthma uncomplicated by allergic bronchopulmonary aspergillosis, in particular in asthmatic patients with immediate hypersensitivity type skin reactions to Aspergillus fumigatus, the incidence of bronchiectasis is uncertain. Computed tomographic (CT) scans were performed in 17 asthmatic patients of mean (SE) age 60.1 (2.5) years, FEV1 49.4 (5.8)% predicted with allergic bronchopulmonary aspergillosis (all with current or previous positive precipitins to A fumigatus) and in 11 asthmatic patients of mean (SE) age 49.5 (5.8) years, FEV1 75.5 (6.5)% predicted, skin test positive for A fumigatus, but without the clinical or serological features of allergic bronchopulmonary aspergillosis (non-allergic bronchopulmonary aspergillosis group). Bronchial dilatation was more common in the group with allergic bronchopulmonary aspergillosis, affecting 14 patients compared with two in the non-allergic bronchopulmonary aspergillosis group. Evidence of bronchiectasis was found in 43 of a possible 102 lobes of patients with allergic bronchopulmonary aspergillosis, compared with three of a possible 66 in the non-allergic bronchopulmonary aspergillosis group. Bronchial wall thickening was common to both, affecting 16 and nine patients respectively. Pleural thickening on CT scanning was common in the group with allergic bronchopulmonary aspergillosis, being noted in 14 patients compared with only three in the non-allergic bronchopulmonary aspergillosis group. Bronchiectasis is common in allergic bronchopulmonary aspergillosis but occurs only occasionally in asthmatic patients with a positive skin test to A fumigatus but without other features of the disease.

Generalized autosensitization to a localized eczematoid dermatitis induced by ionizing radiation

Autosensitization was originally defined by Whitfield as form of autointoxication derived from changes in patient's own tissues. He reported three patients in whom a generalized skin eruption developed after a localized nonpenetrating cutaneous injury or a localized inflammatory dermatitis.' Subsequently has been reported in patients with dermatophyte infection, scabies, localized burn, localized bacterial infection.I stasis dermatitis.' and many other types of dermatitis. Later a more contemporary definition for was proposed by Rook, who stated that autosensitization is sensitization of body by circulating antibody, or a delayed cellular-type antibody, or both, to constituents of its own tissues. The most recognized form of dermatitis is autoeczematization, defined as the process by which a widespread dermatitis may complicate several types of localized eczema.? Radiotherapy causes several types of acute skin reaction/' The most common is primary reaction at treatment site that usually consists of dry or moist erythema, desquamation, or both.' At high dosages of radiation, blisters, erosions, or ulcerations may occur. Another type of skin reaction is a localized eczematoid dermatitis that is either confined to treatment sites or contiguous areas. A rare reaction is a generalized erythema multiforme-like eruption in patients who received deep radiothera-

Differential Cytokine Profiles in Peripheral Blood Lymphocyte Supernatants and Skin Biopsies from Patients with Different Forms of Atopic Dermatitis, Psoriasis and Normal Individuals

There is increasing evidence that the activation of a selected T helper cell population producing a Th2-related cytokine pattern with IL-4 and IL-5 but not IL-2 and interferon-gamma (IFN-gamma) may be involved in the pathogenesis of IgE-mediated atopic diseases and in particular of atopic dermatitis (AD). However, the existence of a 'nonatopic' (intrinsic) form of AD (NAD) with normal serum IgE levels, negative RAST tests, negative immediate type skin reactions towards environmental allergens and a negative patients and family history for IgE-mediated allergies raised the question whether this form may be explained by a different T cell activation and cytokine pattern. In the present study we compared the distribution of peripheral blood leukocyte and lymphocyte subpopulations, their activation state and cytokine production in peripheral blood lymphocyte supernatants and skin biopsies of patients with AD (n = 19), NAD (n = 14), psoriasis (n = 6) and normal individuals (n = 13). A characteristic eosinophilia was present in AD and NAD but not in psoriasis and normal controls. The three patient groups showed significantly increased numbers of activated CD4+ and CD8+ cells as measured by IL-2R and HLA-DR expression. Determination of spontaneously released IL-2, IL-4, IL-5 and IFN-gamma from peripheral blood lymphocytes demonstrated a Th2-related cytokine pattern with elevated levels for IL-4 and IL-5 in AD patients only. Increasingly enough, patients with NAD displayed high IL-5 but low IL-4 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigenicity study of trandolapril (RU44570)

Antigenicity of trandolapril (RU44570) was evaluated using the following six standpoints: 1. active systemic anaphylaxis (ASA) in guinea pigs; 2. passive cutaneous anaphylaxis (PCA) in guinea pigs with serum of sensitized guinea pigs; 3. histamine release from lung tissue of sensitized guinea pigs; 4. Schultz-Dale reaction with isolated ileum of sensitized guinea pigs; 5. passive cutaneous anaphylaxis (PCA) in rats with serum of sensitized mice; and 6. delayed type skin reaction by Maximization test in guinea pigs. In the test of immediate type reactions, guinea pigs were sensitized by RU44570 (p.o.), an FCA emulsion of RU44570 (s.c.) or an FCA emulsion of incubate solution of RU44570 and normal guinea pig's serum, and mice were sensitized by a mixture of RU44570 and alum (i.p.). In the test of delayed type reaction, guinea pigs were sensitized by intradermal injection and patch application. 1. ASA in guinea pigs: No anaphylaxis symptoms were observed in any of the sensitized guinea pigs. 2. PCA in guinea pigs: PCA titer of sera from all the sensitized animals was less than 1. 3. Histamine release from lung tissue: No histamine release was observed in any of the isolated lung tissue. 4. Schultz-Dale reaction: No contraction was observed in any of the isolated ileums. 5. PCA in rats: PCA titer of sera from sensitized BALB/c and C3H/He mice was less than 5. 6. Delayed type skin reaction test: No skin reactions were observed in any of the sensitized guinea pigs. From these results, it is concluded that RU44570 has no antigenicity under the conditions of the present study.

ヒドロキシアパタイトおよびβ‐リン酸三カルシウムの抗原性に関する実験的検討

The antigenicity of two products of hydroxyapatite (HAP), supplied by two Japanese manufacturers, and three products of tricalcium phosphate (β-TCP), supplied by two Japanese and one American manufacturers, was studied by means of delayed type skin reactions in guinea pigs.Skin reactions were elicited by injection of the ceramic into the dorsal skin 13 or 14 days after being immunized by intradermal injection of HAP or β-TCP into the dorsal flanks or footpads of guinea pigs.After 24 hours. skin reactions were assessed by measuring the diameter of erythema and the degree of hemorrhage and induration.The results were as follows:1. Antigenicity was not detected for the HAP obtained from Asahi Optical Co., Ltd. and LION Co., Ltd.(self setting α-TCP) by means of skin reactions.2. Antigenicity was not detected for the β-TCP obtained from Asahi Optical Co., Ltd. and Kyocera Co., Ltd.3. In contrast, β-TCP from MITER, INC, USA (Synthograft®) induced delayed type hypersensitivity (DTH) 24 hours after antigen elicitation. The reaction appeared to be based on tuberculin and Jones-Mote types of reactions.4. In the present study, Arthus reaction was not seen in any group of animals, indicating that HAP and β-TCP did not induce antibody formation.

Relationship between autoimmune diseases and pneumoconiosis

In recent years, with the aging of patients with pneumoconiosis, autoimmune diseases as a complication have been observed. One of the reasons for this may be that autoimmune diseases are prone to develop among the elderly. On the other hand, it has been reported that dust itself, such as silica for example, has adjuvant effect. A review of the recent literature published in Japan and abroad was made to clarify the relationship between pneumoconiosis and autoimmune diseases and the following results were obtained. 1) Disorders which accompany pneumoconiosis: Scleroderma, rheumatoid arthritis, systemic lupus erythematosus (SLE), and disorders of the kidney and liver have been reported. In Japan, about 30 cases of pneumoconiosis accompanied with autoimmune diseases have been reported. In many of the reports, patients with pneumoconiosis and scleroderma have a past history of exposure to silica. In both case studies and case control studies, patients with rheumatoid arthritis and history of silica exposure are prone to develop pneumoconiosis. 2) Immunological studies of patients with pneumoconiosis: As for humoral immunity, elevation of polyclonal gamma-globulin, especially IgG, has been often reported together with high positive rate of autoantibodies such as antinuclear antibodies. In cellular immunity, decreased delayed type skin reaction and decreased CD4/8 ratio have been reported. In human leukocyte antigen (HLA) typing the elevated frequency of DR4 has been reported. In the study of BAL increased production of superoxide anion O2- by alveolar macrophages has been observed. 3) EXPERIMENTAL STUDIES: Silica is well known for its toxicity to cells and also for its adjuvant effect. In the German Democratic Republic, patients with scleroderma and history of long term silica exposure are recognized as patients with occupational disease even though pneumoconiosis is not clearly demonstrated on X-ray film. It is difficult from this review to nrake a definite conclusion regarding the relation between silicosis and autoimmune diseases. There is a need to repeat this review of the literature on autoimmune diseases and pneumoconiosis in the near future.

Rhipicephalus appendiculatus: Immunochemical isolation, identification and characterization of tick gut antigens recognized by IgGs derived from rabbits repeatedly infested with ticks

Immune resistance to infestation by the brown ear tick, Rhipicephalus appendiculatus Neumann, was induced in rabbits by repeated tick feeding. Antibodies from the rabbits resistant to ticks were purified and used to isolate tick midgut antigens. Purified immunoglobulin G (IgGs) from rabbits immune to tick infestations demonstrated, by immunoblotting, nine protein subunits with molecular weights ranging from 12,000 to 92,000 daltons. Immuno-adsorption studies revealed an aggregated native protein with a molecular weight greater than 500,000 daltons as resolved by polyacrylamide gel electrophoresis (PAGE). Sodium dodecyl sulphate (SDS)-PAGE of this protein molecule revealed the presence of 14 protein subunits similar to some of those detected by the immunoblots. Their molecular weights ranged from 14,000 to 165,000 daltons. Sera from rabbits immunized with the 500,000 dalton molecule formed a weak precipitating arc in the immunodiffusion test, confirming its immunogenicity. The reproductive potential of ticks fed on rabbits immunized with the purified protein molecule was slightly affected compared to controls. The protein molecule also had the capacity to induce immediate and delayed type skin reactions when injected into rabbits resistant to adult R. appendiculatus , as opposed to control tick-naive rabbits.

Application of leucocyte migration tests to detection of allergenic drugs in patients with hypersensitivity to β-lactam antibiotics

In 90 suspected cases of beta-lactam hypersensitivity manifesting exanthema, pyrexia and hepatopathic symptoms, the identities of the allergenic drugs were investigated by immediate type skin reactions, sensitized erythrocyte agglutination tests and leucocyte migration inhibition tests (LMIT). In addition 30 control patients were tested for hypersensitivity to ampicillin, cephalexin and latamoxef. The control patients manifested the same symptoms as the patients with suspected hypersensitivity to beta-lactam but had not been treated with beta-lactam antibiotics. In the immediate type skin reaction, all the control cases as well as all the suspected beta-lactam hypersensitive patients displayed negative reactions to each of the antibiotics tested. In the sensitized erythrocyte agglutination tests, no antibodies to any of the three drugs were detected in the control group, while antibodies with a titre of 1:2 or more were detected in only 7% (6/90) of the suspected beta-lactam hypersensitive patients. On the other hand, in the LMIT, only 4% (4/90) of the control patients displayed positive reactions to the three test antibiotics, whereas the suspected sensitizing drugs elicited a high rate of positive responses (68/90; 76%) in the group of suspected beta-lactam hypersensitive patients. Broken down into symptomatic categories, response to the LMIT was positive in 41 of 58 cases of suspected drug rash (71%), 26 of 26 cases of suspected drug fever (96%), and 20 of 24 cases of suspected drug-induced hepatopathy (83%). Thus, the pyrexial group exhibited a particularly high ratio of positive reactions, and in fact exanthemic cases with concomitant symptoms (eosinophilia, pyrexia, hepatopathy, etc.) also displayed a notably high ratio of positives (19/20; 95%). The overall results indicated that delayed type hypersensitivity (DTH) is largely involved in exanthema, pyrexia and hepatopathy induced by beta-lactam antibiotics, and that the LMIT constitutes an effective means of detecting allergenic drugs in patients with beta-lactam hypersensitivity.

Active participation of eosinophils in patch test reactions to inhalant allergens in patients with atopic dermatitis.

Intracutaneous testing and patch tests with house dust mite and grass pollen allergens were performed in patients with atopic dermatitis. Only patients with an immediate type skin reaction to house dust mite or grass pollen allergens showed a positive patch test reaction to these allergens 24-48 h after testing. Occasionally positive patch test reactions at 20 min, 2 h and 6 h were also observed. Patch test reactions were not found in normal controls or atopic patients without atopic dermatitis. Analysis of the cellular infiltrate demonstrated an influx of eosinophils into the dermis, starting from 2-6 h after patch testing. Immunostaining with antibodies against granular constituents of the eosinophils revealed that the infiltrating eosinophils were in an activated state and had lost part of their granular contents. At 24 h eosinophils also appeared in the epidermis. Electron microscopy showed that in the epidermis, some eosinophils were in close contact with Langerhans cells, suggesting a cell-cell interaction. Taken together, these results strongly suggest an active role for eosinophils in patch test reactions to inhalant allergens in atopic dermatitis patients.

Clinical and immunological responses of cats to feline herpesvirus type 1 infection

Cats which were challenged with feline herpesvirus type 1 developed clinical signs typical of feline viral rhinotracheitis whether or not they had been vaccinated against the disease. However, the clinical disease was less severe and of shorter duration in the vaccinated cats. After challenge, feline herpesvirus type 1 was recovered from the nostrils, oropharynx and peripheral blood leucocytes. Leucocytosis, primarily a neutrophilia, occurred initially in all the cats and was followed after clinical recovery by a mild lymphocytosis. Intradermal skin testing with feline herpesvirus type 1 and cell control antigens produced a positive delayed type skin reaction. Histology of the affected skin 72 hours after injection showed cellular infiltration, predominantly with eosinophils and neutrophils. The severity of the reaction was greater and more prolonged in the skin of the ear than in the skin of the abdomen.

The skin as an immunologic organ: A tribute to Marion B. Sulzberger

The early experiments of Marion B. Sulzberger suggested that the skin played a vital role in the generation of allergic contact dermatitis and other delayed type hypersensitivity reactions. This lecture is presented in the historical context of Dr. Sulzberger's lifework and interest in mechanisms involved in delayed type hypersensitivity. I review recent studies indicating that epidermal Langerhans cells are critical for many immune responses involving the skin and that keratinocytes may also play a role in epidermal immunologic functions in that they secrete factors that may modulate various types of skin reactions. The interaction between these cells and factors and lymphoid cells indicates, as Dr. Sulzberger implied, that the skin should be viewed as an organ of immunity.