Biomedical subjects

M van Hage-Hamsten

Publications and source records attributed to M van Hage-Hamsten.

At least 55 records · Page 3Linked to original sources

PubMed1999

Vernal keratoconjunctivitis in a Stockholm ophthalmic centre--epidemiological, functional, and immunologic investigations.

PURPOSE: To classify a cohort of 62 patients with vernal keratoconjunctivitis (VKC) in immunologic, functional, and epidemiological terms. METHODS: A retrospective chart review was conducted to establish the patients' ethnic origin and to ascertain the results of standard in vitro and in vivo testing for atopic allergy. The latter data were compared with tear Phadiatop, an allergy screening test, in 31 subjects. Further subgroup analyses included methacholine bronchial provocations, serum screening for chlamydial antibodies and epidemiological calculations of the observed prevalence of VKC in the Stockholm area in 1994. RESULTS: Thirty-seven subjects (59.7%) were sensitised to common allergens. No additional allergic subjects were diagnosed with the tear Phadiatop test. The serology for ocular chlamydial disease was negative. Only 6 out of 17 subjects displayed bronchial reactivity to methacholine of whom 4 had a history of asthma. VKC was clearly more common in individuals with an Asian and African origin. CONCLUSIONS: Sensitivity to allergens is a strong determinant for the disease but in a large proportion of the subjects this immunologic abnormality is absent. The varying prevalence of the condition in different ethnic groups indicates a genetic predisposing factor.

Adolescent↗

PubMed1999

Increasing prevalence of asthma over 12 years among dairy farmers on Gotland, Sweden: storage mites remain dominant allergens.

BACKGROUND: Earlier studies from several countries have shown that IgE-mediated allergy in rural populations is of considerable importance and that storage mites are dominant allergens. OBJECTIVE: In an epidemiological follow-up study among farmers on the island of Gotland, Sweden in 1996 we wished to investigate the prevalence of respiratory allergy and to find out whether storage mites are still important allergens in a farming environment. METHODS: A questionnaire concerning airway symptoms, social and working conditions and smoking habits was distributed to all Gotland farmers aged 15-65 years and was completed by 1577 (86.7%), of whom 1015 were dairy farmers. Based on the answers, 500 dairy farmers were invited to undergo a medical examination which included a skin-prick test (SPT) and blood sampling for RAST analyses. Prevalence figures (symptoms, RAST and SPT) given for the whole population (n = 1015) were based on the investigation of the 461 farmers who took part in the examination. RESULTS: Immediate onset hypersensitivity was present in 41.7% of the 1015 farmers studied, which is almost the same figure as in 1984 (40.0%). The prevalence of asthma had increased significantly during the previous 12 years (5.3% vs 9.8%), as had asthma in combination with rhinoconjunctivitis (3.7% vs 7.0%). Rhinoconjunctivitis, on the other hand, had not changed significantly (36.5% vs 33.1%) and remained one of the most common symptoms. The prevalence of storage mite allergy in the farming population in 1996 was 6.5% and constituted an important cause of allergic symptoms. CONCLUSION: Over 12 years, Gotland dairy farmers have developed significantly more respiratory symptoms from the lower airways, although the proportion with atopy is unchanged. Storage mites are still dominant allergens for developing allergic disease.

Adolescent↗

PubMed1999

Characterization of eosinophils and detection of eotaxin in skin chamber fluid after challenge with relevant allergen in patients with mild asthma.

BACKGROUND: A selective recruitment of eosinophils to sites of allergic inflammation is suggested to be controlled by regulation of cytokines, chemokines and adhesion molecules. OBJECTIVE: The aim of this study was to examine whether allergen challenge in skin chambers, applied on patients with allergic rhinitis and mild asthma, results in a selective influx of activated eosinophils and detectable levels of cytokines/chemokines related to eosinophil recruitment, such as interleukin (IL)-5 and eotaxin. METHODS: A skin blister was induced on the volar aspect of each forearm; one contained PBS-heparin buffer (control) and the other was challenged with relevant allergen. Peripheral blood was drawn before the allergen was applied to the skin chamber, and the expression of CD9, CD11b and EG2-epitope on intracellular eosinophil cationic protein (ECP) was analysed in eosinophils. Chamber fluid was collected 8 h after allergen application and analysed for differential cell counts, expression of eosinophil activity markers, the presence of ECP, eotaxin, and IL-5. RESULTS: The number of recruited leucocytes was equal in the allergen-challenged chambers and in controls. However, the number of eosinophils was significantly increased in the allergen-challenged chambers, and elevated levels of released ECP were measured. Moreover, the eosinophils recruited were activated, as shown by increased expression of EG2 and CD11b, and decreased expression of CD9, in comparison with blood eosinophils. In the skin chamber fluids, higher levels of eotaxin were detected in the allergen-challenged chambers than in controls, but there were no detectable levels of IL-5. CONCLUSION: We have demonstrated a selective recruitment of eosinophils, and higher levels of released ECP and eotaxin, in skin chambers stimulated with allergen, as compared with control chambers. Allergen challenge in skin chambers is a useful tool for studies of eosinophil recruitment, their state of activation, and their involvement in the allergic inflammatory response.

Adult↗

PubMed1999

Identification and characterisation of two allergens from the dust mite Acarus siro, homologous with fatty acid-binding proteins.

BACKGROUND: Dust mites are a major cause of allergic disease worldwide. The dust mite Acarus siro is an inducer of occupational allergy among farmers, but sensitisation has also been found in non-farming populations. METHODS: A degenerate primer was designed to the N-terminal amino acid sequence of a 15-kD IgE-binding protein in A. siro extract. The cDNA sequence was obtained by using reverse transcriptase polymerase chain reaction, standard cloning and sequencing techniques. The protein was expressed in Escherichia coli with a 6-histidine tag at its C-terminus. Immunoblotting of the recombinant protein and whole extract was performed using patient sera. RESULTS AND CONCLUSION: 15 and 17-kD allergens were identified in a fraction of A. siro extract. The cDNA of the 15-kD allergen was isolated, cloned and sequenced and the allergen was expressed as a recombinant protein. The calculated molecular weight of the cDNA-encoded protein is 14.2 kD. The predicted amino acid sequence has one potential N-glycosylation site at position 4-6 and a cytosolic fatty acid-binding protein signature at position 5-22. The protein has 64% sequence identity with Blo t 13, an allergen from the dust mite Blomia tropicalis, as well as homology with several other fatty acid-binding proteins (FABPs) from different organisms. The allergen was named Aca s 13 and was recognised strongly by 3 of 13 (23%) of the subjects investigated. The amino acid sequence of the 17-kD protein was partly determined and it also showed high sequence homology with Blo t 13 and FABPs.

Allergens↗

PubMed1999

Evaluation of specific IgE to the recombinant group 2 mite allergens Lep d 2 and Tyr p 2 in the Pharmacia CAP system.

BACKGROUND: Several recombinant allergens have been shown to be potentially useful for diagnosis of IgE-mediated allergy, but only a few recombinant allergens are at present commercially available in serological assays for detection of specific IgE. The aim of this study was to evaluate the IgE binding to the recombinant major dust mite allergens rLep d 2 and rTyr p 2 and compare it with the IgE binding to the commercial mite extracts Lepidoglyphus destructor and Tyrophagus putrescentiae in the Pharmacia RAST CAP System. METHODS: The recombinant allergens rLep d 2 and rTyr p 2 were immobilised on ImmunoCAPs, and sera from 461 Swedish farmers who are frequently exposed to mites were analysed for specific IgE antibodies. Immunoblotting was performed to evaluate discrepancies between the results obtained with the recombinant and the commercial CAP assays. RESULTS: The IgE values of each recombinant assay significantly correlated with the IgE values of the corresponding commercial CAP assay. The sensitivity of the rLep d 2 assay was 73.3% and that of the rTyr p 2 assay, 60.5% of that provided by the commercial L. destructor and T. putrescentiae assays. Two subjects out of 416, who tested negative in the commercial L. destructor assay, were positive to rLep d 2. The corresponding figures for rTyr p 2 and the T. putrescentiae extract were 5/418. The possibility that these subjects were sensitised to L. destructor and T. putrescentiae could not be excluded. CONCLUSIONS: The data suggest that it may be possible to use rLep d 2 and rTyr p 2 on ImmunoCAPs to detect and quantify IgE antibodies to these, the major allergens of L. destructor and T. putrescentiae. It appears likely that the addition of just a few more recombinant L. destructor and T. putrescentiae allergens in the CAP assay will be sufficient for in vitro diagnosis of IgE mediated allergy to L. destructor and T. putrescentiae.

Allergens↗

PubMed1999

Allergen-induced accumulation of eosinophils and lymphocytes in skin chambers is associated with increased levels of interleukin-4 and sVCAM-1.

BACKGROUND: The aim of the study was to characterize the kinetic accumulation of various inflammatory mediators in allergen-challenged skin chambers applied on patients with pollen-related allergic rhinitis/mild asthma. METHODS: Skin blisters were induced on the forearms and challenged with allergen or phosphate-buffered saline (PBS). Peripheral blood was drawn before and 8 h after challenge for analysis of differential cell counts, sVCAM-1, and alpha2-macroglobulin. Chamber fluids, collected at 1, 4, and 8 h after allergen application, were analyzed for differential cell counts, histamine, interleukin (IL)-4, sVCAM-1, and alpha2-macroglobulin. RESULTS: The number of recruited leukocytes was equal in allergen and PBS chambers; however, the numbers of eosinophils and lymphocytes were significantly (P< or =0.05) elevated in allergen-challenged chambers at 8 h. Compared to PBS chambers, allergen chambers contained significantly (P<0.01-0.05) higher levels of histamine (at 1 and 4 h), IL-4 (at 4 and 8 h), alpha2-macroglobulin (at 1 and 8 h), and sVCAM-1 (at 1 and 8 h). In contrast to alpha2-macroglobulin, levels of sVCAM-1 in peripheral blood were significantly (P<0.05) increased at 8 h. CONCLUSIONS: Increased levels of sVCAM-1 and IL-4 in allergen-challenged chambers, in parallel with increased recruitment of eosinophils and lymphocytes, points to the participation of IL-4 and VCAM-1 in the development of the late-phase reaction. Increased levels of sVCAM-1 in allergen-challenged chambers probably reflects a combination of leakage and local production.

Adult↗

PubMed1998

beta-Tryptase measurements post-mortem in anaphylactic deaths and in controls.

The reliability of measuring mast cell tryptase in post-mortem blood to diagnose anaphylactic deaths has been questioned because moderate elevation of tryptase can be seen also in control cases. Very high tryptase concentrations have been recorded even in a few control cases with known cause of death such as myocardial infarction or trauma. Aiming to compare findings we measured tryptase in 193 cases: 176 with known cause of death, 10 unexplained deaths and seven anaphylactic or anaphylactoid deaths (AADs). Using binary logistic regression we calculated the sensitivity and specificity of the tryptase test at different cut-off values and found 10 micrograms/l to be optimal, the sensitivity being 86% and the specificity 88%. Traumatic deaths (n = 23), sudden infant death syndrome (n = 40) or deaths after heroin-injection (n = 22) showed elevated tryptase values in 35%, 35% and 32%, respectively, and in 40% of the unexplained deaths (n = 10), which was higher than expected (12%). Heart blood tryptase level was elevated in 22% of the controls and femoral blood tryptase in 10%. No correlations were seen with age or post-mortem delay. It is concluded that tryptase measurements are useful in confirming death from AAD, and that blood should be sampled from the femoral vessels. In unexplained deaths tryptase measurement is a useful indicator, but the diagnosis is not to be based on the test alone.

Adult↗

PubMed1998

Cloning and characterisation of a group II allergen from the dust mite Tyrophagus putrescentiae.

The complete cDNA encoding a major allergen from the dust mite Tyrophagus putrescentiae, Tyr p 2, has been sequenced and expressed. A degenerate primer was designed to the N-terminal amino acid sequence of the 16-kDa protein. The complete cDNA sequence was achieved by using reverse transcriptase PCR, PCR+1, standard cloning and sequencing techniques. The cDNA of Tyr p 2 is 552 nucleotides in length from the start codon including 126 nucleotides after the stop codon up to the beginning of the poly(A) tail. The leader sequence consists of 15 amino acids. Regarding the predicted amino acid sequence, there are no potential N-glycosylation sites (N-X-S/T). The sequence showed similarity to group II allergens from other mite species, and some regions are completely conserved. To show that the cloned cDNA sequence was coding for an allergen, Tyr p 2 was expressed in Escherichia coli and shown to react with a T. putrescentiae-positive serum pool.

Allergens↗

PubMed1998

Contribution of disulphide bonds to antigenicity of Lep d 2, the major allergen of the dust mite Lepidoglyphus destructor.

To study the contribution of the 3 disulphide bonds in the major allergen Lep d 2 to the antigenic structure, site-directed mutagenesis was performed. Mutants with one or more cysteine residues altered were constructed with a histidine residue tag for purification purposes and expressed as recombinant proteins in E. coli. Seven mutants were analysed: 3 single mutants (Cys 8, Cys 21 and Cys 72), 3 double mutants (Cys 8-117, Cys 21-16 and Cys 72 77) and one mutant with all 6 cysteines altered (6 Cys). The evaluation of IgE reactivity in 10 allergic patients showed that the disulphide bond formed by cysteine 72 and 77 was the single most contributing bond to IgE binding. Mutants with disruption of the Cys 8-117 bond had a lesser reduction in IgE binding, even though this alteration seemed to influence the compact nature of Lep d 2. However, to abolish the IgE reactivity almost completely, all 6 cysteines had to be altered. A monoclonal antibody previously raised against Lepidoglyphus destructor showed a similar binding as human IgE with no reactivity to the Cys 72 77 or the 6 Cys mutant. Using skin prick test we found no reaction to the 6 Cys mutant at the concentrations tested (1-100 microg/ml) in an Lepidoglyphus destructor allergic patient, while the T-cell reactivity was preserved. The 6 Cys mutant of Lep d 2 may, after further evaluation, be a candidate molecule for improved immunotherapy of Lepidoglyphus destructor allergy.

Allergens↗

PubMed1998

Cytokine production in PBMC from allergics and non-allergics following in vitro allergen stimulation.

Dysregulation of cytokine production in atopic individuals has previously been clearly demonstrated. In the present study we aimed to assess whether a prolonged in vitro exposure of peripheral blood lymphocytes (PBMC) to allergen would result in a, by time, changed cytokine profile in allergic subjects. Blood was taken from 11 atopic asthmatic subjects and nine healthy non-atopic controls during the birch pollen season. PBMC were stimulated with birch pollen allergen (100, 1000 and 10,000 SQ-U/ml). After different times of exposure (1, 3 and 5 weeks) interleukin (IL)-5 and interferon-gamma (IFN-gamma) production was measured. Prior to the IL5 and IFN-gamma determinations, PHA was added to the cultures to ensure maximal release of cytokines. The asthmatic group always displayed a lower IFN-gamma:IL-5 ratio. Significant differences in ratio between the two groups were observed. Furthermore, PBMC challenged in vitro with 10,000 SQ-U/ml resulted in significantly elevated levels of IL-5 in the asthmatic group compared to the control group when determined after 3 and 5 weeks stimulation. In the asthmatic group the balance between IL-5 and IFN-gamma is shifted towards increased IL-5 production following prolonged in vitro stimulation. This might illustrate the in vivo situation, where an increased IL-5 production is of importance in the pathogenesis of asthma.

Adult↗

PubMed1998

Expression of two isoforms of Lep d 2, the major allergen of Lepidoglyphus destructor, in both prokaryotic and eukaryotic systems.

BACKGROUND: The dust mite Lepidoglyphus destructor is a major cause of allergic diseases among farmers. We have previously cloned and sequenced two isoforms of the major allergen Lep d 2 (formerly designated Lep d 1) and found significant homology to group 2 allergens of the house dust mite species Dermatophagoides. We now report on the production and characterization of recombinant Lep d 2. OBJECTIVE: We have expressed both isoforms in two different expression systems; a eukaryotic system, baculovirus in insect cells and a prokaryotic system, E. coli. We have compared the two systems in regard to production yields and immunoreactivity of the recombinant allergens. METHODS: The complete cDNA including the natural leader sequence was cloned into the pBlueBacIII transfer vector, and the rLep d 2 was produced as a secreted protein in baculovirus. For the expression in E. coli, the cDNA was cloned into the pET vector, and the rLep d 2 was produced with six C-terminal histidine residues. The purified recombinant allergens were tested for immunoreactivity with 10 sera from subjects allergic to Lepidoglyphus destructor and were compared with native Lep d 2 using inhibition immunoblotting. The ability of the recombinant allergens to release histamine from basophils was evaluated using a histamine release assay. RESULTS: Both expression systems produced immunoreactive recombinant allergens. They inhibited the binding of human sera to native Lep d 2 confirming their retained IgE binding properties. The yield of pure recombinant protein from the prokaryotic system was approximately 1 mg/L compared to the eukaryotic system which produced up to 4 mg/L in an adherent cell culture system. CONCLUSIONS: We have produced recombinant Lep d 2 in prokaryotic and eukaryotic expression systems which are comparable to the native allergen. Recombinant Lep d 2 might now be included in more extensive clinical studies to confirm its usefulness in the in vitro and the in vivo diagnosis of Lepidoglyphus destructor.

Allergens↗

PubMed1998

Clinical and immunologic aspects of storage mite allergy.

Exposure to storage (nonpyroglyphid) mites has been increasingly recognized as a cause of asthma and rhinitis. Several species have been identified in Europe; e.g., Lepidoglyphus destructor, Acarus farris/siro, Tyrophagus spp., Glycyphagus domesticus, and Blomia tjibodas. Blomia tropicalis, on the other hand, predominates in subtropical and tropical areas. Studies from several countries have shown that IgE-mediated allergy in rural populations is of considerable importance and that storage mites are major allergens. Since these mites are found in homes, especially in regions with damp housing conditions, urban populations are at risk of becoming sensitized. Therefore, sensitization is not restricted only to those with occupational exposure. Several major allergens from storage mites have been identified and characterized. There seems to be a limited allergenic cross-reactivity between storage- and house dust mites. Molecular cloning has demonstrated that the Group 2 allergens from storage mites (Lep d 2 and Tyr p 2) show more than 40% sequence identity with the Group 2 allergens from Dermatophagoides spp. The availability of a large number of recombinant dust mite allergens will make it possible to investigate their homology and the number of allergens required for the diagnosis and treatment of storage mite allergy.

Allergens↗

PubMed1998

IgG subclass antibody responses to birch pollen in sibling pairs discordant for atopy.

Birch pollen allergen specific IgG and IgE antibodies were analysed in the sera of fourteen sibling pairs discordant for atopy. In addition, eight unrelated children free of atopic disease were included in the study. The presence of Bet v 1 specific antibodies in the sera were analysed by an immunoblotting assay. All but one (13/14) of the atopic children had detectable anti-Bet v 1 antibodies of the IgG1 and IgG4 subclasses. The child lacking IgG1 and IgG4 antibodies to Bet v 1 was the only allergic child lacking IgE to Bet v 1. In contrast, only one of the non-atopic siblings (1/14) displayed detectable IgG1 antibodies to Bet v 1. Furthermore, among the non-atopic siblings none (0/14), had detectable IgG4 antibodies to Bet v 1. In the unrelated control group no detectable IgG1 or IgG4 anti-Bet v 1 were detected (0/8). Thus of the non-atopic children only one out of 22 children displayed IgG1 anti-Bet v 1 antibodies. Taken together, it appears that the non-atopic children in general have no/low allergen specific IgG to birch pollen.

Adolescent↗

PubMed1998

No signs of activity markers in peripheral blood despite increased bronchial reactivity after repeated low-dose allergen exposure.

The allergen inhalation test can be used as an experimental model to study pathophysiological events in allergic asthma. Repeated low-dose inhalations of allergen induce increased bronchial hyperresponsiveness (BHR) and resemble natural allergen exposure. The objective of the present study was to investigate whether eosinophil recruitment and activation in peripheral blood, differences in expression of lymphocyte surface antigens and increased bronchial responsiveness to histamine occur during and after repeated low-dose bronchial allergen challenge. Fourteen atopic asthmatic patients were challenged in a randomized double-blind manner for 7 days with either allergen in very low doses or placebo. We measured the concentration of eosinophils, eosinophil cationic protein (ECP) and the expression of the EG2-epitope on intracellular ECP in eosinophils and the expression of lymphocyte surface antigen markers in peripheral blood. The challenge period started and ended with a histamine provocation. The repeated low-dose allergen exposure resulted in a significant increase in BHR. No changes were seen in the placebo group. Concerning the inflammatory parameters in peripheral blood, no significant changes were seen during or after the week of low-dose allergen inhalations. Our results show that very low, repeated doses of allergen induce increased airway reactivity despite lack of evident clinical symptoms or signs of activation of inflammatory cells in peripheral blood.

Adult↗

PubMed1998

T-cell subsets in adenoids and peripheral blood related to age, otitis media with effusion and allergy.

Adenoids and peripheral blood samples from 29 children (20-120 months of age) undergoing adenoidectomy for long-standing otitis media with effusion (OME) (n=16) or obstructive adenoid hyperplasia (n=13) were investigated by flow cytometry for their T-lymphocyte profile. Eleven of the enrolled children were allergic to inhalant and/or food allergens. For the whole group, the percentage of helper T cells belonging to the memory phenotype (CD4+/CD45RO+ cells) was significantly higher in adenoids than in blood (p<0.0001), while the same cell category increased with age in peripheral blood (p<0.01). A highly significant negative regression (p<0.001) was found between age and the percentage ratio of CD4+ cells that were CD45RO+ in adenoids and blood. Allergic children had a higher CD4+/CD8+ ratio for cells expressing CD45RO+ (p<0.05) in adenoids. The results of this study indicate that adenoids participate in the development of an immunological memory. Our findings support a relationship between allergy and memory cells in adenoids.

Adenoids↗

PubMed1998

IgE binding capacity of synthetic and recombinant peptides of the major storage mite (Lepidoglyphus destructor) allergen, Lep d 2.

BACKGROUND: Lepidoglyphus destructor is an important non-pyroglyphid mite species in Europe and a dominant allergen in farming environments. The major allergen of L. destructor, Lep d 2, is a protein of 13.2 kD that is recognised by about 90% of sera RAST positive to this mite species. METHODS: The cDNA of two isoallergens of the Lep d 2 has previously been sequenced and the protein expressed in different protein expression systems. In order to map the B-cell epitopes, the full length protein and the truncated forms of the protein have been expressed in Escherichia coli as glutathione-S-transferase (GST) fusion proteins. Recombinant Lep d 2 fragments and synthetic overlapping 15 mer peptides spanning Lep d 2 were probed with sera from patients allergic to storage mite. RESULTS: The full-length (125 amino acids) GST fusion protein reacted strongly with patient IgE in Western blots and dot blots. Synthetic peptides failed to react with IgE antibodies from mite-allergic patients and the truncated fusion proteins displayed weak IgE-binding capacity. CONCLUSION: We conclude that there are no dominant linear IgE-binding epitopes in Lep d 2. Recombinant or synthetic Lep d 2 fragments may, however, be further evaluated as hypoallergenic candidate molecules for specific immunotherapy.

Allergens↗

PubMed1997

Allergenic characterization of Tyrophagus putrescentiae using sera from occupationally exposed farmers.

BACKGROUND: Allergic sensitivity to storage mites is common in farmers and others who work in environments where hay and grain are handled, stored, or processed. The clinical importance of storage mite-induced allergy in these individuals is generally unknown in the United States. Tyrophagus putrescentiae is a common storage mite, the allergenicity of which has not been characterized. OBJECTIVE: The purpose of this study was to characterize the allergenicity of Tyrophagus putrescentiae. METHODS: Crossed immunoelectrophoresis (CIE) and crossed radioimmunoelectrophoresis (CRIE) were performed to characterize the allergens of this mite using the sera from 24 occupationally exposed farmers RAST-positive to T. putrescentiae. RESULTS: CRIE analysis of T. putrescentiae extract utilizing individual farmers' sera identified 14 allergens. The number of allergens that bound IgE in the individual sera ranged from 5 to 11. Sensitivity to the different allergens varied both within and between patients but 100% of the farmers' sera recognized the same five allergens precipitated by CIE. Fifty percent of patients' sera recognized one additional. Forty-two and 21% of the sera had IgE binding to six and seven of the allergens, respectively. CONCLUSIONS: The results of this study showed that farmers who were occupationally exposed to storage mites had serum IgE specific for many potent allergens from T. putrescentiae. Persons who are exposed to stored product mites in occupational settings or by consumption of food containing these mites are therefore at risk of sensitization and allergic reaction. Increased awareness of sensitivity to this mite in the United States' population is needed.

Allergens↗

PubMed1997

Anaphylactoid shock--a common cause of death in heroin addicts?

We measured mast-cell tryptase in postmortem blood from 22 heroin addicts dying suddenly after injection. In 32%, the concentration of tryptase was elevated (> or = 10 micrograms/l), and the mean value of tryptase was significantly different from a control group dying from known, nonimmunologic causes (P < 0.05). The increased tryptase concentrations indicate that death was preceded by systemic mast-cell degranulation. All victims of drug deaths had morphine in blood, most below 0.2 microgram/ml. In 71% of the victims of drug-related deaths with tryptase values > or = 10 micrograms/l, the intermediate degradation product, 6-monoacetyl-morphine, was not found in blood, whereas this was the case in only two victims with values below that cutoff point. This indicates that those with high tryptase concentrations survived longer than those with lower values. No correlation was found between the IgE levels and tryptase in either group, supporting the hypothesis that tryptase release was not mediated by an allergic reaction. The well-known property of opiates to stimulate unspecifically the liberation of histamine and other constituents of mast-cell granules offers one explanation of our observations. The results suggest that many heroin fatalities are caused by an anaphylactoid reaction.

Adult↗