Epidemiology of patch tested patients with permanent tattoos-A comparative analysis of 9693 IVDK patients (2020-2022).

BACKGROUND: Permanent tattooing is the invasive introduction of tattoo ink (pigments) into the dermis. The ink and aftercare cosmetics applied on pre-damaged skin may contain skin sensitisers. OBJECTIVES: To identify patient characteristics and the pattern of sensitisation in tattooed patients patch tested within the Information Network of Departments of Dermatology (IVDK). PATIENTS AND METHODS: Comparative analysis of patient characteristics and reaction frequencies to baseline series allergens in 1648 consecutive patients with and 8045 consecutive patients without permanent tattoos. Non-overlapping 95%-confidence intervals were considered as significant. RESULTS: Having permanent tattoos was related with female sex, age <40 years, tobacco smoking, atopic dermatitis, (occupational) hand dermatitis and being employed in particular occupational groups (e.g., healthcare workers, mechanics, hairdressers). Sensitisation to nickel was increased in tattooed patients and associated with female sex (OR 4.23 [95%-CI, 3.48-5.18]), age ≥40 years (OR 1.26 [95%-CI, 1.08-1.49]), tobacco smoking (OR 1.19 [95%-CI, 1.01-1.40]) and having permanent tattoos (OR 1.27 [95%-CI, 1.05-1.53]). CONCLUSIONS: The association between nickel sensitisation and permanent tattoos is probably confounded by past reactions to pierced costume jewellery. Socio-economic factors most probably contribute to the connection between tattoos, tobacco smoking, occupational or hand dermatitis, and being employed in particular occupational groups.

Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study.

BACKGROUND: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. OBJECTIVE: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. METHODS: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. RESULTS: An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine. CONCLUSION: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.

Factors increasing the risk for a severe reaction in anaphylaxis: An analysis of data from The European Anaphylaxis Registry.

BACKGROUND: Preventive measures to decrease the frequency and intensity of anaphylactic events are essential to provide optimal care for allergic patients. Aggravating factors may trigger or increase the severity of anaphylaxis and therefore need to be recognized and avoided. OBJECTIVE: To identify and prioritize factors associated with an increased risk of developing severe anaphylaxis. METHODS: Data from the Anaphylaxis Registry (122 centers in 11 European countries) were used in logistic regression models considering existing severity grading systems, elicitors, and symptoms to identify the relative risk of factors on the severity of anaphylaxis. RESULTS: We identified higher age and concomitant mastocytosis (OR: 3.1, CI: 2.6-3.7) as the most important predictors for an increased risk of severe anaphylaxis. Vigorous physical exercise (OR: 1.5, CI: 1.3-1.7), male sex (OR: 1.2, CI: 1.1-1.3), and psychological burden (OR: 1.4, CI: 1.2-1.6) were more often associated with severe reactions. Additionally, intake of beta-blockers (OR: 1.9, CI: 1.5-2.2) and ACE-I (OR: 1.28, CI: 1.05, 1.51) in temporal proximity to allergen exposition was identified as an important factor in logistic regression analysis. CONCLUSION: Our data suggest it may be possible to identify patients who require intensified preventive measures due to their relatively higher risk for severe anaphylaxis by considering endogenous and exogenous factors.

Ethylene oxide as an occupational contact allergen - an underestimated problem?

BACKGROUND: Ethylene oxide (EtO) is a volatile epoxy compound which is used to sterilize medical devices. EtO may cause irritant contact dermatitis, but only few cases of allergic contact dermatitis have been reported yet. OBJECTIVES: About 20 employees of a department for surgery developed eczematous skin reactions at the contact areas to wrist bands of surgical gowns which had been sterilized with EtO. Patch tests were performed to exclude contact allergy. METHODS: Due to the volatility of EtO, patch tests were done with epichlorohydrin (0.1% pet., 1% pet.) which is an epoxy compound chemically related to EtO. RESULTS: 7/8 patients and 4 healthy control persons showed non-allergic irritant reactions to 1.0% epichlorohydrin. 1.0% epichlorohydrin may have induced an iatrogenic sensitization in one of the control persons. None of the control persons reacted to 0.1% epichlorohydrin. Allergic contact dermatitis to EtO and a cross sensitization to epichlorohydrin was diagnosed in a nurse who showed an allergic crescendo patch test reaction to 0.1% epichlorohydrin. CONCLUSIONS: EtO can act as an occupational contact allergen in health personnel, a problem that may have been underestimated in the past due to methodological difficulties in patch testing. When allergic contact dermatitis to EtO is suspected, a patch test to 0.1% epichlorohydrin should be performed.

Characterization of oral immune cells in birch pollen-allergic patients: impact of the oral allergy syndrome and sublingual allergen immunotherapy on antigen-presenting cells.

BACKGROUND: A detailed characterization of human oral immune cells is needed to better understand local mechanisms associated with allergen capture following oral exposure. METHODS: Oral immune cells were characterized by immunohistology and immunofluorescence in biopsies obtained from three healthy individuals and 23 birch pollen-allergic patients with/without oral allergy syndrome (OAS), at baseline and after 5 months of sublingual allergen immunotherapy (AIT). RESULTS: Similar cell subsets (i.e., dendritic cells, mast cells, and T lymphocytes) were detected in oral tissues from healthy and birch pollen-allergic individuals. CD207+ Langerhans cells (LCs) and CD11c+ myeloid dendritic cells (DCs) were found in both the epithelium and the papillary layer of the Lamina propria (LP), whereas CD68+ macrophages, CD117+ mast cells, and CD4+ /CD8+ T cells were rather located in both the papillary and reticular layers of the LP. Patterns of oral immune cells were identical in patients with/without OAS, except lower numbers of CD207+ LCs found in oral tissues from patients with OAS, when compared to OAS- patients (P < 0.05). A 5-month sublingual AIT had a limited impact on oral immune cells, with only a significant increase in IgE+ cells in patients from the active group. Colocalization experiments confirmed that such IgE-expressing cells mostly encompass CD68+ macrophages located in the LP, and to a lesser extent CD207+ LCs in the epithelium. CONCLUSION: Two cell subsets contribute to antigen/allergen uptake in human oral tissues, including (i) CD207+ LCs possibly involved in the physiopathology of OAS and (ii) CD68+ macrophages likely critical in allergen capture via IgE-facilitated mechanisms during sublingual AIT.

Thymic stromal lymphopoietin induction by skin irritation is independent of tumour necrosis factor-α, but supported by interleukin-1.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is an extensively studied cytokine linked to the pathogenesis of allergic diseases, but the inherent activities behind TSLP expression are not well defined. OBJECTIVES: To explore the conditions favourable to TSLP induction outside of a typically allergic set-up and determine the associated mechanisms, and to assess whether TSLP is similarly controlled in murine and human skin. METHODS: A combination of primary keratinocytes, skin explants/epidermal sheets and in vivo strategies was employed. The skin of wild-type and tumour necrosis factor knockout (TNF-/-) mice was subjected to acute irritation. Cells and specimens were stimulated with a range of TSLP inducers in the presence or absence of neutralizing antibodies. TSLP was quantitated by quantitative reverse-transcriptase polymerase chain reaction, enzyme-linked immunosorbent assay and immunohistochemistry. RESULTS: In addition to cytokines, skin irritation brought about by various causes (e.g. shaving, scratching and chemical perturbation) elicited uniformly high-level production of TSLP, which entered the circulatory system. Despite the potency of TNF-α as an in vitro TSLP inducer, the use of TNF-/- mice revealed that this mechanism was completely independent of endogenous TNF-α. Conversely, irritation-elicited TSLP depended on interleukin (IL)-1, which had a more pronounced influence in human skin than in murine skin. Murine and human skin differed considerably regarding TSLP regulation. CONCLUSIONS: Thymic stromal lymphopoietin is a general responder to disrupted skin homeostasis and may have a role in triggering the alarm system of the skin. TSLP induction is rapid, transient and driven by a mechanism that does not involve TNF-α, but partially relies on the evolutionarily ancient IL-1 system. The irritated skin secretes TSLP into the circulatory system. TSLP regulation varies between species.

Guidelines on the use of extracorporeal photopheresis.

BACKGROUND: After the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma was published in 1983 with its subsequent recognition by the FDA for its refractory forms, the technology has shown significant promise in the treatment of other severe and refractory conditions in a multi-disciplinary setting. Among the major studied conditions are graft versus host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection and inflammatory bowel disease. MATERIALS AND METHODS: In order to provide recognized expert practical guidelines for the use of this technology for all indications the European Dermatology Forum (EDF) proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. RESULTS AND CONCLUSION: These guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion.

[Epidemiology of anaphylaxis]. / Epidemiologie der Anaphylaxie.

Anaphylaxis is the most severe manifestation of a mast cell dependent hypersensitivity reaction. Recent data on epidemiology indicate that food and drug induced anaphylaxis has increased within the last years. The epidemiological data on anaphylaxis vary throughout the world as the overall incidence and also relevant elicitors depend on different endogenous, but also exogenous factors (e.g. ICD-code, life style, comorbidities). Data from the anaphylaxis registry has shown that venom, drugs and foods are the most frequent elicitors for anaphylaxis within German-speaking countries, while the ranking of the elicitors is age-dependent. Risk factors for anaphylaxis are comorbidities like asthma or mastocytosis or other circumstances, which can increase either the relative risk or the severity. Further risk factors are age, gender and the concomitant intake of drugs like ACE inhibitors or acetylsalicylic acid but also exercise. Data on the clinical epidemiology of anaphylaxis are essential to follow up the most frequent elicitors and risk factors over time and accumulate data about diagnostic and therapeutic procedures in patients suffering from a potential fatal manifestation of an IgE-dependent disease. The anaphylaxis registry within the German-speaking area achieved to provide data of the most frequent elicitors, risk factors and the medical treatment from affected individuals to optimize the management of patients with anaphylaxis.

Tamoxifen counteracts the allergic immune response and improves allergen-induced dermatitis in mice.

BACKGROUND: Tamoxifen (TX) represents the prototype selective oestrogen receptor modulator. In addition to its use in breast cancer, TX possesses immunomodulatory functions and displays beneficial effects in models of systemic lupus erythematosus. We hypothesized that TX might inhibit type I allergic reactions, which are also characterized by deviations in humoral immunity. OBJECTIVE: To evaluate the effects of TX on the allergic immune response in appropriate mouse models. METHODS: Balb/c mice were sensitized with ovalbumin (OVA)-alum by the intraperitoneal route, and humoral parameters, T cell cytokine patterns and OVA-induced ear swelling responses were determined in a preventive (start of TX treatment before sensitization) and a therapeutic setting (start after sensitization), respectively. In addition, the impact of TX on clinical signs, epidermal thickness and leucocyte infiltration of the skin was investigated in a model of allergen-induced dermatitis. RESULTS: Preventive TX treatment interfered with all aspects of the allergic immune response, leading to a reduction of allergen-specific Ig levels (IgE, IgG1 and IgG2a), a skewing effect in the T cell compartment with the inhibition of IL-4 and an abrogation of ear swelling responses. Interestingly, a therapeutic TX administration was also effective in reducing Ig levels and ear swelling responses. The vigorous systemic effects were additionally mirrored by local changes in allergen-dependent dermatitis with reduced clinical symptoms, diminished epidermal thickness and decreased CD4+ and CD8+ cell infiltrates. CONCLUSION: TX inhibits allergic responses when given preventively and also therapeutically, and improves allergen-induced dermatitis. Because of its effectiveness, TX could bear significant therapeutic potential for the treatment of allergies.

Advances in the management of UVR-associated skin cancers: autoimmune diseases and UV protection.

Ultra violet radiation (UVR) is an important feature for the development or aggravation of several dermatologic diseases. In autoimmune skin diseases it has been suggested as an important cofactor in autoimmune bullous skin diseases and more importantly cutaneous lupus erythematosus (CLE). The pathophysiological role of UVR in CLE is a result of several effects which are triggered by UVR. In detail UVR induces apoptosis of keratinocytes and an abnormal local immune response which triggers inflammation in the skin. These findings result in the clinical approach of a stringent UVR protection in affected patients. Currently UVR protection is advised to patients as a supportive measure but cannot be prescribed to patients as these products are not licensed. Well-defined prospective placebo controlled studies regarding UVR protection are missing.

[Therapy of occupational skin diseases]. / Therapie berufsbedingter Hauterkrankungen.

Hand eczema is one of the most frequent skin diseases. About 5-10% of population has chronic hand eczema. In addition, hand eczema accounts for more than 90% of occupational skin diseases. The therapy of hand eczema is expensive and often leads to a loss in quality of life. The therapy is complex, not always successful and can lead in the worst case to the patient being forced to give up or change their profession. We review the therapeutic options to treat occupational hand eczema.

Association of the toll-like receptor 2 A-16934T promoter polymorphism with severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial pathogenesis and increasing incidence in the Western world. A genetically determined defective function of pattern recognition receptors such as toll-like receptors (TLRs) has been proposed as a candidate mechanism in the pathogenesis of AD. AIM: To study the impact of genetic predisposition of five genes encoding for pattern recognition-related molecules for the phenotype of AD. METHODS: We examined nine different single-nucleotide polymorphism (SNP) frequencies in the genes encoding TLR1, -2, -4, -9 and the adapter molecule TIRAP by PCR with subsequent melting curve analysis in a case/control cohort of 136 adult AD patients and 129 age and gender matched non-atopic, healthy individuals. TLR2-expression and -function in cells from genotyped individuals were analysed. RESULTS: For the SNPs examined, similar genotype frequencies were found in both groups. In a subgroup of patients suffering from severe AD (SCORAD >50), a significantly increased representation of the A-allele in position -16934 of the tlr2 gene was present (P = 0.004). Constitutive tlr2 mRNA expression in peripheral monocytes was independent of this tlr2 promoter SNP. Stimulation assays indicated that IL-6, but not TNF-alpha secretion following TLR2 stimulation is reduced in homozygous tlr2-16934-A allele carriers. CONCLUSION: These data indicate that TLR2 is relevant for the phenotype of severe AD in adults.

Cutaneous side-effects in patients with rheumatic diseases during application of tumour necrosis factor-alpha antagonists.

BACKGROUND: Patients with rheumatic diseases receiving antitumour necrosis factor (TNF)-alpha-based treatment may develop cutaneous reactions. OBJECTIVES: To analyse the new onset or aggravation of skin lesions in patients with a rheumatic disease during treatment with TNF-alpha antagonists. METHODS: We conducted a prospective analysis of 35 of 150 patients with a long history of rheumatic disease, including rheumatoid arthritis, ankylosing spondylitis (Bechterew's disease) and psoriatic arthritis, to test for the development of cutaneous manifestations during anti-TNF-alpha (infliximab, adalimumab or etanercept) treatment. RESULTS: Chronic inflammatory skin diseases such as psoriasis and eczema-like manifestations represented the majority of cases (16 of 35). Cutaneous infections caused by viral, bacterial and fungal agents were also observed in many patients (13 of 35). Skin diseases such as dermatitis herpetiformis, leucocytoclastic vasculitis and alopecia occurred in single cases only. CONCLUSIONS: We observed a broad, diverse clinical spectrum with a majority of chronic inflammatory and infectious skin diseases. However, we did not identify individual risk factors and a discontinuation of the anti-TNF-alpha treatment was not necessary if adequate dermatological treatment was performed. The onset of cutaneous side-effects in anti-TNF-alpha-based treatments should be determined by nationwide registries.

New onset or exacerbation of psoriatic skin lesions in patients with definite rheumatoid arthritis receiving tumour necrosis factor alpha antagonists.

BACKGROUND: Blockage of tumour necrosis factor alpha (TNFalpha) is highly effective in rheumatic diseases, especially in rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis. Furthermore, TNFalpha antagonists have also been shown to significantly reduce psoriatic skin lesions. CASE REPORTS: A series of nine patients with RA who were treated with different types of TNFalpha antagonists and who unexpectedly developed either a new onset or an exacerbation of psoriatic skin lesions are reported.

Retinoic acid inhibits CD40 plus IL-4 mediated IgE production through alterations of sCD23, sCD54 and IL-6 production.

BACKGROUND: All-trans retinoic acid (ATRA) inhibits IgE synthesis from anti-CD40 plus IL-4 stimulated human B lymphocytes. OBJECTIVE: To study the underlying mechanisms, we examined here molecules which are known to have an impact on IgE production, namely CD23, CD54 and IL-6. METHODS: Human anti-CD40 plus IL-4 stimulated B cells were cultured in the absence and presence of ATRA (10(-6)-10(-10) M). ELISAs were performed to determine soluble (s) CD23 and sCD54, IL-6 and IgE-levels. CD23 and CD54 surface expression were determined by flow cytometric analysis. Semiquantitative-RT-PCR was employed to analyse IL-6, CD23 and CD54 mRNA expression. RESULTS: ATRA induced a dose-dependent increase of percent CD23 (3.4 fold) or CD54 (1.6 fold) positive B cells. At the mRNA level, this was reflected by a modest increase of CD54 mRNA (46.5 +/- 15.8%) only. By contrast, levels of sCD54 were decreased dose-dependently in the presence of ATRA (56.6 +/- 7.6%). Cytokine analysis showed that IL-6 secretion was significantly inhibited by ATRA (53.6 +/- 0.6%) and also IL-6 mRNA synthesis was reduced (66.3 +/- 11.6%). The observed inhibition of IgE production mediated by ATRA was significantly reversed to 90.5 +/- 12% by the addition of 100 pg/mL recombinant IL-6. CONCLUSIONS: ATRA interferes through several pathways with the anti-CD40 plus IL-4 mediated B cell activation, namely IL-6, CD23 and CD54.

Subclinical activation of latent cytomegalovirus (CMV) infection and anti-CMV immune response in patients with atopic dermatitis.

BACKGROUND: Microbiological infections are considered to be of pathophysiological importance in atopic dermatitis (AD). As yet, no information is available regarding cytomegalovirus (CMV) infection in this disease. This, however, is of interest because of the high prevalence of latent infections in the general population, the frequent reactivation in inflammatory diseases, and the immunomodulating capacity of CMV. OBJECTIVES: To investigate the prevalence of latent CMV infection, the frequency of active CMV infection, and the immune response to CMV in patients with moderate to severe AD. Methods To detect active infection we analysed CMV antigen expression by peripheral blood mononuclear cells (PBMC) from 27 patients with moderate to severe AD in comparison with 53 healthy volunteers. We used three monoclonal antibodies recognizing different CMV-encoded antigens and immunocytological staining (alkaline phosphatase-antialkaline phosphatase technique). RESULTS: Patients with AD had a higher mean frequency of CMV-positive PBMC: 2.25 per 10 000 vs. 0.74 per 10 000 in controls (P = 0.001) as well as a higher incidence of CMV antigenaemia: 29.6% vs. 7.5% (P < 0.01). Seropositivity for anti-CMV IgG antibodies indicated subclinical activation of latent infection. Remarkably, a clearance of CMV antigenaemia was observed during anti-eczematous treatment. Significantly higher plasma levels of tumour necrosis factor-alpha, which is involved in CMV reactivation, and interleukin-12, which is crucial for an antiviral cellular immune response, were observed in AD patients in comparison with healthy volunteers. Furthermore, a significantly enhanced frequency of circulating activated HLA-DR+ T cells especially in CMV-seropositive AD patients (19.3% vs. 13.5% in seronegative AD patients vs. 10.2% in controls) suggested that the active CMV infection triggers a cellular immune response. This was also supported by a high frequency of CMV-specific interferon-gamma-producing T cells in CMV-seropositive patients with AD. CONCLUSIONS: Our data suggest that active, subclinical CMV infection is more frequent in patients with moderate to severe AD and may have immunopathophysiological relevance.

Effects of retinoids on in vitro and in vivo IgE production.

BACKGROUND: Retinoids modulate the growth and number of different cell types, including B cells. We could previously show that retinoic acid (RA) strongly inhibits CD40 + IL-4-mediated IgE production in vitro. The aim of the present study was to extend these findings regarding the potential use of retinoids for the treatment of allergic diseases. METHODS: In vitro IgE production was studied in anti-CD40 + IL-4-stimulated peripheral blood mononuclear cells (PBMC) from allergic donors in the presence of 10(-15)-10(-5) M all-trans and 13-cis RA and in ovalbumin (OVA)-sensitized BALB/c mice treated with RA (20 mg/kg) before and during sensitization. IgE and IgG1 levels were determined in the sera of the mice at day 21 after 2 injections (days 1 and 8) of aluminum hydroxide-absorbed OVA. RESULTS: All-trans and 13-cis RA inhibited in vitro IgE production from PBMC in a dose-dependent manner, but were more efficient in atopic dermatitis patients with low total serum IgE levels (< 400 kU/ml), maximal inhibition for all-trans RA at 10(-7) M (87%) and for 13-cis RA at 10(-5) M (96%) compared to patients with high serum IgE levels (>2,000 kU/ml), maximal inhibition for both all-trans and 13-cis RA at 10(-5) M (53 and 39%, respectively). In contrast, the in vivo data from OVA-sensitized mice revealed comparable total IgE and IgG1 levels in control versus all-trans RA or CD336-treated groups, specific IgE was even higher in the CD336-treated group (n = 10, 2,814 ng/ml), and was comparable in mice treated with OVA alone or with additional all-trans RA (n = 10, 1,447 and 1,354 ng/ml, respectively). CONCLUSIONS: These results indicate that the efficacy of retinoids to inhibit IgE production in vitro depends on the frequency of switched cells in the peripheral blood and that in an in vivo model using OVA-sensitized mice, retinoids fail to inhibit IgE production.

Expression and functional role of co-stimulatory molecules in CD40+IL-4-stimulated B cells from atopic and non-atopic donors.

As immunological dysregulation is a possible key defect in atopic diseases, we have studied the expression and function of costimulatory molecules in atopic dermatitis (AD) patients compared with normal controls. Using flow cytometry, we showed that CD80 and CD86 are expressed at increased levels on human peripheral B cells in both groups after stimulation with anti-CD40 and interleukin 4 (IL-4), but to a significantly higher extent in the AD group. Furthermore, baseline expression of CD80 and CD86 on peripheral B cells was low in normal donors and increased in AD donors. To study the functional role of the costimulatory molecules in CD40+IL-4-stimulated peripheral mononuclear cells from normal and atopic donors, proliferation and IgE production were analysed in the presence of antibodies against the receptors of the costimulatory molecules. In the presence of either anti-CD28 or anti-CTLA-4, cell proliferation and IgE synthesis were significantly enhanced in the atopic group in anti-CD40+IL-4-stimulated peripheral mononuclear cells. These findings suggest that interaction of CD80 and CD86 with their receptors CD28 and CTLA-4 selectively promotes cell activation, including proliferation and IgE production in CD40+IL-4-stimulated peripheral blood mononuclear cells from atopic donors. It remains to be elucidated whether these changes are primary, based on the genetic background of atopics, or whether they are induced secondarily in the context of atopic pathology.