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PubMed1996

Validation of the U.K. diagnostic criteria for atopic dermatitis in a population setting. U.K. Diagnostic Criteria for Atopic Dermatitis Working Party.

One reason why so little is known about the epidemiology of atopic dermatitis (AD) is lack of suitable diagnostic criteria. A simple list of diagnostic criteria for AD for use in epidemiological studies has recently been developed by a U.K. working party. These have performed well in hospital validation studies of subjects with skin diseases. This study sought to validate the newly proposed criteria for AD in a population setting by conducting a cross-sectional survey of 695 schoolchildren aged 3-11 years in three randomly selected primary schools in West Lambeth, London. As a point prevalence measure, the U.K. criteria had a sensitivity of 70%, a specificity of 93%, and a positive predictive value of 47% when compared with a dermatologist's examination findings. Subsequent analysis suggested that most children classified as false positives had suffered from AD in the last year, but were inactive at the time of examination. When adjusted for these cases, the sensitivity and specificity increased to 80 and 97%, respectively, corresponding to positive and negative predictive values of 80 and 97%, respectively. The U.K. diagnostic criteria for AD appear to work well as a 1-year period prevalence measure in London schoolchildren. Further validation in adults and other countries are needed.

Child↗

PubMed2003

The safety and efficacy of tacrolimus therapy in patients younger than 2 years with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease that affects adults and children. Tacrolimus (FK 506) ointment is a recently developed topical immunomodulator that has been approved for use in patients with AD who are older than 2 years. Concern regarding potential systemic toxic effects has limited treatment options for children younger than 2 years. We wanted to determine whether topical tacrolimus therapy is safe and effective in patients with AD who are younger than 2 years. OBSERVATIONS: Twelve patients fitting our criteria who were treated with tacrolimus ointment were identified by retrospective chart review. Data collected included severity of AD, response to therapy, concentration and blood levels of tacrolimus, any adverse effects, and results of laboratory tests, including complete blood cell count, liver function tests, and serum chemistry profiles. As the review was retrospective, baseline laboratory studies were not performed. All the patients experienced improvement in their symptoms, and no significant adverse effects were noted. Nine patients used 0.03% tacrolimus ointment; 3 used 0.1%. All patients had blood levels of tacrolimus that were less than 1.5 ng/mL. There was no apparent difference in tacrolimus levels in patients whether they were treated with 0.03% or 0.1% ointment. Four patients had elevated platelet counts. CONCLUSION: Tacrolimus ointment appears to be effective and safe in the treatment of AD in children younger than 2 years.

Administration, Topical↗

PubMed2002

[Nutritional status of adult patients with atopic dermatitis].

Many atopic dermatitis (AD) patients follow elimination diets for long periods of time because of true or--even more often--suspected food allergies or hypersensitivities. In the present study we investigated the nutritional status of adult AD patients by evaluating food intake protocols followed by measuring different serum parameters. Evaluation of the food intake protocols over 3 days (n = 47) showed that the total calorie intake met recommended intake in 12 patients (group A), ranged between 75-100% of the requirements in 23 patients (group B) and was 50-75% in 12 patients (group C). The relative intake of different nutritional factors approached normal limits in group A and B; the intake of several of these factors was significantly decreased in group C. Various serum parameters in group C patients were different from those found in patients suffering from other chronic skin diseases. Taken together, our results show that a subgroup of AD patients have dietary habits which result in significant nutritional deficiency which are important for homeostasis. This indicates the necessity of professional guidance in these patients in order to only eliminate foods which have been proven to elicit adverse reactions by oral provocation tests.

Adolescent↗

PubMed1985

Psychophysiological analysis of atopic dermatitis.

Ten atopic dermatitis (AD) patients with active symptomatology and ten control subjects matched for age, sex and race were administered a stress test. AD subjects had greater EMG and heart rate activity as well as higher anxiety scores on the Symptom Checklist-90R. These results suggest that AD may have a psychophysiological component.

Adult↗

PubMed2005

The role of dendritic cell subtypes in the pathophysiology of atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory, immunologically mediated skin disease characterized by a T helper type 2 cell-predominant phenotype initially with additional acquisition of T helper type 1 cell phenotype during the chronic eczematous phase. Compelling evidence presented here suggests that two types of dendritic cells (DC), myeloid DC (mDC) and plasmacytoid DC (pDC), are important in the pathogenesis of AD. METHODS: We reviewed the current literature and summarized key information about the role of mDC and pDC in the pathogenesis of AD. RESULTS: Langerhans cells and inflammatory dendritic epidermal cells, which bear the high-affinity receptor for immunoglobulin E on their cell surface, are hypothesized to contribute to the pathogenesis of AD. pDC, Which play an important role in the defence against viral infections, have also been shown to express high-affinity receptor for immunoglobulin E. CONCLUSION: Immunoglobulin E receptor-bearing mDC and pDC subtypes in the blood and the skin of patients with AD are of critical immunologic importance in the complex pathophysiologic network of AD. Targeting mDC and pDC subtypes may lead to effective new therapies for the management of AD.

Chemokines↗

PubMed2004

Effect of an antiallergic drug (Olopatadine hydrochloride) on TARC/CCL17 and MDC/CCL22 production by PBMCs from patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the predominant infiltration of Th2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) and monocyte-derived chemokine (MDC/CCL22) are Th2-type cytokines, and it has been reported that serum CCL17 and CCL22 levels are associated with AD disease activity. Olopatadine hydrochloride (Olopatadine) is an antiallergic drug with selective histamine H(1) receptor antagonist activity. The effect of Olopatadine on chemokine production by peripheral blood mononuclear cells (PBMCs) in AD patients has not been completely elucidated. OBJECTIVES: This study was undertaken to clarify the effects of Olopatadine on CCL17 and CCL22 production by PBMCs from patients with AD during the treatment. METHODS: We measured plasma levels of CCL17, CCL22, IFNgamma, IL-12 and IL-18 in 15 patients with AD before and after treatment with oral Olopatadine (10 mg/day) for 4 weeks. We also examined disease activity using SCORAD index, eosinophil numbers in peripheral blood and serum levels of LDH. PBMCs from the patients were taken before and after the treatment and cultured with or without dust mite allergen extract (DME) for 3 or 5 days. CCL17, CCL22, IFNgamma, IL-12 and IL-18 levels in the supernatants of cultured PBMCs were measured. RESULTS: SCORAD index and eosinophil numbers in peripheral blood significantly decreased during treatment of AD patients with oral Olopatadine and topical corticosteroids for 4 weeks. The plasma levels of CCL17 and CCL22 significantly decreased after the treatment compared with before the treatment (p<0.05) and were significantly correlated with SCORAD index. PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, showed significantly lower levels of CCL17 production than those taken before the treatment (p=0.018). PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, also showed significantly lower levels of IFNgamma production than those taken before the treatment (p=0.012). CONCLUSION: Our data demonstrate that Olopatadine inhibits CCL17 and CCL22 production by PBMCs from AD patients, which are important regulators of Th2 recruitment in the skin.

Adult↗

PubMed2006

Macrophage-derived chemokine (MDC)/CCL22 produced by monocyte derived dendritic cells reflects the disease activity in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a recurrent inflammatory skin disease characterized by high serum levels of IgE and Th2-type cytokines such as IL-4, IL-5 or IL-13. Chemokines attract leukocytes in inflamed tissues. We have previously found that thymus and activation regulated chemokine (TARC)/CCL17 and macrophage-derived chemokine (MDC)/CCL22 are highly secreted in the plasma levels of AD patients. Dendritic cells (DCs) are antigen-presenting cells that are divided into two subgroups including monocyte derived DCs (MoDCs) and plasmacytoid DCs (pDCs). OBJECTIVES: The aim of the study was to elucidate CCL17 and CCL22 production by MoDCs in AD patients, psoriasis vulgaris (PsV) patients and healthy controls (HC). METHODS: MoDCs were obtained from AD patients, PsV patients or HC and were cultured. In addition, the chemokine levels were measured in the supernatants. RESULTS: We found that the CCL22 levels produced by MoDCs in AD patients to be significantly higher than those of PsV patients and HC. There was a significant correlation between the CCL22 levels produced by MoDCs and the SCORAD index. No significant difference in the CCL17 levels produced by MoDCs was detected among AD patients, PsV patients or HC. Immunosuppressive drugs such as dexamethasone (Dex), tacrolimus and cyclosporine (Cys) inhibited the CCL22 production by MoDCs in the AD patients. CONCLUSION: These data suggest that the CCL22 level produced by MoDCs thus reflects the disease activity of AD and it may also play an important role regarding the production of CCL22 in the pathogenesis of AD.

Adolescent↗

PubMed1996

Enhancement of in vitro spontaneous IgE production by topical steroids in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease. Although topical steroids are widely used for AD, management of severe AD is not satisfactory because of relapse or occasional aggravation of symptoms. Moreover, glucocorticoids induce in vitro IgE production. On the other hand, topical sodium cromoglycate (SCG) solution is a safe and effective treatment for AD. METHODS: We treated 43 patients with AD with SCG solution (n = 21) or with topical steroids, beclomethasone dipropionate (BD) ointment (n = 22). After 2 weeks, clinical evaluation and spontaneous immunoglobulin production by peripheral blood B cells or surface IgE+ B cells from patients in the SCG and BD groups were assessed. RESULTS: Both SCG and BD treatment remarkably improved eczema. However, although SCG treatment decreased spontaneous IgE production by B cells without affecting production of IgG, IgM, or IgA, BD treatment selectively increased spontaneous IgE production. SCG treatment also decreased IgE production by surface IgE+ B cells, whereas BD treatment increased it. CONCLUSION: Topical steroid treatment increases in vitro spontaneous IgE production by B cells. This indicated that topical steroids may decrease inflammation; however, a large-scale study on the effect of topical steroids on IgE production in vitro and in vivo may be necessary.

Administration, Topical↗

PubMed1998

In vivo expression of cytokine receptor mRNA in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with immunopathologic features that vary depending on the duration of the lesion. Acute lesions are associated with a T-cell infiltrate and a high expression of IL-4 mRNA compared with chronic lesions, uninvolved AD skin, or skin from normal control subjects. Chronic lesions are rich in eosinophils and monocyte/macrophages and contain a greater number of IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-12 (p40) mRNA-positive cells. OBJECTIVES: In this study, we investigated the mRNA expression of the IL-4 receptor (IL-4Ralpha), IL-5Ralpha, GM-CSFRalpha, and IL-12Rbeta2 in biopsy specimens from acute and chronic AD lesions, uninvolved AD skin, normal skin, and psoriatic skin lesions. METHODS: Cytokine receptor mRNA was examined in paraformaldehyde-fixed biopsy specimens with in situ hybridization with specific antisense riboprobes. RESULTS: Acute and chronic skin lesions exhibited a significant increase in numbers of IL-5Rbeta and GM-CSFRalpha mRNA-positive cells compared with uninvolved AD skin and normal skin (P < .001). Chronic skin lesions had a significantly greater number of IL-5Ralpha and GM-CSFRalpha mRNA-positive cells when compared with acute AD skin (P < .001). In contrast, IL-4Ralpha mRNA expression was increased in acute but not chronic AD lesions compared with uninvolved and normal skin (P < .001). No significant differences were observed in numbers of IL-12Rbeta2 mRNA-positive cells when comparing acute AD, chronic AD, uninvolved AD, and normal skin. In psoriatic skin, the numbers of GM-CSFRalpha and IL-12Rbeta2 mRNA-positive cells were significantly increased compared with acute AD lesions, uninvolved skin, and normal control skin (P < .01). CONCLUSIONS: These results demonstrate that acute AD is associated with a high expression of IL-4Ralpha, whereas IL-5Ralpha and GM-CSFRalpha mRNA are predominantly increased in chronic AD and to lesser extent in acute lesions. These findings support the biphasic role of IL-4, IL-5, and GM-CSF in the pathophysiology of AD.

Adult↗

PubMed1999

Increased production of macrophage migration inhibitory factor by PBMCs of atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disorder. The underlying cause of AD is multifactorial, and several cytokines are considered to be involved in this severe inflammatory skin disease. Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine essential for T-cell activation and delayed-type hypersensitivity. Recently we demonstrated that serum MIF content was significantly elevated in patients with AD. Consistent with this, expression of MIF messenger RNA in keratinocytes of the eczematous skin lesion was up-regulated. OBJECTIVE AND METHOD: Although keratinocytes are considered to be a potential source of increased serum MIF content in AD, precise evaluation has not been carried out in other tissues. MIF is ubiquitously expressed in various cells, including T cells and macrophages. In this study we examined MIF production and its messenger RNA level of PBMCs from patients with AD to investigate the contribution of these cells to elevated serum MIF content and to its pathologic characteristics. RESULTS: Consistent with our previous findings, the serum MIF content of patients with AD was significantly elevated compared with nonatopic healthy control subjects and patients with chronic urticaria without eczema. As for the MIF productivity of unstimulated PBMCs, the MIF content in the culture medium of PBMCs obtained from patients with AD (40.4 +/- 8.4 ng/mL) (mean +/- SEM) was significantly increased compared with that from healthy control subjects (6.6 +/- 1.1 ng/mL) and patients with chronic urticaria (8.5 +/- 1.4 ng/ml) (P <.0001). When PBMCs were stimulated by concanavalin A, MIF production by PBMCs of patients with AD was more enhanced than in control subjects or patients with chronic urticaria. The increased ratio of MIF production by PBMCs in response to concanavalin A was significantly correlated with the severity of clinical features of AD. Supporting these results, the level of MIF mRNA in PMBCs of patients with AD was significantly higher than in nonatopic healthy control subjects. CONCLUSIONS: The current results showed that PBMCs should be an important source of increased serum MIF in AD. Because MIF has the potential to induce local and systemic inflammatory and immune responses, it is conceivable that MIF produced by PBMCs may affect local and systemic pathologic features in AD.

Adolescent↗

PubMed1997

CD4 monoclonal antibody administration in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory dermatosis that probably involves a dysregulated activation of helper T cells, type 2 (Th2 cells). Severe refractory AD can be controlled by cyclosporine treatment. OBJECTIVE: We attempted to determine whether short-term CD4 monoclonal antibody (mAb) therapy could improve severe AD in adults. METHODS: The CD4 mAb, B-F5, was infused over 2 days in three patients with severe refractory AD and, for control purposes, in two patients with severe psoriasis. RESULTS: Administration of B-F5 was well tolerated, despite moderate first dose side effects. Clinical improvement was observed in two patients. In the third patient, a dramatic worsening occurred between 8 and 30 days after treatment, associated with an increased percentage of activated CD4+, CD25+, HLA-DR+, and CD45RO+ cells and peripheral blood eosinophilia. The same CD4 mAb administered to two patients with severe psoriasis induced marked clinical improvement of the lesions. CONCLUSION: Although CD4 mAb infusion may be potentially useful in the treatment of AD, the risk of aggravating the Th1/Th2 imbalance in AD should be considered in the design of future protocols.

Adult↗

PubMed2003

V alpha 24+ natural killer T cells are markedly decreased in atopic dermatitis patients.

Atopic dermatitis (AD) is a common inflammatory skin disease. In AD, cytokines such as interleukin (IL)-4 or interferon (IFN)-gamma are considered to affect the disease status. Recently, human V alpha 24(+) natural killer T (NKT) cells have been found to produce large amounts of IL-4 and IFN-gamma. Thus there is a possibility that the proportion of V alpha 24(+) NKT cells modifies the AD status. In this study, we examine the proportion of the V alpha 24(+)/V beta 11(+) cells that composes the V alpha 24(+) NKT cells in peripheral blood mononuclear cells (PBMCs) from 71 healthy donors (HDs) and 31 AD patients. Because CD4(-) and CD4(+) NKT subsets show different cytokine production patterns concerning IL-4, these two subsets are evaluated. Our results have shown that the proportion of the V alpha 24(+) NKT cells is markedly reduced in AD patients. In addition, the CD4(-) V alpha 24(+) NKT subset has a tendency to be more reduced than the CD4(+) V alpha 24(+) NKT subset. Moreover, the proportion of CD4(-) V alpha 24(+) NKT(+) cells and Th2 deviation of Th1/Th2 balance is inversely correlated. These observations may contribute to the understanding of the mechanism involved in AD.

Adult↗

PubMed2003

Alteration in the production of IL-10 and IL-12 and aberrant expression of CD23, CD83 and CD86 by monocytes or monocyte-derived dendritic cells from atopic dermatitis patients.

Atopic dermatitis (AD) is characterized by the presence of Th2-type cells in the skin infiltration as well as in the peripheral blood, although a predominant infiltration of interferon-gamma (IFN-gamma)-producing cells is also reported in the chronic skin lesions of AD. Recently it has become clear that the development of Th1 or Th2 is strongly influenced by factors produced by the antigen presenting cells (APCs). To clarify whether APCs from AD patients play a favorable role in the differentiation of Th2 cells, we compared the production of cytokines and the expression of co-stimulatory molecules by monocytes (MOs) and monocyte-derived DCs (MoDCs) after stimulations with various reagents between 13 AD patients and 13 age-matched healthy controls. We examined their production of IL-1 beta, IL-10, IL-12p40, and IL-12p70, and their expression of CD23, CD40, CD54, CD80, CD83, CD86 and HLA-DR. We stimulated them with superantigens, lipopolysaccharide (LPS), agonistic anti-CD40 antibody, phytohemagglutinins (PHA), IL-1beta/TNF-alpha, IL-4, or IFN-gamma. The following results were obtained (1): IL-10 production was significantly enhanced in AD MOs after LPS stimulation. In contrast, IL-12p40 production was significantly lower in AD MOs than in HC MOs after a variety of stimulations (2). IL-12p40 was also significantly lower in AD MoDCs after LPS stimulation (3). The induction of CD23 with IL-4 was significantly higher in AD MOs. and finally (4), AD MoDCs augmented the expression of CD83, CD86, and HLA-DR less significantly than HC MoDCs after anti-CD40 Ab stimulation. These data indicate that AD APCs show some responses different from those observed in HC APCs after several stimulations, such as LPS, IL-1 beta/TNF-alpha, IL-4, or anti-CD40 Ab, and that these responses might play a role in the polarizing process of helper T cells into Th2 cells as recognized in AD patients.

Adolescent↗

PubMed2000

Evidence for increased expression of eotaxin and monocyte chemotactic protein-4 in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with tissue eosinophilia and the activation of T lymphocytes. The novel eosinophil chemoattractants, eotaxin and monocyte chemotactic protein (MCP)-4, are up-regulated at sites of allergic inflammation, yet their contribution to the pathophysiologic mechanisms of AD remains to be determined. OBJECTIVE: We sought to investigate the expression of eotaxin and MCP-4 in acute and chronic lesions from patients with AD and to determine their relationship to the numbers of resident inflammatory cells. METHODS: With use of in situ hybridization, the expression of eotaxin and MCP-4 messenger RNA (mRNA) in skin biopsy specimens from patients with acute and chronic AD skin lesions was compared with that of uninvolved skin from these patients and skin from healthy volunteers. RESULTS: There was a constitutive expression of eotaxin and MCP-4 mRNA in skin biopsy specimens from healthy subjects. Positive signal for chemokine mRNA was observed both within the epidermis and inflammatory cells (macrophages, eosinophils, and T cells) of the subepidermis in AD skin lesions. Within the subepithelium acute and chronic skin lesions exhibited a significant increase in the numbers of eotaxin and MCP-4 mRNA-positive cells compared with uninvolved skin (P <.01), whereas the numbers of eotaxin and MCP-4 mRNA-positive cells were significantly higher in chronic AD compared with acute AD skin lesions (P <.005, P <.001, respectively). Correlations were observed between the expression of eotaxin and MCP-4 mRNA and the presence of eosinophils and macrophages, respectively, in AD lesions (r(2) = 0.84, r(2) = 0.94). CONCLUSION: There is an increased expression of eotaxin and MCP-4 in acute and chronic lesions, suggesting that these chemotactic factors play a major role in the pathophysiologic mechanisms of AD.

Biopsy↗

PubMed2001

Topical tacrolimus (FK506) leads to profound phenotypic and functional alterations of epidermal antigen-presenting dendritic cells in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which antigen-presenting epidermal dendritic cells (DCs), ie, Langerhans cells and the so-called inflammatory dendritic epidermal cells (IDECs) expressing the high-affinity receptor for IgE (FcepsilonRI) may play a significant pathophysiologic role. Therapeutic efficacy of the immunosuppressive macrolide tacrolimus (FK506) in AD has been demonstrated in clinical trials, but little is known of its mode of action. OBJECTIVE: The present study focused on the effects of topical tacrolimus treatment on epidermal CD1a+/FcepsilonRI+ DC populations in lesional AD. METHODS: Immunohistological analysis, epidermal DC phenotyping, and functional studies were performed on skin biopsy specimens from treated and untreated lesional skin of 10 patients with AD participating in a clinical trial with tacrolimus. RESULTS: Untreated lesional skin was characterized by a high proportion of CD1a+ cells, which was largely due to a high proportion of IDECs strongly expressing FcepsilonRI. Epidermal DCs isolated from untreated lesional skin exhibited high stimulatory activity toward autologous T cells, which was strongly reduced while clinical improvement was seen during application of tacrolimus. Concomitantly, a decreased FcepsilonRI expression was observed in both Langerhans cells and IDECs. Finally, topical tacrolimus led to a progressive decrease in the IDEC population within the pool of CD1a+ epidermal DCs and also to a decrease in their CD36 expression, which is indicative of lower local inflammation. CONCLUSION: Epidermal CD1a+ DCs may represent a target for topical tacrolimus in the treatment of AD.

Administration, Topical↗

PubMedDate not supplied

Stereological quantification of lymphocytes in skin biopsies from atopic dermatitis patients.

Atopic dermatitis (AD) is histologically characterized by lymphocytic infiltration of the skin and quantitative assessment is required. This study introduces stereological techniques to quantify the number of lymphocytes in skin biopsies. Four-millimetre punch biopsies were taken from skin with active eczema in 8 adults with AD and from clinically normal skin from 4 of the patients. Five persons without allergy or skin disease served as controls. The mean number of lymphocytes in 4-mm skin biopsies was 469,000 and 124,000 in active eczema and in clinically normal skin, respectively. Compared with controls, the number of lymphocytes in biopsies increased by a factor of 6.8 in active eczema and a factor of 1.8 in clinically normal skin. If 20% of skin is affected by eczema the total number of lymphocytes located in the affected skin can be estimated to 1.27 x 10(10). A patient with clinically moderate AD has a considerable number of lymphocytes in the skin.

Adult↗

PubMed1992

IgE-positive Langerhans cells and Th2 allergen-specific T cells in atopic dermatitis.

In atopic dermatitis (AD) IgE-positive Langerhans cells (LC) may be present in the epidermis. These LC are able to capture allergens by means of their specific IgE, inducing an allergen-specific T-cell response in autologous peripheral blood T cells. Epicutaneous patch testing (EPT) may induce an eczematous reaction when IgE is present on the LC. Thus, both in vivo and in vitro, it appears that IgE may be crucial for induction of allergen-specific T-cell responses. Indeed, the cloning of infiltrating T cells from a positive 12-h EPT produced allergen-specific T cells, wheras no in vivo activated bystander T cells have yet been cloned. Moreover, greater than 85% of the T cells cloned were of Th2 phenotype after anti-CD3 and phorbol myristate acetate stimulation, whereas all clones were Th2 after allergen-specific stimulation, and they were able to induce IgE production in normal B cells. This completes the circle of events, because IgE produced by peripheral B cells may bind to LC and facilitate new allergen-specific reactions in the skin.

Allergens↗

PubMed2006

Polymorphisms within the CTLA4 gene are associated with infant atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is one of the most common childhood disorders. It can have a significant impact on the physical and psychological well-being of affected individuals. Although environmental triggers are important, AD also has a strong genetic component. Identifying genes associated with AD may help to understand better the basis of this disorder and its relationship with other allergic disorders such as asthma. OBJECTIVES: Polymorphisms in the gene encoding the inhibitory CTLA4 receptor, an important regulator of T cells, are associated with asthma as well as autoimmune disorders. We have now tested whether polymorphisms in the CTLA4 gene are also associated with early childhood AD. METHODS: A family-based cohort of 112 children and their parents was recruited from Western Sydney, Australia. All children were seen by a paediatric dermatologist and presented with AD within the first 3 years of life. Using the transmission disequilibrium test, individual and haplotypic associations with the +49 and CT60 polymorphisms in exon 1 and the 3' nontranslated DNA of the CTLA4 gene were tested. RESULTS: Single tests of association revealed significant association of the +49(A) [P = 0.037, odds ratio (OR) 1.59, 95% confidence interval (CI) 1-2.55] and borderline significance of the CT60(A) alleles (P = 0.055, OR 1.51, 95% CI 1-2.38). Significant association of the +49(A)/CT60(A) haplotype was detected (P = 0.002, OR 1.78, 95% CI 1.2-2.65). CONCLUSIONS: Polymorphisms within the gene encoding CTLA4 were associated with early onset infant AD. This is in agreement with findings from asthmatic cohorts, suggesting that the +49(A)/CT60(A) haplotype is a genetic risk factor common to asthma and AD.

Adolescent↗