Intranasally administered antigen 85B gene vaccine in non-replicating human Parainfluenza type 2 virus vector ameliorates mouse atopic dermatitis.

Atopic dermatitis (AD) is a refractory and recurrent inflammatory skin disease. Various factors including heredity, environmental agent, innate and acquired immunity, and skin barrier function participate in the pathogenesis of AD. T -helper (Th) 2-dominant immunological milieu has been suggested in the acute phase of AD. Antigen 85B (Ag85B) is a 30-kDa secretory protein well conserved in Mycobacterium species. Ag85B has strong Th1-type cytokine inducing activity, and is expected to ameliorate Th2 condition in allergic disease. To perform Ag85B function in vivo, effective and less invasive vaccination method is required. Recently, we have established a novel functional virus vector; recombinant human parainfluenza type 2 virus vector (rhPIV2): highly expressive, replication-deficient, and very low-pathogenic vector. In this study, we investigated the efficacy of rhPIV2 engineered to express Ag85B (rhPIV2/Ag85B) in a mouse AD model induced by repeated oxazolone (OX) challenge. Ear swelling, dermal cell infiltrations and serum IgE level were significantly suppressed in the rhPIV2/Ag85B treated mouse group accompanied with elevated IFN-γ and IL-10 mRNA expressions, and suppressed IL-4, TNF-α and MIP-2 mRNA expressions. The treated mice showed no clinical symptom of croup or systemic adverse reactions. The respiratory tract epithelium captured rhPIV2 effectively without remarkable cytotoxic effects. These results suggested that rhPIV2/Ag85B might be a potent therapeutic tool to control allergic disorders.

Evaluation of hypothalamic-pituitary-adrenal axis in patients with atopic dermatitis.

BACKGROUND: Most of the research on atopic dermatitis (AD) has focused on the pathophysiological role of the immune system in AD, and the role of endocrine signals in the pathology of AD has not been explored. Current research has shown a link between the neuroendocrine and immune functions. AIM: The aim was to measure the serum basal cortisol levels and cortisol levels following a low-dose ACTH stimulation test in patients with AD before and after treatment with corticosteroids. METHODS: Three groups of patients with AD were evaluated: mild, moderate, and severe. Basal cortisol levels following an ACTH stimulation test were measured before and after treatment with topical steroids when an improvement in the disease activity by 75% as determined by the SCORAD index was observed. RESULTS: Eighteen patients of the severe group at baseline showed an impaired hypothalamic-pituitary-adrenal (HPA) axis with cortisol levels <250 nmol/l during their first visit. A total of 13 of 18 patients regained their HPA axis activity when the baseline cortisol was measured after using topical corticosteroids which resulted in 75% improvement in the disease activity. CONCLUSIONS: The disease activity rather than the use of topical corticosteroids is responsible for the low basal levels in patients with severe AD.

The role of toll-like receptors in host defenses and their relevance to dermatologic diseases.

The family of toll-like receptors (TLRs) plays a central role in the cutaneous immune defense system. To date, different TLRs have been found on several major cell populations of the skin, such as keratinocytes, fibroblasts, antigen-presenting cells, and melanocytes. Activation of TLRs leads, via different intracellular signaling pathways, to the production of pro-inflammatory stimuli, and is considered a danger signal that should transform the skin in to the functional state of defense. However, TLRs have also been implicated in tissue homeostasis and renewal. Within the group of TLRs, two types have been identified: surface-expressed TLRs, which are predominantly active against bacterial cell wall compounds; and intracellular receptors, which preferentially recognize virus-associated pattern molecules. In addition, surface-expressed receptors trigger phagocytotic and maturation signals, while the intracellular TLRs lead to the induction of antiviral genes. Our review aims to outline the importance of TLRs in the pathogenesis of numerous skin diseases and the potential of TLR agonists as a treatment option for various skin diseases.

Atopic patch testing.

BACKGROUND: Atopic dermatitis is a major problem among the urban population and it can be aggravated or triggered by various allergens. Atopic patch test can be used as a diagnostic tool in characterizing patients with allergen triggered atopic dermatitis. AIMS: 1. Patch testing to reproduce an eczematous reaction by applying prick test allergens under occlusion on intact skin. 2. To find the allergen associated with atopic dermatitis. 3. To find the specific allergen which causes or exacerbates atopic dermatitis in a given subject. METHODS: Seventy five subjects with atopic dermatitis were included in our study and patch tests using prick test allergens were applied to the back. Reading was done after 48 and 72 hours RESULTS: Out of the 75 subjects tested, 47% showed positive reactions, parthenium accounted for 42% of all positive reactions. CONCLUSIONS: Epicutaneous application of prick test antigen on intact skin can produce a reaction. Parthenium is commonest allergen in Bangalore. Counselling based on patch test reports may help to reduce morbidity and improve quality of life.

A study of allergen-specific IgE antibodies in Indian patients of atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing, pruritic dermatitis frequently associated with the hyperproduction of IgE to various allergens. Identification of these allergens is possible by various laboratory investigations. AIM: The present study was designed to assess these allergen-specific antibodies in the diagnosis of AD in the Indian context. METHODS: This prospective study comprised 50 patients of AD. The diagnosis was made clinically after satisfying Hanifin and Rajka's criteria. Serum IgE levels were estimated and specific IgE antibodies were measured for 20 food allergens and aeroallergens. RESULTS: Serum IgE was elevated in 88% of the patients. The highest elevation of mean IgE levels was seen in the 10-20 years age group. Sixty five percent of the children under the age of ten years were positive to one or more food allergens. Food allergens were more often positive in the < or = 10 years age group and specific antibodies to inhalants were seen more frequently in the older age groups. Specific antibodies to apples were found in all age groups. CONCLUSION: Antibodies against apples and hazelnuts were the more commonly seen specific antibodies in children. Incidence of positivity was much higher in children when compared to earlier studies. Identification of food allergens can be an important factor in the diagnosis of AD in children in India. Positivity to inhalant allergens in the older age groups was lower in this study. The allergen profile with regard to inhalants in Indian patients was similar to that of earlier studies.

Eat dirt and avoid atopy: the hygiene hypothesis revisited.

The explosive rise in the incidence of atopic diseases in the Western developed countries can be explained on the basis of the so-called "hygiene hypothesis". In short, it attributes the rising incidence of atopic dermatitis to reduced exposure to various childhood infections and bacterial endotoxins. Reduced exposure to dirt in the clean environment results in a skewed development of the immune system which results in an abnormal allergic response to various environmental allergens which are otherwise innocuous. This article reviews the historical aspects, epidemiological and immunological basis of the hygiene hypothesis and implications for Indian conditions.

T cells and the skin

In addition to its role as a mechanical barrier, the skin plays an important role in temperature regulation, vitamin D synthesis and absorption of ultraviolet radiation. The importance of the skin as an immunological organ was not fully appreciated until the advent of immunosuppressive agents such as cyclosporin and tacrolimus, which have a predominant action against T lymphocytes and have been found to be effective in the management of common skin diseases such as atopic eczema and psoriasis. T lymphocytes are of fundamental importance to the immune system. Access from the vascular compartment into the skin is facilitated by adhesion molecules located on the endothelial of dermal blood vessels. Selective upregulation of adhesion molecules occurs in various inflammatory skin diseases and specific skin homing T lymphocytes preferentially enter the skin rather than other organs. T cell have recently been classified into Th1 and Th2 cells based on their cytokine profile. Th1 cells produce interleukin 2 (IL-2) and interferon gamma, important in macrophage activation and cytotoxity, and Th2 cells produce IL-4 and IL-5, important in B cell maturation and humoral immunity. Contact dermatitis and psoriasis are characterised by Th1 cells and atopic dermatitis by Th2 cells. The Th1/Th2 profile is also important in infectious diseases such as leprosy in which polarisation towards tuberculoid or lepromatous disease depends on a predominance of Th1 or Th2 cells, respectively. Future management of diseases affecting the skin is likely to depend on a greater understanding of the infiltrating T cell subsets and appropriate modulation of the Th1 and Th2 profile.(AU)

Skin manifestations and immunological parameters in childhood food allergy.

According to Hansen's contact rule, the digestive system should be considered as the main shock organ, yet in food allergy, this is not the case. Very often specific food triggers clinical manifestations not involving the digestive system; that is, reactions are manifested either in the respiratory system, as asthma or rhinitis, or in the skin. In these cases the BALT (broncho-alveolar lymphoid tissue) and GALT (gastrointestinal lymphoid tissue) units play a basic role in the sensitizations. The purpose of this study was to determine the most frequent skin manifestations of food allergy among children, and the most frequently involved foods. We also thought it interesting to evaluate the diagnostic reliability of the different standard immunological parameters utilized by the study team in food allergy. All patients underwent intracutaneous tests with 12 groups of the most frequent food allergens, as well as serum IgE, antigen-specific IgE against foods, and antigen-specific histamine release tests. Antigen-specific IgG4 determination was performed in some cases. The results obtained confirmed previous studies, the most common manifestations being: angioedema (48%), followed by urticaria (31%) and atopic dermatitis (21%). Regarding the frequency of sensitization to different food allergens, in mono- or polisensitization, fish and egg stand out in our environment. Certain food allergens are more frequently responsible for specific skin manifestations. Thus, for fish sensitization, the most frequent skin manifestation is atopic dermatitis (50%); for egg sensitization, angioedema is the most frequent skin manifestation (50%); and for milk, urticaria (50%). Finally, and in agreement with previous works regarding the diagnostic reliability of in vitro techniques, we found that the histamine release test offered the highest percentage of diagnostic reliability. Only for sensitization to milk proteins did antigen-specific IgE demonstrate higher reliability. Once again, we stress that our main problem is the lower reliability of skin tests against food allergens than against inhalant allergens. We emphasize the importance of food as a major factor in the etiopathogenesis of atopic dermatitis, as well as the need to complement the study, when possible, by means of the in vitro techniques described.

Evaluation of circulating immune complexes in cutaneous diseases associated with immune disorders.

Several skin diseases associated with immune disorders may be related to the formation of circulating immune complexes (CIC) and their skin deposition. Sera from 20 controls and 108 patients, including: 23 psoriasis, 10 lichen planus, 30 atopic eczemas, 32 cases of leprosy, 10 vasculitis and 3 pyoderma gangrenosum were evaluated for the presence of IgG-containing CIC by the microconsumption complement test (MCT). Additionally, the presence of IgE-containing CIC by means of a polyethylene glycol precipitation and radioimmunoassay technique was evaluated in 10 patients with atopic eczema. It was found that 56.5% of psoriatic patients show moderate CIC concentrations, as well as 34% of leprosy patients, with increased levels when bacillus were detected in skin lesions, and in 90% of leukocytoclastic vasculitis. A close relationship between CIC levels and the clinical evolution of skin lesions was demonstrated in patients with pyoderma gangrenosum and lichen planus. IgG-CIC were detected in 33% and IgE-CIC in 30% of patients with atopic eczema, with the presence of both types of CIC in 2 out of 3 cases. The systematic research on CIC presence in some selected skin diseases shows that immune complexes take part, with different degrees of relevance, in the pathogenesis of all the entities.