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.

Effect of microbial heat shock proteins on airway inflammation and hyperresponsiveness.

Microbial heat shock proteins (hsp) have been associated with the generation and induction of Th1-type immune responses. We tested the effects of treatment with five different microbial hsp (Mycobacterium leprae, Streptococcus pneumoniae, Helicobacter pylori, bacillus Calmette-Guérin, and Mycobacterium tuberculosis) in a murine model of allergic airway inflammation and airway hyperresponsiveness (AHR). Mice were sensitized to OVA by i.p. injection and then challenged by OVA inhalation. Hsp were administered to each group by i.p. injection before sensitization and challenge. Sensitized and challenged mice developed increased serum levels of OVA-specific IgE with significant airway eosinophilia and heightened responsiveness to methacholine when compared with nonsensitized animals. Administration of M. leprae hsp prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia in a dose-dependent manner. Treatment with M. leprae hsp also resulted in suppression of IL-4 and IL-5 production in bronchoalveolar lavage fluid, while IL-10 and IFN-gamma production were increased. Furthermore, M. leprae hsp treatment significantly suppressed OVA-specific IgE production and goblet cell hyperplasia/mucin hyperproduction. In contrast, treatment with the other hsp failed to prevent changes in airway responsiveness, lung eosinophilia, or cytokine production. Depletion of gamma/delta T lymphocytes before sensitization and challenge abolished the effect of M. leprae hsp treatment on AHR. These results indicate selective and distinctive properties among the hsp, and that M. leprae hsp may have a potential therapeutic role in the treatment of allergic airway inflammation and altered airway function.

IL-18 induction of IgE: dependence on CD4+ T cells, IL-4 and STAT6.

Overproduction of immunoglobulin E (IgE) and T helper cell type 2 (TH2) cytokines, including interleukin 4 (IL-4), IL-5 and IL-13, can result in allergic disorders. Although it is known that IL-4 is critical to the polarization of naïve CD4+ T cells to a TH2 phenotype, both in vitro and in many in vivo systems, other factors that regulate in vivo IL-4 production and TH2 commitment are poorly understood. IL-18, an IL-1-like cytokine that requires cleavage with caspase-1 to become active, was found to increase IgE production in a CD4+ T cells-, IL-4- and STAT6-dependent fashion. IL-18 and T cell receptor-mediated stimulation could induce naïve CD4+ T cells to develop into IL-4-producing cells in vitro. Thus, caspase-1 and IL-18 may be critical in regulation of IgE production in vivo, providing a potential therapeutic target for allergic disorders.

CD1-restricted T-cells influence IgG subclass and IgE production.

BACKGROUND: Human CD1 has recently emerged as a third family of antigen-presenting molecules that is distinct from either major histocompatibility complex class I or class II. OBJECTIVE: We investigated whether the CD1b-restricted T-cell interaction with antigen alters human IgG subclass and IgE isotype production. METHODS: CD1b-restricted antigen-specific T cells derived from the skin lesion of a patient with leprosy were stimulated with their cognate antigen, lipoarabinomman (LAM) of Mycobacterium leprae, in the presence of CD1+ antigen-presenting cells and tested for their ability to alter IgG subclass and IgE production from IgD+ B cells. RESULTS: CD1-restricted T cells cultured with CD1+ antigen-presenting cells in the absence of LAM induced IgG1, IgG3, IgG4, and IgE, whereas CD1b-restricted T cells cultured in the presence of LAM induced IgG1 and IgG3 and inhibited production of IgG4 and IgE. Production of IgG4 and IgE was rescued in the CD1-restricted system by the addition of anti-interferon-gamma. IgG2 production was not induced under any circumstances. CONCLUSION: In this study we demonstrated that a specific CD1b-restricted T-cell line can behave similarly to classically-restricted Th1-type T cells. CD1b-restricted T-cells of this type may regulate immune responses to microbial pathogens by simultaneously enhancing cell-mediated immunity and downregulating IgG4 and IgE responses.

Immunologic aspects of leprosy with special reference to the study of immunoglobulin E.

The serum levels of IgG, IgM, IgD and IgE have been determined in normal subjects, individuals suffering from ascariasis and filariasis, and in leprosy patients. Allergic and parasitic diseases were excluded in these normal subjects and in leprosy patients before they were taken for the study of their serum IgE. The circulating IgG was significantly raised in both tuberculoid and lepromatous forms of leprosy and also in filariasis; IgM was significantly elevated in only the lepromatous form of leprosy, ascariasis as well as in filariasis; while IgA was exclusively raised in both forms of leprosy. IgD was detected in the sera of more subjects with ascariasis and filariasis than in normal individuals and leprosy patients. The mean level of serum IgE in 35 normal Indian subjects was 1,025 I.U. per ml, 9 of them (25%) having serum IgE concentrations above 700 I.U. per ml. The highest mean level of serum IgE was found in ascariasis (7,328 I.U. per ml), followed by leprosy (5,180 I.U. per ml), and filariasis (4,244 I.U. per ml). Furthermore, no significant difference between the mean serum IgE levels of tuberculoid and lepromatous leprosy patients was observed. Although the rise of serum IgE level in these parasitic diseases, as well as in leprosy, was spectacular, the augmented synthesis of this unique class of immunoglobulins was not invariably present in all patients. The results have been discussed on the basis of recent ideas on immunoglobulin synthesis.