Bronchial asthma (BA), atopic dermatitis (AD) and allergic rhinitis (AR) are common atopic disorders with complicated etiologies. The atopic march from early AD to BA, AR, or both later in life and the extensive comorbidity among them indicates, that these atopic disorders might share a common mechanism (1). Moreover, heritability of these atopic disorders is high, being 35-95% for BA, 71-84% for AD, 33-91% for AR and 34-68% for allergen-specific serum immunoglobulin E (IgE) levels (1,2). Filaggrin is now considered as a major predisposing gene for many atopic disorders, which result in a major paradigm in dermatology and allergy research (3). Many studies pointed out an association of the filaggrin gene with different atopic disorders. More specifically, loss-of-function mutations in the filaggrin gene have been reported to have an association with various atopic/allergic disorders (3). Batchelor et al., reported that there is a strong and consistent association between filaggrin mutations and development of AD (4), but Summary Bronchial asthma (BA), atopic dermatitis (AD), and allergic rhinitis (AR) are well known atopic disorders with complex etiologies. This study was undertaken to investigate the role of filaggrin, eosinophil major basic protein (MBP) and leukotriene B4 (LTB4) in patients with BA, AD, and AR. Sera from 1,246 patients with different atopic disorders and 410 normal healthy controls were collected and were evaluated for filaggrin, MBP and LTB4 by specific sandwich ELISAs, whereas immunoglobulin E (IgE) was used as a positive control for atopic patients. Serum analysis showed that filaggrin levels were remarkably high in patients with AD and in patients with multiple (mixed) atopic disorders (p < 0.001), whereas its levels in BA and AR patients were low but much higher than in normal human sera (p < 0.01). MBP levels were also high in AR, BA and mixed atopic patients, whereas AD patients showed no increase of MBP (p > 0.05). In contrast, LTB4 level was found to be significantly low in all tested atopic patients groups as compared to the levels of LTB4 present in normal human sera (p < 0.001). In conclusion, these findings support an association between filaggrin, MBP or LTB4 and atopic disorders. Our data strongly suggest that filaggrin, MBP or LTB4 might be useful in elucidating the mechanisms involved in the pathogenesis of these atopic disorders.

Background and Objective: Oral submucous fibrosis is an inflammatory and a premalignant lesion as classified by "World Health Organization". Its pathogenesis is related to collagen metabolism. Bleomycin is an anti-carcinogenic drug, but it causes pulmonary fibrosis. This study was carried out to study the role of tumor necrosis factor alpha and keratin 17 in pathogenesis of oral submucous fibrosis.Study Design: Fifty pathologically-free female rats were divided into one control group and four test groups. They were injected by phosphate-buffered saline and Bleomycin into the buccal mucosae daily for 2, 4, 6 and 8 weeks, respectively. The histopathological changes was evaluated by studying the changes within epithelium tissue and lamina propria by (H&E) and the expression of both (tumor necrosis factor alpha and keratin 17) using immunohistochemistry and enzyme linked immunosorbent assay respectively. Results:The buccal mucosae of the test groups in comparison with control showed hyperplastic and hyperatrophic epithelial changes that gradually decreased with the severity of oral submucous fibrosis, with epithelial atrophy and focal dysplastic changes, which increase with severity of oral submucous fibrosis gradually. The lamina propria showed gradual increase in inflammatory cells, collagen formation and closure of the blood vessels. Regarding tumor necrosis factor alpha the area percent of immunoexpression, showed the lowest expression in the control and test groups showed gradually increase after 2, 4, 6,8 weeks within epithelium , on the other hand, the area percent of immunoexpression of tumor necrosis factor alpha within lamina propria showed gradually increase after 2, 4, 6 weeks, then decreased after 8 weeks. Regarding Keratin-17, the lowest value was recorded in control group while it increased gradually from the second week to the 8 th weeks. Conclusion:Both protein molecules tumor necrosis factor alpha and keratin 17 appear to be related in case of oral submucous fibrosis. As tumor necrosis factor alpha and keratin 17 are interdependent regulators, they could be used as diagnostic makers and a prognostic mirror of oral submucous fibrosis cases. Tumor necrosis factor alpha inhibitory drugs can be targeted in new therapeutic agents to improve the prognosis of oral submucous fibrosis.