An immunohistochemical study of oral submucous fibrosis

Abstract

Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity characterized by inflammation and progressive mucosal fibrosis. These reactions may be the result of either direct stimulation from exogenous antigens like areca alkaloids or by changes in tissue antigenicity that may lead to an autoimmune response. This study investigated the presence and distribution of inflammatory cells and MHC class II antigen expression by epithelial and immunocompetent cells using a three-stage immunoperoxidase method on frozen sections. Thirty OSF tissue specimens and ten normal buccal mucosae were studied and compared. All tissues were investigated using antibodies to T cells (CD3), T helper/inducer cells (CD4), T suppressor/ cytotoxic cells (CD8), B cells (CD20), naive T cells and monocytes (CD45RA), macrophages, Langerhans' cells (CD68) and HLA-DR-positive cells (HLA-DR alpha). The predominant cell populations detected in normal tissues were CD3, CD4 and HLA-DR-positive cells. The distribution of CD4-positive cells was similar to that of CD3-positive cells, which were scattered, often uniformly distributed, both in the epithelium and connective tissue. CD8-positive cells were occasionally seen in the normal epithelium and lamina propria. Few scattered B cells (CD20) and macrophages (CD68) were observed in normal mucosa. Naive T cells (CD45RA) were seen in all normal tissues focally concentrated around the connective tissue papillae, with a similar distribution to that of CD3-positive cells. All normal sections showed HLA-DR-positive cells scattered both in the epithelium and in the lamina propria. Epithelial cells did not show any positive reaction to this antibody and many intraepithelial positive cells showed a dendritic morphology. The cell population detected in OSF showed higher numbers of CD3 and HLA-DR-positive cells compared with those of the normal tissues. The pattern of staining for CD4-positive cells in OSF tissues was similar to that of CD3-positive cells both in the epithelium and connective tissue and was higher than that in normal tissues. A few scattered CD8-positive cells and only occasional CD20- and CD68-positive cells were seen in OSF sections. Few CD45RA-positive cells were found in the epithelium and lamina propria of OSF sections. However, OSF specimens showed high numbers of HLA-DR-positive cells in the basal layer of the epithelium, juxtaepithelium and in the lamina propria in a similar distribution to that of CD3 cells compared with the normal tissues. Most HLA-DR-positive cells in the epithelium showed dendrites directed vertically towards the surface. The increased evidence of CD4 and HLA-DR-positive cells in OSF tissues suggests that most lymphocytes were activated and shows an increased presence of Langerhans' cells. The presence of these immunocompetent cells and high ratio of CD4 to CD8 in OSF tissues suggest an ongoing cellular immune response leading to a possible imbalance of immunoregulation and alteration in local tissue architecture.

Angiotensin-converting enzyme gene insertion/deletion polymorphism is associated with risk of oral precancerous lesion in betel quid chewers

“…The increase in CD4 complement and cells with HLA-DR in OSF tissues suggests that most lymphocytes are activated and that the number of Langerhans cells increases. Haque et al (1997) studied subjects with OSF with immunohistochemical methods and found immunocompetent cells to be present in the lesion, with a high ratio of CD4 to CD8 cells. Therefore, they suggested an ongoing cellular immune response leading to a possible imbalance of immunoregulation with eventual local alterations in tissue architecture.…”

Altered Immunohistochemical Expression of Mast Cell Tryptase and Chymase in the Pathogenesis of Oral Submucous Fibrosis and Malignant Transformation of the Overlying Epithelium

“…The cancer stimulating mechanisms operated by MCs include participation in immunosuppression, the release of proangiogenic and mitogenic factors and involvement in the degradation of the extracellular matrix. MCs contain many angiogenic factors and a variety of cytokines, such as histamine, heparin, tryptase, chymase, PDGF, TNF-α, bFGF, TGF-β, IL-6 and vascular endothelial growth factor (VEGF) [21].Upregulation of the above pro-angiogenic cytokines in OSF has already been demonstrated in the literature [22], [23], [24], [25], [62]. The present study demonstrated a statistically significant increase in subepithelial distribution of chymase positive MCs in OSCC group when compared to healthy controls and OSF group.…”

“…MCs are a major source of other pro-fibrotic cytokines like bFGF [15], TGF-β [20], [22], [23], IL-6 [47], and their upregulation has been studied extensively in OSF. Thus, we suggest that a combination of tryptase and chymase along with the various fibrogenic cytokines seems to be an important factor in the development of OSF (Figure.…”

“…MCs produce and store various profibrotic cytokines including transforming growth factor-β (TGFβ) [20], fibroblast growth factor (FGF), platelet derived growth factor (PDGF), interleukin 1 and 6 (IL-1 & IL-6), and tumor necrosis factor–α (TNF-α) [21]. The significance of these profibrotic cytokines in OSF has been studied extensively in the literature [22], [23], [24], [25].…”

Betel quid use in relation to infectious disease outcomes in Cambodia

“…Additionally, several studies have demonstrated that the submucosal fibrosis, oral leukoplakia, and oral erythroplakia that are commonly associated with betel quid, can impair a wide range of immune function parameters (Figure 1), which include but are not limited to: CD3 cells (T lymphocytes), CD4 cells (helper/inducer T lymphocytes), B lymphocytes, macrophages, 25 natural killer cells, 26 total leukocyte and lymphocyte counts, 27 immunoglobulin (Ig) G, IgM, and IgA, 28,29 circulating immune complex, 30 auto-antibodies such as gastric parietal cell antibody (GPCA), thyroid microsomal antibody, anti-nuclear antibody (ANA), anti-reticulin antibody, and anti-smooth muscle antibody (SMA). 31 Thus, under such a level of constant immunosuppression, it is biologically plausible that users experience an increased risk of opportunistic infection transmitted through other means (mosquito bite, food and drink, and risky sexual practices).…”