**7. Genetic factors**

**Loss of "Immune-Privilege" in OLP:** The normal oral epithelium, similar to the eye, testes and placenta, may represent an immune-privileged site, by being able to induce apoptosis of infiltrating T-lymphocytes. In these sites, the stromal cells possess Fas Ligand (CD95L) that can trigger the apoptosis of infiltrating inflammatory and immune cells that express Fas (CD95). [20] Keratinocytes themselves can also trigger T-cell apoptosis by the release of the cytokine TNF-α, which on binding the TNF-receptor-1 of T-cells triggers their apoptosis. Loss or impairment of either of these two mechanisms to induce T-cell apoptosis may have a role

Langerhans cells may also contribute to the loss of self-tolerance. Langerhans cells phagocytose the apoptotic bodies and debris of basal keratinocytes, but in doing so, may process and present to the CD4+ T helper cells a self-antigen derived from the remains of the basal keratinocyte. In turn, this may activate self-reactive CD4+ T cells that differentiate into Th1 or Th2 phenotypes and promote cell- or antibody-mediated autoimmune reactions against basal keratinocytes,

The humoral immune response is thought to have some role in the pathogenesis of OLP, even though it is dominated by the T-cell-mediated immune response. Circulating autoantibodies to desmoglein 1 and 3 have been identified, but again the exact role of such autoantibodies remains uncertain. [23 Further evidence of the potential role of humoral immune response in OLP, is a single case report, dating back to 2008, of full resolution of muco-cutaneous lichen planus with oral and oesophageal involvement, following a course of anti-CD20 monoclonal antibody therapy (rituximab) directed against pre-B and mature B lymphocytes, so preventing

Some of the T-cells in the T-cell dominant lymphocytic infiltrate so pathognomonic for OLP are not specific or targeted. Their presence may be due to pre-existing inflammation that favours the movement of such non-specific T-lymphocytes into the epithelium, which in turn, causes destruction of the keratinocytes. The mechanisms involved include: (1) basement membrane disruption; (2) increased presence of matrix metalloprotienases (MMP); (3) Chemokine (C-C motif) ligand 5 (CCL5) (previously termed RANTES - Regulated on Activa‐ tion, Normal T cell Expressed and Secreted) activity; and (4) Mast cell activation and degra‐

**Basement Membrane Disruption:** Integrity of the epithelial basement membrane is main‐ tained by the keratinocytes, which release collagen IV and laminin V into the basement membrane zone, but the keratinocytes require a basement membrane-derived signal to prevent their apoptosis. Thus, the basement membrane is needed for keratinocyte survival and its

including the stimulation of the cytotoxic T cells against the basal keratinocytes. [14]

in the pathogenesis of OLP.

154 Skin Biopsy - Diagnosis and Treatment

nulation. [14, 15]

**5. Role of the humoral immune response**

their evolution to antibody-releasing plasma cells. [24]

**6. Non-specific immune mechanisms in OLP pathogenesis**

Genetic factors clearly must have a role in the pathogenesis of OLP. Recently, the identification of genetic polymorphisms of cytokine/receptor gene loci has been shown to act as clear-cut genetic risk factors for a number of autoimmune diseases. [29] Polymorphism of several cytokines has been shown to be associated with the clinical presentation of LP. [30] Genetic polymorphisms of the first intron of the promoter gene of interferon-γ and development of oral lesions of LP and an association between the –308A TNF-α allele and the development of cutaneous lesions of LP. [30] The occurrence of OLP has also been linked to MHC class II allele DR6. in those patients who also have HCV. [31] To date no specific HLA antigen profile has been found associated with idiopathic OLP.

be difficult to distinguish from leukoplakia. Oral lesions of lichen planus may also include bullae, but this is rare. These different forms can merge or coexist in the same patient. [1, 34, 35] The commonest sites are inevitably bilateral and include the buccal mucosa (seen in some 90% of patients), gingiva, dorsal tongue, lateral tongue, labial mucosa and the lower lip. Uncommon sites include the palate (Figure 6), upper lip, and floor of the mouth. [34] The gingivae are commonly the site of erythematous/erosive OLP. Involvement of the gingivae is described clinically as desquamative gingivitis, but is not unique to OLP and may feature in

the presentation of other oral dermatoses, especially pemphigoid and pemphigus. [34]

**Figure 2.** a) Reticular OLP (tongue); b) Reticular OLP (buccal mucosa)

**Figure 3.** Paupular OLP

(a) (b)

Oral Lichen Planus

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http://dx.doi.org/10.5772/56482

In summary, despite the oral mucosa only being capable of a limited immunological response, the immuno-pathogenesis of OLP is complex. OLP appears to be predominantly a delayedtype IV hypersensitivity reaction, due in large measure to cytotoxic CD8+ T-lymphocyte induced apoptosis of the basal keratinocytes of the oral epithelium. There are also a number of aspects, best characterised as immune-deregulation that leads to a self -inducing, selfperpetuating cycle that may explain the chronicity of OLP. However, despite a limited comprehension of the pathogenesis of OLP, therapeutic stratagems are being pursued, based on this understanding, including the trialling of TNF-α inhibitors, interleukin-1 inhibitors, mast cells stabiliser agents, to prevent their degranulation, and the use of agents that can induce the up-regulation of key immune-suppressive cytokines such as TGF-β and interleukin-8, or the *in-vitro* production of these cytokines for use as therapeutic agents.
