Ignite Creation Date:
2024-10-25 @ 7:55 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06652477
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-18
Brief Title:
Evaluation of Desmoglein-3 Autoantibodies in the Tissues of Oral Lichen Planus and Correlation with Disease Severity
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Evaluation of Desmoglein-3 Autoantibodies in the Tissues of AtrophicBullous Erosive Oral Lichen Planus and Correlation with Disease Severity
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
1 evaluate the level of Dsg3 autoantibodies in tissue biopsy of AtrophicBullous Erosive ABE OLP Primary Objective
2 correlate the severity of the disease with the level of tissue Dsg3 autoantibodies Secondary Objective
2 correlate the severity of the disease with the level of tissue Dsg3 autoantibodies Secondary Objective
Detailed Description:
Oral lichen planus OLP a chronic disease and one of the most common dermatoses of the oral mucosa is characterized by white streaks in a lacelike pattern on the tongue andor buccal mucosa The disease is also accompanied by chronic inflammation the degree of which correlates with the intensity of the symptoms
OLP occurs more frequently than the cutaneous form and tends to be more persistent and more resistant to treatment It affects one to two percent of the general adult population with a higher prevalence in the female gender and occurs predominantly in adults over 40 although younger adults and children may be affected
The most common site of oral involvement is the buccal mucosa followed by the tongue and gingiva but any site of the oral mucosa can be affected Clinically OLP is classified as reticular atrophic erosive plaque-type and bullous The reticular pattern is the most common form It is generally asymptomatic and requires no treatment In contrast atrophic-erosive forms usually manifest as erythematous ulcerative lesions associated with symptoms fluctuating from mild burning sensation to severe pain interfering with eating and speaking
Furthermore OLP is considered a potentially malignant disorder with a transformation rate of about 109 with greater risk among those with atrophic-erosive forms
The etiology and pathogenesis of OLP are not completely understood Several factors have been implicated in the etiology and several hypotheses have been proposed for its pathogenesis
It is believed that OLP represents an abnormal immune reaction in which keratinocytes are recognized as an antigen secondary to changes in the antigenicity of the cell surface This elicits an immune response characterized by invasion of inflammatory cells into the subepithelial layer of connective tissue with degeneration of the epithelium of the basement membrane However the antigen or antigens triggering factors have not been identified
Many controversies exist about the pathogenesis of OLP A large body of evidence supports the role of immune dysregulation in the pathogenesis The various mechanisms hypothesized to be involved in immunopathogenesis include humoral immunity antigen-specific cell-mediated immune response non-specific mechanisms and autoimmune response
Humoral immunity has been reported to play a role in the pathogenesis of OLP in addition to the presence of immunoglobulins fibrinogen and C3 complement in the basement membrane at the lesional and perilesional tissue Furthermore concentrations of salivary IgG and IgA subclasses may be changed
Antigen-specific mechanisms in OLP include antigen presentation by basal keratinocytes followed by antigen-specific keratinocyte killing by CD8 cytotoxic T-cells
Non-specific mechanisms include mast cell degranulation and matrix metalloproteinase activation in OLP lesions These mechanisms may combine to cause T-cell accumulation in the superficial lamina propria basement membrane disruption intra-epithelial T-cell migration and keratinocyte apoptosis
The possibility of the presence of circulating antibodies was previously indicated against desmoglein 3 Dsg3 in patients with OLP
Desmogleins Dsgs are the main components of cellular coherence in the epidermis and mucosal surfaces They are consisting of Dsg1 Dsg2 Dsg3 and Dsg4 Dsg3 antigen is expressed in the basement membrane zone of the epidermis keeping the cells from detachment
Dsgs are the victims of autoantibody reaction in some autoimmune bullous diseases such as pemphigus vulgaris and bullous pemphigoid causing disruption of desmosomes and consequent acantholysis
In 2006 Lukac et al demonstrated significantly higher concentrations of circulating autoantibodies against Dsg3 among erosive OLP patients and in patients with reticular OLP
In a recent study including 100 OLP patients 65 of the patients showed the presence of at least one type of autoantibodies in their serum Dsg3 autoantibody was positive in 16 of the patients
Furthermore Saad et al in 2018 showed increased levels of Dsg3 autoantibodies in the serum of patients with erosive OLP at baseline and after the use of topical Tacrolimus 01 The results revealed a statistically significant decrease in the level of Dsg3 autoantibodies during the follow-up period
In 2022 El-Rifaie et al detected that the level of Dsg3 autoantibodies in the serum of OLP patients was significantly higher as compared to normal control persons
However it is difficult to infer whether the anti-Dsg3 autoantibodies in lichen planus are of primary pathogenic significance or are a result of epitope spreading which is known to occur in autoimmune diseases These autoantibodies may be increased as an etiologic agent in OLP or due to inflammatory damage to basal keratinocytes This damage releases the Dsg3 proteins which act as auto-antigens for autoantibodies formation in the circulatory blood
All the studies were concerned with detecting Dsg3 autoantibodies level in the serum of OLP patients Unfortunately such results do not prove the source of Dsg3 autoantibodies to be the OLP lesions Thus the present study will be carried out to detect the level of Dsg3 autoantibodies in tissues affected by atrophicbullous erosive OLP trying to elucidate the actual role of Dsg3 autoantibodies in the etiopathogenesis of OLP
OLP occurs more frequently than the cutaneous form and tends to be more persistent and more resistant to treatment It affects one to two percent of the general adult population with a higher prevalence in the female gender and occurs predominantly in adults over 40 although younger adults and children may be affected
The most common site of oral involvement is the buccal mucosa followed by the tongue and gingiva but any site of the oral mucosa can be affected Clinically OLP is classified as reticular atrophic erosive plaque-type and bullous The reticular pattern is the most common form It is generally asymptomatic and requires no treatment In contrast atrophic-erosive forms usually manifest as erythematous ulcerative lesions associated with symptoms fluctuating from mild burning sensation to severe pain interfering with eating and speaking
Furthermore OLP is considered a potentially malignant disorder with a transformation rate of about 109 with greater risk among those with atrophic-erosive forms
The etiology and pathogenesis of OLP are not completely understood Several factors have been implicated in the etiology and several hypotheses have been proposed for its pathogenesis
It is believed that OLP represents an abnormal immune reaction in which keratinocytes are recognized as an antigen secondary to changes in the antigenicity of the cell surface This elicits an immune response characterized by invasion of inflammatory cells into the subepithelial layer of connective tissue with degeneration of the epithelium of the basement membrane However the antigen or antigens triggering factors have not been identified
Many controversies exist about the pathogenesis of OLP A large body of evidence supports the role of immune dysregulation in the pathogenesis The various mechanisms hypothesized to be involved in immunopathogenesis include humoral immunity antigen-specific cell-mediated immune response non-specific mechanisms and autoimmune response
Humoral immunity has been reported to play a role in the pathogenesis of OLP in addition to the presence of immunoglobulins fibrinogen and C3 complement in the basement membrane at the lesional and perilesional tissue Furthermore concentrations of salivary IgG and IgA subclasses may be changed
Antigen-specific mechanisms in OLP include antigen presentation by basal keratinocytes followed by antigen-specific keratinocyte killing by CD8 cytotoxic T-cells
Non-specific mechanisms include mast cell degranulation and matrix metalloproteinase activation in OLP lesions These mechanisms may combine to cause T-cell accumulation in the superficial lamina propria basement membrane disruption intra-epithelial T-cell migration and keratinocyte apoptosis
The possibility of the presence of circulating antibodies was previously indicated against desmoglein 3 Dsg3 in patients with OLP
Desmogleins Dsgs are the main components of cellular coherence in the epidermis and mucosal surfaces They are consisting of Dsg1 Dsg2 Dsg3 and Dsg4 Dsg3 antigen is expressed in the basement membrane zone of the epidermis keeping the cells from detachment
Dsgs are the victims of autoantibody reaction in some autoimmune bullous diseases such as pemphigus vulgaris and bullous pemphigoid causing disruption of desmosomes and consequent acantholysis
In 2006 Lukac et al demonstrated significantly higher concentrations of circulating autoantibodies against Dsg3 among erosive OLP patients and in patients with reticular OLP
In a recent study including 100 OLP patients 65 of the patients showed the presence of at least one type of autoantibodies in their serum Dsg3 autoantibody was positive in 16 of the patients
Furthermore Saad et al in 2018 showed increased levels of Dsg3 autoantibodies in the serum of patients with erosive OLP at baseline and after the use of topical Tacrolimus 01 The results revealed a statistically significant decrease in the level of Dsg3 autoantibodies during the follow-up period
In 2022 El-Rifaie et al detected that the level of Dsg3 autoantibodies in the serum of OLP patients was significantly higher as compared to normal control persons
However it is difficult to infer whether the anti-Dsg3 autoantibodies in lichen planus are of primary pathogenic significance or are a result of epitope spreading which is known to occur in autoimmune diseases These autoantibodies may be increased as an etiologic agent in OLP or due to inflammatory damage to basal keratinocytes This damage releases the Dsg3 proteins which act as auto-antigens for autoantibodies formation in the circulatory blood
All the studies were concerned with detecting Dsg3 autoantibodies level in the serum of OLP patients Unfortunately such results do not prove the source of Dsg3 autoantibodies to be the OLP lesions Thus the present study will be carried out to detect the level of Dsg3 autoantibodies in tissues affected by atrophicbullous erosive OLP trying to elucidate the actual role of Dsg3 autoantibodies in the etiopathogenesis of OLP
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None