Use this URL to cite or link to this record in EThOS:
Title: Novel biomarkers in the diagnosis and pathogenesis of immunobullous disorders
Author: Ali, Sarah Alfarabi
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2016
Availability of Full Text:
Access from EThOS:
Access from Institution:
Mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV) are uncommon mucocutaneous immunobullous disorders associated with significant morbidity. The aims were to: 1) Investigate the potential of saliva for diagnosis and disease-monitoring 2) Utilize serum and salivary biomarkers in the analysis of disease severity and therapeutic responses 3) Correlate phenotypic subgroups with target antigens to potentially explain the spectrum of clinical presentation and disease severity in MMP. Methodology: Matched serum and whole saliva samples were taken from a total of 100 MMP patients, 26 PV patients, 50 healthy controls (HC) and 16 Lichen planus (LP) patients. All LP and PV patients, 40 MMP and 6 HC provided parotid saliva. Reactivity with the NC16a epitope on bullous pemphigoid antigen 2 (BP180), the alpha 6 beta 4 integrin (α6β4) and desmoglein 3 (Dsg3) was determined by Enzyme-linked immunosorbent assays (ELISA). Disease severity was assessed using the Guy’s Oral Disease Severity Score. Results: In MMP, IgG and/or IgA antibody to BP180-NC16a (44%) in whole saliva showed a similar sensitivity to serum (48%). In parotid saliva IgA to BP180-NC16a was positive in 45% and was also secretory component positive (r =0.9141). A change in serum antibodies (IgG and IgA) to BP180-NC16a was significantly related to a change in severity scores (p =0.048 and 0.033, respectively). A positive association was found between 1) the presence of serum IgG to BP180-NC16a and the presence of lesions in multisite disease (p =0.003) and 2) the presence of IgA to BP180-NC16a in whole saliva and the presence of oral and ocular lesions (p =0.016). IgG antibody to α6β4 integrin was positive in 36% of serum and 18% of saliva. Regarding PV, anti-Dsg3 IgG antibody was positive in serum (74%) and whole saliva (61%) with a positive correlation (r =0.9044). Serum IgA anti-Dsg3 antibody was positive in 61% (with a combined IgG positivity of 78% in PV patients). A significant relationship between anti-Dsg3 IgG antibody in whole saliva and therapeutic responses was found (p =0.004). Conclusions: The results show 1) the value of salivary anti-Dsg3 IgG antibodies in monitoring PV patients and confirm the sensitivity and specificity of IgG anti-Dsg3 serum and saliva antibodies in PV diagnosis. The high positivity of serum IgA anti-Dsg3 antibodies requires further elucidation in disease pathogenesis. The salivary biomarkers, IgG and IgA antibodies to BP180-NC16a and α6β4 may be useful in the diagnosis of MMP. 2) IgG and IgA antibodies to BP180-NC16a in serum can be used for disease monitoring and therapeutic responses in MMP. 3) Clinical phenotypes did not appear to be explained by epitope or isotype specificity. However, the novel finding of locally produced antibodies to BP180-NC16a may provide further insight into the pathogenesis of the oral disease. These new findings demonstrate the value of saliva in the diagnosis and monitoring of MMP and for furthering the understanding of disease pathogenesis.
Supervisor: Setterfield, Jane Frances ; Kelly, Charles George ; Challacombe, Stephen James Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available