{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/79855"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/79855","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"The Role of Non-Desmoglein Autoantibodies in Pemphigus Vulgaris","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Sajda, Thomas"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Sinha, Animesh","Microbiology and Immunology"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-07-30T15:10:30Z","date_published":"2019-07-30T15:10:30Z","updated_at":"2026-07-27T19:05:19Z","subjects":["immunology"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/79855","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Sinha, Animesh","Microbiology and Immunology"]},{"key":"dc:creator","label":"Author","values":["Sajda, Thomas"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-07-30T15:10:30Z","2019","2019-01-14 15:13:47"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["immunology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/79855"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Pemphigus vulgaris (PV), a prototypical, humorally-mediated, autoimmune disorder, is a potentially life-threatening skin-blistering disease driven by the production of autoantibodies (autoAbs) directed against keratinocyte antigens. The primary antigenic targets of pathogenic autoAbs are known to be desmoglein 3 (Dsg3), and to a lesser extent desmoglein 1 (Dsg1), which are cadherin family proteins that partially comprise the desmosome, a protein structure responsible for maintaining cell adhesion. Accumulating evidence, however, indicates that anti-Dsg autoAbs alone cannot adequately explain the loss of cell-cell adhesion seen in PV, nor account for disease heterogeneity exhibited across PV patients. Although additional autoAb specificities are known to be present in PV patients, their functional significance is unknown. Large gaps in knowledge currently exist concerning the full scope of pathogenic autoAbs as well as the precise mechanisms through which autoAbs induce blister formation. Consequently, the primary therapeutic interventions for PV focus on systemic immunosuppression, the side effects of which represent a significant health risk to patients. Identification of the full scope of PV autoAbs and subsequent characterization of their functional significance to disease could facilitate the discovery of actionable biomarkers and elucidate the pathogenic mechanisms driving disease, improving prognostics, clinical management and potentially spurring the development of novel therapeutic treatments. To this end, we used protein microarray technology to probe autoAb specificity in PV patients and identified four non-Dsg antigens as primary targets of PV autoAbs. Additionally, we showed that expression of specific genetic elements influenced autoAb specificity. To further this work, we developed an expanded microarray consisting of a broader scope of putative PV antigens and probed autoAb reactivity of 675 serum samples (459 patient, 216 control), the largest such study to date. In addition to confirming the results of our previous study and defining a more comprehensive set of non-Dsg proteins as significant targets of PV autoAbs, we demonstrated that: 1) specific autoAb profiles correlate to both disease activity and morphological phenotype, 2) through longitudinal analysis, autoAb reactivity within a specific patient varied with disease activity status, but the set of antigens recognized differed between patients, and 3) in some instances, autoAb profiles could be used to predict disease activity. Lastly, we explored the functional significance of autoAbs directed against thyroid peroxidase (TPO), previously identified by our work as a primary antigenic target in PV, and demonstrated that anti-TPO autoAbs present in patients can inhibit cell adhesion as well as modulate signaling pathways tightly associated to blister formation in PV. Together, this work suggests that non-Dsg autoAbs may play a functional role in disease and significantly contributes to the current understanding of PV pathogenesis."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The Role of Non-Desmoglein Autoantibodies in Pemphigus Vulgaris"]}]}],"canonical_facts":{"dc:contributor":["Sinha, Animesh","Microbiology and Immunology"],"dc:creator":["Sajda, Thomas"],"dc:date":["2019-07-30T15:10:30Z","2019","2019-01-14 15:13:47"],"dc:description":["Ph.D.","Pemphigus vulgaris (PV), a prototypical, humorally-mediated, autoimmune disorder, is a potentially life-threatening skin-blistering disease driven by the production of autoantibodies (autoAbs) directed against keratinocyte antigens. The primary antigenic targets of pathogenic autoAbs are known to be desmoglein 3 (Dsg3), and to a lesser extent desmoglein 1 (Dsg1), which are cadherin family proteins that partially comprise the desmosome, a protein structure responsible for maintaining cell adhesion. Accumulating evidence, however, indicates that anti-Dsg autoAbs alone cannot adequately explain the loss of cell-cell adhesion seen in PV, nor account for disease heterogeneity exhibited across PV patients. Although additional autoAb specificities are known to be present in PV patients, their functional significance is unknown. Large gaps in knowledge currently exist concerning the full scope of pathogenic autoAbs as well as the precise mechanisms through which autoAbs induce blister formation. Consequently, the primary therapeutic interventions for PV focus on systemic immunosuppression, the side effects of which represent a significant health risk to patients. Identification of the full scope of PV autoAbs and subsequent characterization of their functional significance to disease could facilitate the discovery of actionable biomarkers and elucidate the pathogenic mechanisms driving disease, improving prognostics, clinical management and potentially spurring the development of novel therapeutic treatments. To this end, we used protein microarray technology to probe autoAb specificity in PV patients and identified four non-Dsg antigens as primary targets of PV autoAbs. Additionally, we showed that expression of specific genetic elements influenced autoAb specificity. To further this work, we developed an expanded microarray consisting of a broader scope of putative PV antigens and probed autoAb reactivity of 675 serum samples (459 patient, 216 control), the largest such study to date. In addition to confirming the results of our previous study and defining a more comprehensive set of non-Dsg proteins as significant targets of PV autoAbs, we demonstrated that: 1) specific autoAb profiles correlate to both disease activity and morphological phenotype, 2) through longitudinal analysis, autoAb reactivity within a specific patient varied with disease activity status, but the set of antigens recognized differed between patients, and 3) in some instances, autoAb profiles could be used to predict disease activity. Lastly, we explored the functional significance of autoAbs directed against thyroid peroxidase (TPO), previously identified by our work as a primary antigenic target in PV, and demonstrated that anti-TPO autoAbs present in patients can inhibit cell adhesion as well as modulate signaling pathways tightly associated to blister formation in PV. Together, this work suggests that non-Dsg autoAbs may play a functional role in disease and significantly contributes to the current understanding of PV pathogenesis."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/79855"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["immunology"],"dc:title":["The Role of Non-Desmoglein Autoantibodies in Pemphigus Vulgaris"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:19Z"}