@article{jordan_mamo_olivry_liu_bizikova_2024, title={Re-evaluating the prevalence of anti-desmocollin-1 IgA autoantibodies in canine pemphigus foliaceus}, volume={273}, ISSN={["1873-2534"]}, DOI={10.1016/j.vetimm.2024.110773}, abstractNote={Pemphigus foliaceus (PF) is an autoimmune skin disease of dogs characterized by intraepidermal pustules containing neutrophils and dissociated keratinocytes that develop in association with circulating and tissue-bound IgG autoantibodies. A subset of IgG autoantibodies in canine PF target desmocollin-1 (DSC1), a component of intercellular adhesion complexes within the epidermis. Passive transfer of IgG autoantibodies from canine PF sera to mice was previously shown to induce skin disease in the absence of infiltrating neutrophils. In attempts to identify a mechanism responsible for neutrophil recruitment, past studies evaluated the prevalence of IgA autoantibodies in canine PF sera where they were found in <20% of affected dogs. We re-evaluated the prevalence of anti-DSC1 IgA in canine PF due to concerns regarding the sensitivity of previously used methods. We hypothesized that anti-DSC1 IgA are present in most dogs with PF but have been under-detected due to competition with concurrent anti-DSC1 IgG for binding to their mutual antigenic target. Despite removing approximately 80% of IgG from patient sera using affinity chromatography, we did not detect an increase in anti-DSC1 IgA by performing indirect immunofluorescence on canine DSC1-transfected HEK293T cells. Taken together, our results do not support a role for pathogenic IgA in canine PF.}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Jordan, Tyler J. M. and Mamo, Lisa B. and Olivry, Thierry and Liu, Zhi and Bizikova, Petra}, year={2024}, month={Jul} }
 @article{jing_jordan_li_burette_yang_marinkovich_diaz_googe_thomas_feng_et al._2024, title={Anti-NC16A IgA from Patients with Linear IgA Bullous Dermatosis Induce Neutrophil-Dependent Subepidermal Blistering in Mice}, volume={144}, ISSN={["1523-1747"]}, DOI={10.1016/j.jid.2023.05.027}, abstractNote={Linear IgA bullous dermatosis (LABD) is an acquired autoimmune subepidermal blistering skin disease characterized by circulating and tissue-bound IgA autoantibodies that recognize epitopes within the hemidesmosomal protein BP180, including its NC16A domain. Histologically, LABD has long been defined by neutrophil infiltration and dermal-epidermal separation. However, the pathogenic roles of anti-NC16A IgA and neutrophils in LABD, as well as their interactions, have not been thoroughly studied. We show that passive transfer of patient-derived anti-NC16A IgA induce clinical and histologic LABD pathology in humanized NC16A mice that are reconstituted locally or systemically with human neutrophils. The lesional skin of mice exhibits significantly elevated levels of the neutrophil chemoattractants CXCL-1 and CXCL-2. Furthermore, we show significantly increased levels of the neutrophil chemoattractant IL-8 in blister fluids of LABD patients. This study provides direct evidence that anti-NC16A IgA in LABD patients are pathogenic and interact with neutrophils to mediate tissue injury and subepidermal blister formation. This study further corroborates the importance of neutrophil-mediated tissue injury in LABD disease physiology and establishes a clinically relevant in vivo model system that can be used to systematically dissect the immunopathogenesis of LABD.}, number={1}, journal={JOURNAL OF INVESTIGATIVE DERMATOLOGY}, author={Jing, Ke and Jordan, Tyler J. M. and Li, Ning and Burette, Susan and Yang, Baoqi and Marinkovich, M. Peter and Diaz, Luis A. and Googe, Paul and Thomas, Nancy E. and Feng, Suying and et al.}, year={2024}, month={Jan} }
 @article{jordan_chen_li_burette_wan_chen_culton_geng_googe_thomas_et al._2023, title={The Eotaxin-1/CCR3 Axis and Matrix Metalloproteinase-9 Are Critical in Anti-NC16A IgE-Induced Bullous Pemphigoid}, volume={211}, ISSN={["1550-6606"]}, DOI={10.4049/jimmunol.2300080}, abstractNote={Abstract
               Bullous pemphigoid (BP) is the most common autoimmune bullous skin disease of humans and is characterized by eosinophilic inflammation and circulating and tissue-bound IgG and IgE autoantibodies directed against two hemidesmosomal proteins: BP180 and BP230. The noncollagenous 16A domain (NC16A) of BP180 has been found to contain major epitopes recognized by autoantibodies in BP. We recently established the pathogenicity of anti-NC16A IgE through passive transfer of patient-derived autoantibodies to double-humanized mice that express the human high-affinity IgE receptor, FcεRI, and human NC16A domain (FcεRI/NC16A). In this model, anti-NC16A IgEs recruit eosinophils to mediate tissue injury and clinical disease in FcεRI/NC16A mice. The objective of this study was to characterize the molecular and cellular events that underlie eosinophil recruitment and eosinophil-dependent tissue injury in anti-NC16A IgE-induced BP. We show that anti-NC16A IgEs significantly increase levels of key eosinophil chemoattractants, eotaxin-1 and eotaxin-2, as well as the proteolytic enzyme matrix metalloproteinase-9 (MMP-9) in the lesional skin of FcεRI/NC16A mice. Importantly, neutralization of eotaxin-1, but not eotaxin-2, and blockade of the main eotaxin receptor, CCR3, drastically reduce anti-NC16A IgE-induced disease activity. We further show that anti-NC16A IgE/NC16A immune complexes induce the release of MMP-9 from eosinophils, and that MMP-9–deficient mice are resistant to anti-NC16A IgE-induced BP. Lastly, we find significantly increased levels of eotaxin-1, eotaxin-2, and MMP-9 in blister fluids of BP patients. Taken together, this study establishes the eotaxin-1/CCR3 axis and MMP-9 as key players in anti-NC16A IgE-induced BP and candidate therapeutic targets for future drug development and testing.}, number={8}, journal={JOURNAL OF IMMUNOLOGY}, author={Jordan, Tyler J. M. and Chen, Jinbo and Li, Ning and Burette, Susan and Wan, Li and Chen, Liuqing and Culton, Donna A. and Geng, Songmei and Googe, Paul and Thomas, Nancy E. and et al.}, year={2023}, month={Oct}, pages={1216–1223} }