@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{berg_jacob_mamo_pluta_lunn_2023, title={Refrigerated multi-dose insulin vials remain sterile through 6 months of use}, volume={8}, ISSN={["1748-5827"]}, url={https://doi.org/10.1111/jsap.13664}, DOI={10.1111/jsap.13664}, abstractNote={ObjectivesTo evaluate sterility in refrigerated multi‐dose insulin vials through 6 months of routine aspiration.Materials and MethodsTwelve vials of insulin, six of insulin glargine U100 (Lantus®, 10 mL multi‐dose vial, Sanofi, Bridgewater, NJ) containing the preservative metacresol, and six of protamine zinc insulin U40 (ProZinc®, 10 mL multi‐dose vial, Boehringer Ingelheim, Duluth, GA) containing the preservative phenol, were refrigerated and aspirated twice daily for 6 months, using a new insulin syringe each time. Three vials of each insulin type were wiped with a single‐use alcohol swab before sampling. Three times weekly, aspirated samples were inoculated in Tryptic Soy Broth enrichment media and incubated for evidence of microbial growth. Positive broth was cultured and speciated. Endpoints were microbial vial contamination (defined as three consecutive positive cultures of the same organism) and completion of the six‐month study period.ResultsMicrobial contamination was not identified in any vial throughout the study period. A total of 454 aspirated samples were cultured, one of which exhibited non‐repeatable growth of Staphylococcus epidermidis. This vial was prematurely lost to breakage after 59 culture samples (29 after the positive growth).Clinical SignificanceRefrigerated phenol‐ and metacresol‐containing multi‐dose insulin products carry minimal risk for iatrogenic infection through 6 months of use, regardless of alcohol swab preparation.}, journal={JOURNAL OF SMALL ANIMAL PRACTICE}, author={Berg, A. S. and Jacob, M. E. and Mamo, L. B. and Pluta, D. H. and Lunn, K. F.}, year={2023}, month={Aug} } @article{herrmann_mamo_holmes_mohammed_murphy_bizikova_2022, title={Long-term effects of ciclosporin and oclacitinib on mediators of tolerance, regulatory T-cells, IL-10 and TGF-beta, in dogs with atopic dermatitis}, ISSN={["1365-3164"]}, DOI={10.1111/vde.13140}, abstractNote={AbstractBackgroundAtopic dogs often are managed with allergen‐specific immunotherapy (AIT) and concurrent dosages of ciclosporin (CSA) or oclacitinib to alleviate their clinical signs. Both drugs might affect proper tolerance induction by inhibiting regulatory T‐cell (Treg) induction.Hypothesis/ObjectivesWe evaluated Treg cell numbers and serum interleukin (IL)‐10 and transforming growth factor‐beta (TGF‐β)1 levels in dogs diagnosed with atopic dermatitis (AD) and successfully treated with either CSA or oclacitinib for nine or more months.AnimalsWe included 15 dogs receiving oclacitinib, 14 dogs treated with CSA, 15 healthy dogs, 13 dogs with untreated moderate‐to‐severe AD and 15 atopic dogs controlled with AIT.Materials and MethodsPeripheral blood CD4+CD25+FOXP3+ T‐cell percentages were determined using flow cytometry. Serum concentrations of IL‐10 and TGF‐β1 were measured by enzyme‐linked immunosorbent assay.ResultsThe percentage of Treg cells in the CSA group was significantly lower in comparison with the healthy group (p = 0.0003), the nontreated AD group (p = 0.0056) or the AIT group (p = 0.0186). There was no significant difference in Treg cell percentages between the CSA and oclacitinib groups, nor between the oclacitinib and the healthy, nontreated AD or AIT‐treated dogs. No significant differences were detected in IL‐10 and TGF‐β1 serum concentrations between the five groups.Conclusions and Clinical RelevanceLower Treg cell percentages in the CSA‐treated dogs suggest an impact of this drug on this cell population; however, it does not necessarily mean that it diminishes tolerance. Functionality and cytokine production may be more important than the number of Treg cells. Further studies evaluating the treatment outcome of dogs receiving AIT and concurrent drugs are needed to show clinical relevance.}, journal={VETERINARY DERMATOLOGY}, author={Herrmann, Ina and Mamo, Lisa B. and Holmes, Jenny and Mohammed, Javid P. and Murphy, K. Marcia and Bizikova, Petra}, year={2022}, month={Dec} } @article{bizikova_linder_mamo_2022, title={Trunk-dominant and classic facial pemphigus foliaceus in dogs - comparison of anti-desmocollin-1 and anti-desmoglein-1 autoantibodies and clinical presentations}, ISSN={["1365-3164"]}, DOI={10.1111/vde.13094}, abstractNote={AbstractBackgroundCanine trunk‐dominant pemphigus foliaceus (PF) is mentioned rarely in the literature.Hypothesis/ObjectivesThe goal of this study was to provide clinical description of trunk‐dominant PF and to demonstrate the prevalence of serum antikeratinocyte, anti‐desmocollin‐1 (DSC1) and anti‐desmoglein‐1 (DSG1) antibodies, and determine their diagnostic value in this particular PF phenotype.Materials and methodsClinically relevant information was collected from 31, 25 and 34 dogs with trunk‐dominant and facial PF and superficial pyoderma (SP), respectively. Sera from these dogs were tested for antikeratinocyte, anti‐DSC1 and anti‐DSG1 antibodies using indirect immunofluorescence on canine tissues and DSC1‐ and DSG1‐transfected cells. Sera from healthy dogs and dogs with clinically irrelevant diseases served as controls.ResultsFootpad involvement and grouped/polycyclic lesion organisation were identified as features of both PF phenotypes, and not of SP. Antikeratinocyte immunoglobulin (Ig)G was not specific for canine PF. By contrast, antigen‐specific IgG was detected only in PF sera; anti‐DSC1 IgG in 100% and 58% of dogs with facial and trunk‐dominant PF, respectively, and anti‐DSG1 IgG in 7% of dogs with trunk‐dominant PF only.ConclusionsTrunk‐dominant PF shares DSC1 as a major autoantigen with facial PF. The ability to detect anti‐DSC1 IgG is lower in trunk‐dominant PF, yet despite the lower sensitivity, the positive predictive value and accuracy of this particular anti‐DSC1 IgG test are high. A negative test result, however, cannot exclude the diagnosis, and characteristic clinical features such as footpad involvement and/or grouped/polycyclic lesions must be considered when distinguishing trunk‐dominant PF from its most relevant differential diagnosis: SP.}, journal={VETERINARY DERMATOLOGY}, author={Bizikova, Petra and Linder, Keith E. and Mamo, Lisa B.}, year={2022}, month={Jun} } @article{levy_linder_mamo_herrmann_bizikova_2020, title={Cutaneous polyautoimmunity in two unrelated dogs: pemphigus foliaceus and generalized discoid lupus erythematosus}, volume={31}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12851}, abstractNote={BackgroundPolyautoimmunity, the concurrent expression of two or more distinct autoimmune diseases (ADs) in a single individual, is a known phenomenon in humans and has been rarely reported in dogs. To the best of the authors’ knowledge, comorbid pemphigus foliaceus (PF) and generalized discoid lupus erythematosus (GDLE) has not been reported in dogs.Hypothesis/ObjectivesTo describe the clinical, histological and immunological features and treatment outcome of two unrelated dogs with comorbid PF and GDLE.AnimalsOne 10‐year‐old, spayed German shepherd dog and one 8‐year‐old, castrated American Staffordshire terrier presented for evaluation of a symmetrical, facial‐ and/or pedal‐dominant pustular dermatitis with concurrent, truncal scaly plaques.MethodsFor each dog, clinicopathological characterization included physical examination, lesion cytological evaluation, bacterial culture and sensitivity testing, skin histopathological investigation and direct and indirect immunofluorescence testing. Additional diagnostic imaging and haematological testing was performed to exclude extracutaneous disease.ResultsBoth dogs exhibited lesions clinically and histologically compatible with PF and GDLE. Moreover, one dog exhibited generalized leucotrichia and chronic superficial keratitis. Remission was achieved with immunosuppressive dosages of prednisolone [high‐dose pulse (Case 1) or standard immunosuppressive dosage (Case 2)] and ciclosporin (5–6 mg/kg/day). Tissue‐bound antikeratinocyte immunoglobulin (Ig)G and IgM were detected in both dogs. A weak basement membrane zone deposit of C3 was seen in one dog. Circulating antikeratinocyte and anti‐desmocollin‐1 IgG were detected in one dog.Conclusions and clinical importanceCutaneous polyautoimmunity can occur in the dog. Depending on the specific disease combinations, overlapping clinical features may present diagnostic and/or therapeutic challenges. Moreover, these cases should be monitored for development of additional cutaneous or extra‐cutaneous AD(s).}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Levy, Britt J. and Linder, Keith E. and Mamo, Lisa B. and Herrmann, Ina and Bizikova, Petra}, year={2020}, month={Aug}, pages={325-+} } @article{levy_mamo_bizikova_2020, title={Detection of circulating anti-keratinocyte autoantibodies in feline pemphigus foliaceus}, volume={31}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12861}, abstractNote={BackgroundCirculating anti‐keratinocyte immunoglobulin (Ig)G targeting desmosomal proteins have been identified in people and dogs with pemphigus foliaceus (PF). By contrast, detection attempts in PF‐affected cats have been largely unsuccessful.Hypothesis/ObjectivesTo detect circulating anti‐keratinocyte autoantibodies in PF‐affected cats and determine their titres and tissue‐staining patterns.AnimalsThirty PF‐affected cats were compared to 11 specific‐pathogen free, 15 healthy and 31 allergic cats.Methods and materialsSera were tested by indirect immunofluorescence on canine footpad and buccal mucosal substrates.ResultsCirculating, anti‐keratinocyte IgG with a suprabasilar, web‐like (intercellular) pattern were detected in the majority of PF‐affected cats (23 of 30, 77%), some allergic cats (six of 31, 19%) and one healthy cat (7%). Both footpad epidermis and buccal mucosa were positive in the majority of seropositive PF‐affected cats (21 of 23, 91%), and in only one of six (17%) seropositive allergic cats. Staining was limited to the footpad in the remaining seropositive PF‐affected and allergic cats and one seropositive healthy cat. Reciprocal IgG titres were significantly higher in PF‐affected cats compared to controls (Dunn’s post‐test, P < 0.0001). Anti‐keratinocyte IgM, IgA or IgE were not detected in any sera.Conclusions and clinical importanceThese results confirm the presence of circulating anti‐keratinocyte IgG in a majority of PF‐affected cats and in a small percentage of healthy and allergic cats. Although the molecular target and pathogenic nature of the antibodies remains unknown, the detection of positive immunostaining on buccal mucosal tissue, in addition to the footpad, suggests that the major target antigen of feline PF differs from that reported in dogs.}, number={5}, journal={VETERINARY DERMATOLOGY}, author={Levy, Britt J. and Mamo, Lisa B. and Bizikova, Petra}, year={2020}, month={Oct}, pages={378-+} } @article{high_linder_mamo_levy_herrmann_bizikova_2020, title={Rapid response of hyperkeratotic erythema multiforme to oclacitinib in two dogs}, volume={31}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12852}, abstractNote={BackgroundHyperkeratotic erythema multiforme (HKEM) is a clinically distinct dermatosis and poorly characterized syndrome, comprised of hyperkeratotic plaques with variable symmetry and apoptosis similar to “classic” erosive canine EM. Hyperkeratotic EM has a protracted clinical course and, although treatments with glucocorticoids, azathioprine and/or ciclosporin have been tried, rates of remission are low.ObjectivesTo describe successful treatment of HKEM in two dogs using oclacitinib.AnimalsA 7‐year‐old, spayed Havanese dog (Case 1) and a 1‐year‐old, intact cryptorchid Dachshund dog (Case 2).MethodsCase characterization and clinical diagnoses were based on lesion character, surgical biopsy, cytological evaluation, culture, direct immunofluorescence (DIF) and expected responses to treatments.ResultsBoth cases exhibited multifocal, often symmetrical hyperkeratotic plaques with adherent scale. Histological findings revealed prominent epidermal hyperplasia, parakeratotic hyperkeratosis, lymphocytic dermatitis and transepidermal apoptosis with lymphocytic satellitosis. DIF revealed fine, patchy IgG, IgM and IgA basement membrane deposits (Case 2). Both dogs exhibited rapid improvement with oral oclacitinib (0.6–0.9 mg/kg twice daily) with a complete remission of clinical signs observed in 12 and seven weeks in cases 1 and 2, respectively.Conclusion and Clinical ImportanceOclacitinib could be considered as a fast‐acting and effective treatment option for HKEM in dogs.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={High, Endya J. and Linder, Keith E. and Mamo, Lisa B. and Levy, Britt J. and Herrmann, Ina and Bizikova, Petra}, year={2020}, month={Aug}, pages={330-+} } @article{bizikova_linder_wofford_mamo_dunston_olivry_2015, title={Canine epidermolysis bullosa acquisita: A retrospective study of 20 cases}, volume={26}, number={6}, journal={Veterinary Dermatology}, author={Bizikova, P. and Linder, K. E. and Wofford, J. A. and Mamo, L. B. and Dunston, S. M. and Olivry, T.}, year={2015}, pages={441-} } @article{bizikova_olivry_mamo_dunston_2014, title={Serum autoantibody profiles of IgA, IgE and IgM in canine pemphigus foliaceus}, volume={25}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84911375280&partnerID=MN8TOARS}, DOI={10.1111/vde.12143}, abstractNote={BackgroundPemphigus foliaceus (PF) is the most common IgG‐mediated autoimmune skin disease in dogs. Studies of human PF have revealed the presence of other antigen‐specific autoantibody isotypes, thereby uncovering new avenues of investigation of the disease pathomechanism.Hypothesis/ObjectivesThe aim was to obtain information about the autoantibody isotype response in canine PF.MethodsSera from 34 dogs with PF were tested for the presence of antikeratinocyte, anti‐desmocollin‐1 and anti‐desmoglein‐1 IgA, IgE and IgM using indirect immunofluorescence.ResultsUsing our indirect immunofluorescence technique, IgA, IgE and IgM autoreactivities were detected in six, one and zero of 34 sera from PF‐affected dogs, respectively. Two of the six IgA‐positive sera contained antikeratinocyte and anti‐desmocollin‐1 IgA, while the four remaining sera tested positive either for antikeratinocyte IgA (two of six) or for anti‐desmocollin‐1 IgA (two of six). A single serum contained anti‐desmocollin‐1 IgE. None of the six sera from healthy dogs contained detectable IgA, IgE or IgM autoantibodies.Conclusions and clinical importanceOur findings suggest that sera from dogs with PF rarely contain IgA or IgE autoantibodies at levels detectable by indirect immunofluorescence, while IgM autoreactivity appears not to be a feature of this disease. Considering these findings, it appears that canine PF is aetiologically and immunologically similar to that of the classic human PF, in which the IgG autoantibody response is also the predominant type.}, number={5}, journal={VETERINARY DERMATOLOGY}, author={Bizikova, Petra and Olivry, Thierry and Mamo, Lisa B. and Dunston, Stanley M.}, year={2014}, month={Oct}, pages={471–E75} }