RESUMEN
In this study, we aimed to examine the relationship between the serum cytokine levels of patients with pemphigus vulgaris (PV) and the Pemphigus Disease Area Index (PDAI), along with the presence of anti-desmoglein (Dsg) 1 antibody, anti-Dsg3 antibody and co-infection among patients with pemphigus vulgaris. This retrospective study included 62 PV patients and 59 healthy individuals who attended the Second Affiliated Hospital of Kunming Medical University from November 2014 to November 2022. The serum concentrations of cytokines and chemokines were assessed using the Luminex 200 System (a high-throughput cytokine detection method). Additionally, anti-Dsg1 and anti-Dsg3 antibodies were determined through enzyme-linked immunosorbent assay, while disease severity was evaluated using the PDAI scoring system. The PV group exhibited elevated levels of Th1 cytokines (such as interleukin (IL)-1RA, IL-1ß, IL-2, IL-12p70, GM-CSF, TNF-α, IL-18, IFN-γ), Th2 cytokines (IL-5, IL-10, IL-13) and Th17/Th22-related cytokines (IL-17A, IL-22) compared to the healthy control group (p < 0.05). Conversely, the levels of chemokines (macrophage inflammatory protein-1 alpha (MIP-1α), stromal cell-derived factor-1 alpha (SDF-1α), interferon-inducible protein-10 (IP-10), Regulated on Activation in Normal T-Cell Expressed And Secreted (RANTES), growth-regulated on-gene-alpha (GRO-α), MIP-1ß) and Th2 (IL-31) were lower in the PV group compared to the healthy control group (p < 0.05). No significant differences were observed in other cytokines and chemokines (p > 0.05). Additionally, IL-7, IFN-γ, IL-18 and GRO-α showed positive correlations with PDAI, IL-6 correlated positively with anti-Dsg3 antibody levels, and IL-12p70, IL-18, and IFN-γ correlated positively with anti-Dsg1 antibody levels. Furthermore, IL-15 exhibited a positive association with skin infections. PV patients have elevated levels of various cytokines and chemokines, and there are different degrees of elevation in cytokines and chemokines associated with the activation of various T cell subsets. PDAI and the Dsg1 antibody levels are mainly related to the Th1-related cytokines.
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Quimiocinas , Citocinas , Desmogleína 1 , Pénfigo , Humanos , Pénfigo/sangre , Pénfigo/inmunología , Estudios Retrospectivos , Masculino , Femenino , Citocinas/sangre , Persona de Mediana Edad , Adulto , Desmogleína 1/inmunología , Quimiocinas/sangre , Desmogleína 3/inmunología , Índice de Severidad de la Enfermedad , Anciano , Autoanticuerpos/sangre , Estudios de Casos y Controles , Relevancia ClínicaRESUMEN
Cell-cell junctions, and specifically desmosomes, are crucial for robust intercellular adhesion. Desmosomal function is compromised in the autoimmune blistering skin disease pemphigus vulgaris. We combine whole-genome knockout screening and a promotor screen of the desmosomal gene desmoglein 3 in human keratinocytes to identify novel regulators of intercellular adhesion. Kruppel-like-factor 5 (KLF5) directly binds to the desmoglein 3 regulatory region and promotes adhesion. Reduced levels of KLF5 in patient tissue indicate a role in pemphigus vulgaris. Autoantibody fractions from patients impair intercellular adhesion and reduce KLF5 levels in in vitro and in vivo disease models. These effects were dependent on increased activity of histone deacetylase 3, leading to transcriptional repression of KLF5. Inhibiting histone deacetylase 3 increases KLF5 levels and protects against the deleterious effects of autoantibodies in murine and human pemphigus vulgaris models. Together, KLF5 and histone deacetylase 3 are regulators of desmoglein 3 gene expression and intercellular adhesion and represent potential therapeutic targets in pemphigus vulgaris.
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Adhesión Celular , Desmogleína 3 , Queratinocitos , Factores de Transcripción de Tipo Kruppel , Pénfigo , Humanos , Pénfigo/metabolismo , Pénfigo/patología , Pénfigo/inmunología , Desmogleína 3/metabolismo , Desmogleína 3/genética , Animales , Queratinocitos/metabolismo , Ratones , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Autoanticuerpos/inmunología , Desmosomas/metabolismo , Modelos Animales de Enfermedad , Histona Desacetilasas/metabolismo , Histona Desacetilasas/genética , Regulación de la Expresión Génica , Regiones Promotoras Genéticas/genética , MasculinoRESUMEN
Pemphigus is an autoimmune disease that affects the skin and mucous membranes, induced by the deposition of pemphigus IgG, which mainly targets desmogleins 1 and 3 (Dsg1 and 3). This autoantibody causes steric interference between Dsg1 and 3 and the loss of cell adhesion, producing acantholysis. This molecule and its cellular effects are clinically reflected as intraepidermal blistering. Pemphigus vulgaris-IgG (PV-IgG) binding involves p38MAPK-signaling-dependent caspase-3 activation. The present work assessed the in vitro effect of PV-IgG on the adherence of HaCaT cells dependent on caspase-3. PV-IgG induced cell detachment and apoptotic changes, as demonstrated by annexin fluorescent assays. The effect of caspase-3 induced by PV-IgG was suppressed in cells pre-treated with caspase-3-shRNA, and normal IgG (N-IgG) as a control had no relevant effects on the aforementioned parameters. The results demonstrated that shRNA reduces caspase-3 expression, as measured via qRT-PCR and via Western blot and immunofluorescence, and increases cell adhesion. In conclusion, shRNA prevented in vitro cell detachment and the late effects of apoptosis induced by PV-IgG on HaCaT cells, furthering our understanding of the molecular role of caspase-3 cell adhesion dependence in pemphigus disease.
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Apoptosis , Autoanticuerpos , Caspasa 3 , Adhesión Celular , Pénfigo , ARN Interferente Pequeño , Humanos , Pénfigo/inmunología , Pénfigo/patología , Caspasa 3/metabolismo , Autoanticuerpos/inmunología , ARN Interferente Pequeño/genética , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , Línea Celular , Células HaCaT , Desmogleína 3/inmunología , Desmogleína 3/metabolismo , Desmogleína 3/genética , Queratinocitos/metabolismoRESUMEN
Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase, plays a remarkable role in the transmission and amplification of extracellular signals to intracellular signaling pathways. Various types of cells use the BTK pathway to communicate, including hematopoietic cells particularly B cells and T cells. The BTK pathway plays a role in controlling the proliferation, survival, and functions of B cells as well as other myeloid cells. First, second, and third-generation BTK inhibitors are currently being evaluated for the treatment of immune-mediated diseases in addition to B cell malignancies. In this article, the available evidence on the action mechanisms of BTK inhibitors is reviewed. Then, the most recent data obtained from preclinical studies and ongoing clinical trials for the treatment of autoimmune diseases, such as pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, systemic lupus erythematosus, Sjögren's disease, rheumatoid arthritis, systemic sclerosis, multiple sclerosis, myasthenia gravis, and inflammatory diseases such as psoriasis, chronic spontaneous urticaria, atopic dermatitis, and asthma are discussed. In addition, adverse effects and complications associated with BTK inhibitors as well as factors predisposing patients to BTK inhibitors complications are discussed.
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Agammaglobulinemia Tirosina Quinasa , Enfermedades Autoinmunes , Pénfigo , Inhibidores de Proteínas Quinasas , Transducción de Señal , Humanos , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Enfermedades Autoinmunes/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pénfigo/tratamiento farmacológico , Pénfigo/inmunología , Pirimidinas/uso terapéutico , Piperidinas/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Miastenia Gravis/tratamiento farmacológico , Esclerosis Múltiple/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirazoles/farmacología , Nitrilos/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Adenina/análogos & derivados , Adenina/uso terapéutico , Asma/tratamiento farmacológico , Linfocitos B/inmunología , Síndrome de Sjögren/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Esclerodermia Sistémica/tratamiento farmacológico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Benzamidas , Imidazoles , PirazinasRESUMEN
Antibody-mediated receptor activation is successfully used to develop medical treatments. If the activation induces a pathological response, such antibodies are also excellent tools for defining molecular mechanisms of target receptor malfunction and designing rescue therapies. Prominent examples are naturally occurring autoantibodies inducing the severe blistering disease pemphigus vulgaris (PV). In the great majority of patients, the antibodies bind to the adhesion receptor desmoglein 3 (Dsg3) and interfere with cell signaling to provoke severe blistering in the mucous membranes and/or skin. The identification of a comprehensive causative signaling network downstream of antibody-targeted Dsg3 receptors (e.g., shown by pharmacological activators or inhibitors) is currently being discussed as a basis to develop urgently needed first-line treatments for PV patients. Although polyclonal PV IgG antibodies have been used as proof of principle for pathological signal activation, monospecific anti-Dsg3 antibodies are necessary and have been developed to identify pathological Dsg3 receptor-mediated signal transduction. The experimental monospecific PV antibody AK23, produced from hybridoma cells, was extensively tested in our laboratory in both in vitro and in vivo models for PV and proved to recapitulate the clinicopathological features of PV when generated using the standardized production and purification protocols described herein. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Bovine IgG stripping from FBS and quality control Basic Protocol 2: AK23 hybridoma expansion and IgG production Basic Protocol 3: AK23 IgG purification Basic Protocol 4: AK23 IgG quality control Support Protocol 1: Detection of endotoxin levels Support Protocol 2: Detection and removal of mycoplasma.
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Desmogleína 3 , Pénfigo , Pénfigo/inmunología , Pénfigo/patología , Desmogleína 3/inmunología , Animales , Humanos , Ratones , Autoanticuerpos/inmunología , Investigación Biomédica TraslacionalRESUMEN
Several auto-immune diseases have been linked to vitamin D deficiency as a contributing environmental factor. Its pleiotropic effects on the immune system, especially its essential role in maintaining immune tolerance, make the vitamin D pathway of great interest. In this study, we focused on Pemphigus foliaceous (PF) in Tunisian population. we aimed to quantify the Serum 25[OH]D levels using chemiluminescence assay and to analyze the differential expression of the VDR, CYP27B1 and CYP24A1 genes in the circulating blood cells and lesional skin tissue of PF patients using Q-PCR. A genetic explanation was then sought to explore any direct relationship between tag polymorphisms and the inherited features of PF. Results confirmed a vitamin D hypovitaminosis in Tunisian PF patients. Interestingly, a differential gene expression correlated to the disease stratification was noted. Indeed, at the systemic level, an upregulation of VDR and CYP27B1 genes was observed in healthy controls compared to PF patients. Notably, in lesional skin tissue, the clinical and serological remission phase was correlated with high transcriptional levels of the VDR gene and conversely a drop in expression of the CYP24A1 gene. Genetic analysis indicated the involvement of the most appealing polymorphisms, rs2228570 and poly (A) microsatellite, in PF etiopathogenesis. Indeed, CAC13 haplotype was associated with a higher risk of PF development. Our findings suggest that alterations in the vitamin D-VDR pathway may influence PF physiopathology, making this pathway a potential target for pharmacological modulation, especially for cortico-resistant PF patients.
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25-Hidroxivitamina D3 1-alfa-Hidroxilasa , Pénfigo , Receptores de Calcitriol , Deficiencia de Vitamina D , Vitamina D3 24-Hidroxilasa , Vitamina D , Humanos , Pénfigo/inmunología , Pénfigo/genética , Pénfigo/diagnóstico , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Vitamina D3 24-Hidroxilasa/genética , Vitamina D3 24-Hidroxilasa/metabolismo , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/metabolismo , Vitamina D/metabolismo , Vitamina D/sangre , Vitamina D/análogos & derivados , Femenino , Masculino , Persona de Mediana Edad , Adulto , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/inmunología , Deficiencia de Vitamina D/sangre , Túnez , Anciano , Polimorfismo de Nucleótido Simple , Piel/patología , Piel/inmunología , Piel/metabolismo , Predisposición Genética a la Enfermedad , Estudios de Casos y ControlesRESUMEN
Pemphigus vulgaris (PV) is a rare autoimmune disorder where autoantibodies target the desmosomal proteins resulting in blistering of oral mucosa and skin. While the pathogenesis of PV is mainly mediated by the adaptive immune system, key players of innate immunity are also emerging. This study outlines the phenotypic as well as functional attributes of NK cells in PV. Through in-depth analysis using flow cytometry we identified an increase in the frequency of CD56+ CD3- NK cells and their subtypes in periphery. Along with this there is an increased frequency of IFNγ+ CD56bright CD16dim NK cells. mRNA expression of sorted NK cells for differentially expressed genes, particularly key transcription factors such as T-bet and EOMES, as well as surface receptors like NKG2D and KIR2D, and the cytokine IFNγ, displayed significant upregulation. A significant activation of NK cells was seen in the disease state. The levels of perforin and IFNγ were significantly elevated in the culture supernatants of patients. Additionally, a significantly higher cytotoxicity of NK cells in PV was observed. In lesioned tissues of PV, NK related markers were significantly increased. Lastly, we observed NK cells using confocal microscopy in the tissue biopsies of patients which showed significant infiltration of CD56+ CD3- NK cells at the lesional sites. This study aimed to shed light on the pivotal role of NK cells in the immunopathology of PV, offering a thorough understanding of their behaviour and changes in expression which might help in contributing to the development of novel therapeutics.
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Células Asesinas Naturales , Pénfigo , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Pénfigo/inmunología , Pénfigo/terapia , Pénfigo/metabolismo , Femenino , Masculino , Interferón gamma/metabolismo , Persona de Mediana Edad , Adulto , Perforina/metabolismo , Inmunofenotipificación , Citotoxicidad Inmunológica , Activación de Linfocitos/inmunología , Anciano , Recuento de LinfocitosRESUMEN
Keratinocytes in mucosal and skin tissues maintain tissue integrity via desmosomes and desmoglein-3 (Dsg3). Pemphigus Vulgaris (PV) is a life-threatening autoimmune blistering disease characterized by autoantibodies against Dsg3, disrupting desmosomes. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates oxidative stress responses crucial for skin tissue protection. Although the pathogenesis of PV is known, the detailed molecular events remain unclear. This study investigates changes in Nrf2 expression in keratinocytes following pathogenic anti-Dsg3 antibody AK23 exposure, using dose- and time-dependent studies employing immunofluorescence analysis. N/TERT keratinocytes were cultured in keratinocytes serum-free medium and treated with AK23 at varying doses (5 µg/mL,40µg/mL,75µg/mL) and durations (2, 6, 24 h). Immunofluorescence staining was performed to assess the expression of Nrf2 and Dsg3. All fluorescent images were analyzed using ImageJ software. A dose-dependent increase in Dsg3 was noted following AK23 treatment, while Nrf2 expression and subcellular localization varied. Time-course analyses showed decreased Nrf2 at 24 h and increased Dsg3 levels. Early time-point (2 and 6 h) variations were evident in Nrf2 levels. This study highlights the impact of AK23 on Nrf2 expression, potentially disrupting Nrf2-mediated cytoprotection and implicating oxidative stress (ROS generation) in PV pathogenesis. Further investigation is necessary to validate the findings.
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Desmogleína 3 , Queratinocitos , Factor 2 Relacionado con NF-E2 , Pénfigo , Especies Reactivas de Oxígeno , Pénfigo/inmunología , Pénfigo/metabolismo , Pénfigo/patología , Factor 2 Relacionado con NF-E2/metabolismo , Queratinocitos/metabolismo , Queratinocitos/inmunología , Desmogleína 3/inmunología , Desmogleína 3/metabolismo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo , Anticuerpos Monoclonales/farmacología , Línea Celular , Autoanticuerpos/inmunologíaRESUMEN
BACKGROUND: The meticulous selection of appropriate vaccine adjuvants is crucial for optimizing immune responses. Traditionally, pemphigus vulgaris (PV), an autoimmune disorder, has been modelled using complete Freund's adjuvant (CFA). In this study, we aimed to discern potential variations in immune responses elicited by Toll-like receptor (TLR) ligands as compared to CFA. METHODS: A comprehensive investigation was conducted, comparing the effects of these adjuvants in conjunction with ovalbumin or desmoglein-3. Flow cytometry was employed to analyse distinct cell subsets, while enzyme-linked immunosorbent assay quantified antigen-specific antibodies and cytokine levels. Histological examination of harvested skin tissues and transcriptome analysis of skin lesions were performed to identify differentially expressed genes. RESULTS: TLR ligands demonstrated efficacy in inducing PV-like symptoms in wild-type mice, in contrast to CFA. This underscored the substantial impact of the adjuvant on self-antigen tolerance. Furthermore, we proposed an enhanced method for establishing a PV model through adoptive transfer, substituting CFA with TLR ligands. Our results revealed that in contrast to the perception that CFA being the most potent immunopotentiator reported, CFA promoted regulatory T cells (Treg), follicular regulatory T cells and IL-10-producing neutrophils, whereas TLR ligands downregulated CCL17 and IL-10. This suggested potential implications for the recruitment and activation of Treg subsets. While B cell and CD8+ T cell responses exhibited similarity, CFA induced less activation in dendritic cell subsets. A novel mouse model of PV and systemic comparison of immunostimulatory effects of adjuvants were provided by this study. CONCLUSIONS: The systematic comparison of CFA and TLR ligands shed light on the distinctive properties of these adjuvants, presenting innovative mouse models for the investigation of pemphigus. This study significantly contributes to adjuvant research and advances our understanding of PV pathogenesis. KEY POINTS/HIGHLIGHTS: Immunization with desmoglein 3 and Toll-like receptor (TLR) ligands effectively induces pemphigus symptoms in wild-type mice, whereas complete Freund's adjuvant (CFA) fails. TLR ligands heightened the autoreactivity of donor cells in the adoptive transfer pemphigus model. CFA promoted regulatory T cells and IL-10-producing neutrophils, whereas TLR ligands downregulated CCL17 and IL-10, leading to more effective immune responses.
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Adyuvantes Inmunológicos , Modelos Animales de Enfermedad , Pénfigo , Receptores Toll-Like , Animales , Pénfigo/inmunología , Ratones , Receptores Toll-Like/metabolismo , Receptores Toll-Like/inmunología , Receptores Toll-Like/agonistas , Adyuvantes Inmunológicos/farmacología , Adyuvante de Freund/inmunología , Ratones Endogámicos C57BL , Ligandos , Ovalbúmina/inmunología , FemeninoRESUMEN
BACKGROUND: Pemphigus is a group of potentially life-threatening autoimmune bullous diseases induced by pathogenic autoantibodies binding to the surface of epidermal cells. The role of the gut microbiota (GM) has been described in various autoimmune diseases. However, the impact of the GM on pemphigus is less understood. This study aimed to investigate whether there was alterations in the composition and function of the GM in pemphigus patients compared to healthy controls (HCs). METHODS: Fecal samples were collected from 20 patients with active pemphigus (AP), 11 patients with remission pemphigus (PR), and 47 HCs. To sequence the fecal samples, 16S rRNA was applied, and bioinformatic analyses were performed. RESULTS: We found differences in the abundance of certain bacterial taxa among the three groups. At the family level, the abundance of Prevotellaceae and Coriobacteriaceae positively correlated with pathogenic autoantibodies. At the genus level, the abundance of Klebsiella, Akkermansia, Bifidobacterium, Collinsella, Gemmiger, and Prevotella positively correlated with pathogenic autoantibodies. Meanwhile, the abundance of Veillonella and Clostridium_XlVa negatively correlated with pathogenic autoantibodies. A BugBase analysis revealed that the sum of potentially pathogenic bacteria was elevated in the AP group in comparison to the PR group. Additionally, the proportion of Gram-negative bacteria in the PR group was statistically significantly lower in comparison to the HC group. CONCLUSION: The differences in GM composition among the three groups, and the correlation between certain bacterial taxa and pathogenic autoantibodies of pemphigus, support a linkage between the GM and pemphigus.
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Autoanticuerpos , Disbiosis , Heces , Microbioma Gastrointestinal , Pénfigo , Humanos , Pénfigo/inmunología , Pénfigo/microbiología , Microbioma Gastrointestinal/inmunología , Autoanticuerpos/inmunología , Masculino , Femenino , Disbiosis/inmunología , Disbiosis/microbiología , Persona de Mediana Edad , Adulto , Heces/microbiología , ARN Ribosómico 16S/genética , Anciano , Estudios de Casos y Controles , Bacterias/inmunología , Bacterias/clasificaciónAsunto(s)
Interleucinas , Pénfigo , Pénfigo/sangre , Pénfigo/inmunología , Humanos , Interleucinas/sangre , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios de Casos y Controles , AncianoAsunto(s)
Autoanticuerpos , Autoantígenos , Colágeno Tipo XVII , Desmocolinas , Colágenos no Fibrilares , Pénfigo , Humanos , Pénfigo/inmunología , Pénfigo/patología , Desmocolinas/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Colágenos no Fibrilares/inmunología , Autoantígenos/inmunología , Femenino , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Anti-desmoglein (Dsg)1 is produced in pemphigus foliaceus (PF), affecting exclusively the skin. Pemphigus vulgaris (PV) shows the production of anti-Dsg3 in the mucosal form, and anti-Dsg1 and 3 in the mucocutaneous form. Anti-Dsg3 autoantibodies have been rarely reported in PF. OBJECTIVES: To determine the factors associated with the production and pathogenicity of anti-Dsg3 in PF. METHODS: Comparative analytical study of three patients groups: 16 PF-anti-Dsg3+, and 42 PF-anti-Dsg3(-) and 22 PV treatment-naïve cases. Serum was used in the anti-Dsg1 and 3 ELISA, and in immunoblotting (IB) with human epidermis extract. The expression of Dsg1 and 3 in paraffin sections was analyzed by immunohistochemistry (IHC). HLA-DRB1 alleles were compiled from a database. RESULTS: In the PF-anti-Dsg3+ group: age range similar to that of the PV group (pâ¯>â¯0.9999); predominance of the generalized form of PF (pâ¯=â¯0.002); anti-Dsg3 titers lower than those of PV (pâ¯<â¯0.0001); IB confirmed Dsg3 identification in one (8.33%) of 12 patients; IHC showed exclusive cytoplasmic internalization of Dsg1; HLA-DRB1 alleles of susceptibility to PF, with the absence of alleles associated with PV, in the five typed patients. STUDY LIMITATIONS: Most of the patients in the PF-anti-Dsg3+ group were undergoing treatment. CONCLUSION: The presence of anti-Dsg3 antibodies in PF was related to older age (comparable to that of PV) and the generalized form of PF. The non-pathogenicity of anti-Dsg3 antibodies in PF can be attributed to the low serum anti-Dsg3 titers, the lack of Dsg3 internalization as detected by IHC, and the absence of PV-associated HLA-DRB1 alleles.
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Autoanticuerpos , Desmogleína 1 , Desmogleína 3 , Inmunohistoquímica , Pénfigo , Humanos , Pénfigo/inmunología , Desmogleína 3/inmunología , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Desmogleína 1/inmunología , Ensayo de Inmunoadsorción Enzimática , Adulto Joven , Immunoblotting , Cadenas HLA-DRB1/genética , Cadenas HLA-DRB1/inmunología , Anciano de 80 o más Años , AdolescenteRESUMEN
Rituximab is a monoclonal antibody that targets CD20 antigen in B cells. For pemphigus, rituximab has been highly effective in steroid-sparing therapy for moderate to severe cases. Originator rituximab has demonstrated favorable treatment effects in patients with pemphigus, but its high cost remains a challenge. Biosimilar rituximab is expected to offer a potential solution. However, it is required for the comparative study of efficacy and safety between biosimilar and originator because all biosimilars may not be identical to the originator. In this study, we compared the treatment effects and safety of biosimilar (Truxima) and originator (MabThera) rituximab in patients with pemphigus. A final cohort of 52 patients in the MabThera group and 72 patients in the Truxima group was enrolled. Except for the intravenous immunoglobulin administration rate, there were no differences in baseline characteristics between the two groups, and for the purpose of comparing efficacy, investigations into time to complete remission, total steroid intake to complete remission, and total steroid intake for 6 months following rituximab treatment revealed no significant differences between the two groups. Truxima can be considered a relatively affordable alternative treatment option for pemphigus, offering cost-effectiveness to patients who are indicated for the treatment with MabThera.
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Biosimilares Farmacéuticos , Pénfigo , Rituximab , Humanos , Rituximab/efectos adversos , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Pénfigo/tratamiento farmacológico , Pénfigo/inmunología , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/economía , Masculino , Femenino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Anciano , Factores Inmunológicos/uso terapéutico , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/administración & dosificación , Inducción de Remisión/métodos , Estudios RetrospectivosRESUMEN
Autoimmune dermatopathies are not common in horses. These autoimmune diseases can be idiopathic or triggered by an antigen such as drugs, vaccines, or neoplasia. The most common one is pemphigus foliaceus, which manifests as a pustular, crusting eruption. Other more common pustular diseases should be ruled out before considering pemphigus. Vasculitis is relatively common in horses and can be triggered by a variety of antigenic stimulations. Systemic lupus and true idiopathic autoimmune vasculitis are very rare in horses. Every effort should be made to reach a final diagnosis, as the prognosis for true idiopathic autoimmune skin diseases is poor.
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Enfermedades Autoinmunes , Enfermedades de los Caballos , Enfermedades de la Piel , Caballos , Animales , Enfermedades de los Caballos/diagnóstico , Enfermedades de los Caballos/inmunología , Enfermedades Autoinmunes/veterinaria , Enfermedades Autoinmunes/diagnóstico , Enfermedades de la Piel/veterinaria , Enfermedades de la Piel/diagnóstico , Pénfigo/veterinaria , Pénfigo/diagnóstico , Pénfigo/patología , Pénfigo/inmunologíaAsunto(s)
Autoanticuerpos , Desmogleína 3 , Penfigoide Ampolloso , Pénfigo , Humanos , Pénfigo/inmunología , Pénfigo/diagnóstico , Pénfigo/patología , Desmogleína 3/inmunología , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/patología , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Mucosa Bucal/patología , Mucosa Bucal/inmunología , Femenino , Masculino , AncianoRESUMEN
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.
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Autoanticuerpos , Desmocolinas , Enfermedades de los Perros , Inmunoglobulina A , Pénfigo , Perros , Animales , Pénfigo/inmunología , Pénfigo/veterinaria , Desmocolinas/inmunología , Enfermedades de los Perros/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina A/sangre , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Humanos , Células HEK293 , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre , Técnica del Anticuerpo Fluorescente Indirecta/veterinariaRESUMEN
Pemphigus, a potentially lethal autoimmune skin disease, is mediated by desmoglein-specific antibodies, manifesting cutaneous and mucosal blisters and erosions. The interaction between multiple immune counterparts contributes to the progress of pemphigus. Currently, the emergence of bioinformatic analysis enables investigators to gain a global picture of the pemphigus immune network, based on the exhaustive pedigree annotation of multiple subsets. T helper subsets dominate the landscape as mentioned previously, and innate immune cells have been involved as well. Of particular interests is which phenotype of T cells orchestrates the autoimmune process and chronic inflammation in a certain condition. In this review, the circulatory and peripheral immune cells and cytokine components constituting the immune microenvironment are separately discussed to provide a perspective on pemphigus pathogenesis, with particular reference to insights provided by the bioinformation technique.