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2.
J Eur Acad Dermatol Venereol ; 35(10): 2067-2073, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33896070

RESUMO

BACKGROUND: While clustering of bullous pemphigoid (BP) with neuropsychiatric diseases is well-established, the clinical and immunological profile of BP patients with this comorbidity remains to be decisively determined. OBJECTIVES: To evaluate the burden of neurological and psychiatric comorbidities among patients with BP and to elucidate the clinical, immunological and immunopathological features of patients with BP and comorbid neuropsychiatric conditions. METHODS: We performed a retrospective study encompassing patients diagnosed with BP throughout the years 2009-2020 in a specialized tertiary referral centre. Multivariate logistic regression model was used to identify predictors of neuropsychiatric conditions among patients with BP. RESULTS: The study included 273 patients with BP, of whom 123 (45.1%) presented with comorbid neuropsychiatric disease. Compared to the remaining patients with BP (n = 150), those with pre-existing neuropsychiatric diseases demonstrated older mean [standard deviation (SD)] age [81.7 (9.1) vs. 76.9 (10.1); P < 0.001], female preponderance (65.0% vs. 49.3%; P = 0.009), higher seropositivity rate of anti-BP230 (67.7% vs. 36.5%; P = 0.006) and higher levels of anti-BP180 NC16A IgG [651.3 (1279.6) vs. 370.4 (818.6) U/mL; P = 0.039]. In multivariate analysis, anti-BP230 seropositivity was independently associated with coexistence of BP with neuropsychiatric conditions [adjusted odds ratio (OR), 3.43; 95% CI, 1.24-9.52; P = 0.018]. In a sensitivity analysis confined to patients with neurological diseases (n = 103), older age [82.1 (8.4) vs. 77.2 (10.3); P < 0.001] and increased anti-BP230 seropositivity (68.0% vs. 39.7%; P = 0.018) were identified. CONCLUSIONS: The coexistence of BP with neuropsychiatric diseases is independently associated with the generation of anti-BP230 antibodies.


Assuntos
Penfigoide Bolhoso , Idoso , Autoanticorpos , Autoantígenos , Comorbidade , Distonina , Feminino , Humanos , Colágenos não Fibrilares , Penfigoide Bolhoso/complicações , Penfigoide Bolhoso/epidemiologia , Estudos Retrospectivos
3.
Arch Dermatol Res ; 313(3): 181-192, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32572565

RESUMO

Impaired cutaneous wound healing remains a major healthcare challenge. The enormity of this challenge is compounded by the lack of preclinical human skin wound healing models that recapitulate selected key factors underlying impaired healing, namely hypoxia/poor tissue perfusion, oxidative damage, defective innervation, and hyperglycaemia. Since organ-cultured human skin already represents a denervated and impaired perfusion state, we sought to further mimic "pathological" wound healing conditions by culturing experimentally wounded, healthy full-thickness frontotemporal skin from three healthy female subjects for three days in either serum-free supplemented Williams' E medium or in unsupplemented medium under "pathological" conditions (i.e. hypoxia [5% O2], oxidative damage [10 mM H2O2], absence of insulin, excess glucose). Under these "pathological" conditions, dermal-epidermal split formation and dyskeratosis were prominent in organ-cultured human skin, and epidermal reepithelialisation was significantly impaired (p < 0.001), associated with reduced keratinocyte proliferation (p < 0.001), cytokeratin 6 expression (p < 0.001) and increased apoptosis (p < 0.001). Moreover, markers of intracutaneous angiogenesis (CD31 immunoreactivity and the number of of CD31 positive cells and CD31 positive vessel lumina) were significantly reduced. Since we had previously shown that thyroxine promotes wound healing in healthy human skin ex vivo, we tested whether this in principle also occurs under "pathological" wound healing conditions. Indeed, thyroxine administration sufficed to rescue re-epithelialisation (p < 0.001) and promoted both epidermal keratinocyte proliferation (p < 0.01) and angiogenesis in terms of CD31 immunoreactivity and CD31 positive cells under "pathological" conditions (p < 0.001) ex vivo. This demonstrates the utility of this pragmatic short-term ex vivo model, which recapitulates some key parameters of impaired human skin wound healing, for the preclinical identification of promising wound healing promoters.


Assuntos
Neovascularização Fisiológica/efeitos dos fármacos , Reepitelização/efeitos dos fármacos , Pele/efeitos dos fármacos , Tiroxina/farmacologia , Idoso , Proliferação de Células/efeitos dos fármacos , Meios de Cultura/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Testa , Humanos , Peróxido de Hidrogênio/metabolismo , Queratinócitos/efeitos dos fármacos , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Estudo de Prova de Conceito , Pele/irrigação sanguínea , Pele/citologia , Técnicas de Cultura de Tecidos/métodos
5.
Br J Dermatol ; 180(5): 1099-1106, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30315657

RESUMO

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering skin disease. Two antigens have been identified as targets of circulating autoantibodies (autoAbs) - BP180 and BP230 - with BP180 being a critical transmembrane adhesion protein of basal keratinocytes of the epidermis. The noncollagenous domain 16A (NC16A) of BP180 is the immunodominant epitope in patients with BP, and anti-BP180-NC16A IgG antibodies (Abs) correlate to disease activity. Routine serological testing and follow-up of BP relies on indirect immunofluorescence (IIF) of serum Abs, commonly performed on monkey oesophagus (ME), and/or enzyme-linked immunosorbent assay (ELISA) testing on recombinantly produced fragments of BP180 and BP230 (BP180-NC16A, BP230-C/N). OBJECTIVES: To determine if NC16A epitopes are well represented on ME substrate. METHODS: Sera from different BP cohorts were tested by IIF on ME and normal human skin (NHS). To confirm findings, affinity-purified anti-BP180-NC16A/BP230 polyclonal Abs and recombinant anti-BP180-NC16A/BP230 monoclonal antibodies (mAbs) were used. RESULTS: For sensitive detection of BP180-NC16A-specific IgG Abs, sections of NHS are superior to the widely used ME. Confirmation comes from polyclonal affinity-purified anti-BP180-NC16A/BP230 Abs, and by mAbs cloned from a patient with active BP. CONCLUSIONS: Use of NHS is preferable over ME in routine IIF testing for BP. These results are of clinical relevance because anti-BP180-NC16A IgG titres are correlated to disease activity and detecting them reliably is important for screening, diagnosis and follow-up of patients with BP.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Esôfago/imunologia , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/diagnóstico , Pele/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Autoanticorpos/imunologia , Autoanticorpos/isolamento & purificação , Epitopos/imunologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo/métodos , Haplorrinos , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina G/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Penfigoide Bolhoso/sangue , Penfigoide Bolhoso/imunologia , Domínios Proteicos/imunologia , Colágeno Tipo XVII
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