1,721,033 research outputs found

    EXTRACELLULAR VESICLES AS VEHICLES OF AUTOANTIGENS IN AUTOIMMUNE BULLOUS DISEASES

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    Background Autoimmune bullous diseases (AIBDs) are organ specific rare autoimmune diseases associated with significantly morbidity and mortality. The most common AIBD is bullous pemphigoid (BP), in which pathogenic autoantibodies target the haemidesmosomal proteins of the dermo-epidermal junction, namely BP180 (collagen 17A) and BP230. Extracellular vesicles (EVs) are small membranous structures, which encapsulate proteins, miRNA, mRNA and lipids, and represent pivotal mediators of intercellular communication. EVs have been demonstrated to carry tissue-specific autoantigens in other autoimmune diseases, such as rheumatoid arthritis and lupus erythematosus, and in transplant organ rejection; this phenomenon was demonstrated to have pathogenic implications in autoimmune diseases and to correlate with transplant rejection severity. Objectives The purpose of this study was to identify the presence targeted autoantigens in EVs derived from the sera and blister fluid of BP patients. Methods We isolated, by size exclusion chromatography, EVs derived from serum and blisters of BP-patients and from serum or suction blisters of healthy donors. EV characterization was performed by flow cytometry analysis and nanoparticle tracking analysis. Flow cytometry analysis was also used to investigated surface expression of skin autoantigen in serum derived EVs. Western blot analysis was used to investigate the presence of autoantigens in blister fluid derived EVs of BP patients and in EVs derived from suction, burn or pressure blisters of healthy controls. Results Flow cytometry analysis confirmed that the retrieved nanoparticle suspension was enriched in EVs and nanoparticle tracking analysis indicated that the EV-enriched fractions were enriched in particles with a size distribution characterizing small-EVs (main peak was present at 94.5nm). BP180 was found, by western blot analysis, in EVs derived from blister fluid of 6 out 11 BP patients and in none of EVs isolated from suction blister fluid of healthy donors. BP230 and Dsg1 were not detectable in EVs of none of samples. No specific clinical characteristics seemed to correlate to the presence of BP180 in EVs. EV-encapsulated autoantigens in BP might represent a direct or indirect route of antigen presentation without cell-to-cell contact; a depletion route of BP180 contributing to the mechanical detachment of keratinocytes during blister formation and a way to spread among adjacent keratinocytes signals of internalization or depletion of BP180; or a prognostic marker of disease severity. Conclusions This is a preliminary study but, the discovery of BP180, the most important autoantigen target in BP, in EVs derived from blister fluid might contribute to the unraveling of BP pathogenesis

    Evaluation of Helicobacter pylori with a stool antigen assay in frail, elderly patients

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    Helicobacter pylori infection has not been studied thoroughly in elderly patients. The aim of this study was to evaluate the reliability of stool antigen assay (HpSA) in the assessment of H. pylori infection in hospitalized, frail, elderly patients. The study population consisted of 85 consecutively recruited elderly patients (> or =65 years old) hospitalized between May 1999 and December 2001 with diagnostic indications for upper gastrointestinal endoscopy. Twenty-nine subjects had been receiving treatment with proton-pump inhibitors (PPIs), such as omeprazole (10-20 mg/day) for 2-15 days, and 56 were not receiving treatment. HpSA was evaluated versus UBT (urea breath test), serology and histology: patients with at least two positive results out of the latter three tests were considered positive for H. pylori infection, while patients with at least two negative tests out of three were considered negative. The sensitivity and specificity of HpSA in the 56 untreated patients were, respectively, 76% (true positives TP = 22; false negatives FN = 7) and 93% (true negatives TN = 25; false positives FP = 2). The sensitivity and specificity of HpSA in the 29 patients on PPI treatment were, respectively, 82% (TP = 9; FN = 2) and 83% (TN = 15; FP = 3). HpSA is an accurate, non-invasive and easy method for diagnosing H. pylori infection in elderly patients

    Infantile bullous pemphigoid

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    Bullous pemphigoid (BP) is relatively rare in the paediatric age group, with slightly more than 100 cases of BP reported in the literature. In this article, we focus on infantile BP (>= 28 days, <12 months), presenting a systematic review of cases of infantile BP in the literature from 1977 up to the present day. Fifty-four articles were selected, regarding 74 patients with infantile BP. All cases presented involvement of the hands and feet, of which 67/74 (91%) showed subsequent generalized involvement and 7/74 (9%) remained localized. Oral mucosal involvement was reported in 9/62 (15%) patients in whom mucous membranes were investigated. Based on ELISA, all patients had antibodies directed against BPAG2 and only a minority also had antibodies against BPAG1 (8%). Mid-to-high-potency topical steroids BID alone should be used only in mild/localized cases with BSA < 10%. Children with generalized disease with BSA> 10% require systemic steroids, mostly prednisolone at a dosage of 1-2 mg/kg/die. Our study yielded a smaller number of cases of infantile BP, compared to previous reviews, due to the fact that diagnosis of BP was often only based on direct immunofluorescence findings and clinical appearance, without further identification of the targeted auto-antigen. Nevertheless, our findings are in accordance with those of the literature and suggest that BP in infants exhibits specific, characteristic epidemiology, clinical presentation and prognosis

    Not all “Candida” are “Candida”: Nakaseomyces glabratus (H.W. Anderson) Sugita & M. Takask. 2022 onychomycosis and the need for rapid diagnostic

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    Onychomycosis is a common nail disorder typically caused by dermatophytes, with Candida species and non-dermatophytic molds being less frequent agents. Nakaseomyces glabratus (formerly Candida glabrata) is a rare cause of nail infections, notable for its intrinsic resistance to azoles and diagnostic challenges. We report a case of chronic nail discoloration, thickening, and fragility initially misdiagnosed as psoriasis. Microscopy and culture, followed by selective medium analysis, confirmed N. glabratus infection. This case emphasizes the importance of considering uncommon yeast species and highlights both the need for accurate identification to guide therapy and the possible misdiagnosis with other pathologies. Awareness and proper diagnostic approaches are essential for timely and effective management of such rare fungal nail infections
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