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We report a de novo case of severe anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, following the mRNA vaccine for COVID-19, diagnosed on February 2022 in a Nephrology Unit of Southern Italy. The patient was a very young man (21-years-old) of Moroccan origin, who entered the hospital two times, a few days after the first and after the second administration of the BNT162b2 vaccine with fever, respiratory distress and papulo-erythematous/purpuric lesions on limbs and trunk. The laboratory tests revealed: hypereosinophilia, increased creatinine, proteinuria, microhaematuria, increased levels of total IgE and a strong positivity to autoantibodies anti-myeloperoxidase (anti- MPO). Instrumental and biopsc examinations confirmed the diagnostic suspicion. An appropriate laboratory approach, together with clinical surveillance for vaccine immunological complications, should always be performed to help the diagnosis, the monitoring and the clarification of possible vaccine adverse effects. [ABSTRACT FROM AUTHOR]

Objectives To study the phenotype of macrophage infiltrates and their role in angiogenesis in different idiopathic inflammatory myopathies (IIMs). Methods The density and distribution of the subpopulations of macrophages subsets (M1, inducible nitric oxide+, CD11c+; M2, arginase-1+), endomysial capillaries (CD31+, FLK1+), degenerating (C5b-9+) and regenerating (NCAM+) myofibres were investigated by immunohistochemistry in human muscle samples of diagnostic biopsies from a large cohort of untreated patients (n : 81) suffering from anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR)+ immune mediated necrotizing myopathy (IMNM), anti-signal recognition particle (anti-SRP)+ IMNM, seronegative IMNM, DM, PM, PM with mitochondrial pathology, sporadic IBM, scleromyositis, and anti-synthetase syndrome. The samples were compared with mitochondrial myopathy and control muscle samples. Results Compared with the other IIMs and controls, endomysial capillary density (CD) was higher in anti-HMGCR+ IMNM, where M1 and M2 macrophages, detected by confocal microscopy, infiltrated perivascular endomysium and expressed angiogenic molecules such as VEGF-A and CXCL12. These angiogenic macrophages were preferentially associated with CD31+ FLK1+ microvessels in anti-HMGCR+ IMNM. The VEGF-A+ M2 macrophage density was significantly correlated with CD (rS: 0.98; P : 0.0004). Western blot analyses revealed increased expression levels of VEGF-A, FLK1, HIF-1α and CXCL12 in anti-HMGCR+ IMNM. CD and expression levels of these angiogenic molecules were not increased in anti-SRP+ and seronegative IMNM, offering additional, useful information for differential diagnosis among these IIM subtypes. Conclusion Our findings suggest that in IIMs, infiltrating macrophages and microvascular cells interactions play a pivotal role in coordinating myogenesis and angiogenesis. This reciprocal crosstalk seems to distinguish anti-HMGCR associated IMNM. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to test the efficacy of autoantibodies to desmoglein 1 and desmoglein 3 detected by ELISA and indirect immunofluorescence in the diagnosis of oral pemphigus and to correlate the antibody titres with the severity of the disease. Materials and Methods: We report a retrospective cohort study of 22 patients with oral pemphigus and 64 controls from a single tertiary centre. Data about histopathological examination, direct immunofluorescence, indirect immunofluorescence and ELISA were analysed. Global validation of ELISA and IIF both alone and combined was established by calculating sensitivity, specificity, accuracy and both positive predictive value and negative predictive value. The relationship between Oral Disease Severity Score values and ELISA titres was analysed using Pearson's coefficient. Results: The best diagnostic performance was observed for anti‐desmoglein 3 ELISA. The sensitivity was 75% and specificity 100% and positive predictive value and negative predictive value were 92.5% and accuracy 93.9%. The level of agreement with histopathology + direct immunofluorescence was substantial (k =.758). Anti‐desmoglein 3 titres showed a significant correlation with Oral Disease Severity Score (p <.05). Conclusions: Serological tests are commonly employed during clinical practice as adjunctive tools. Anti‐desmoglein 3 ELISA should be considered as a first‐instance diagnostic test for oral pemphigus early detection. [ABSTRACT FROM AUTHOR]

Although, the association between celiac disease (CD) and selective immunoglobulin A deficiency (SIgAD) has been known for more than fifty years, the procedures for diagnosing and monitoring patients with both conditions are still far from definitive. When serological markers were introduced as pre-bioptic investigations, it was immediately clear that searching for specific IgA antibodies without checking total serum IgA could lead to a failure in diagnosing IgA-deficient CD patients, while specific IgG antibodies could be useful as additional tests, because they are frequently found in the serum of affected patients. Nonetheless, until recently the diagnosis of CD in IgA-deficient patients was based on the few, fragmentary and often contradictory data available in literature. The introduction of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines in 2012 provided the current criteria for diagnosing CD in IgA-deficient patients, although some issues remained open, such as the selection of patients who should undergo specific IgG antibody testing and the choice of the most reliable IgG-based test for both diagnosis and follow-up. A real-life study recently assessed the impact of the 2012 ESPGHAN guidelines in diagnosing and monitoring CD in SIgAD patients, highlighting several pitfalls that can lead to operational uncertainties and difficulties in patient management. In the present report, the evolution of diagnostic tools and criteria for CD in SIgAD patients has been critically assessed, both strengths and open issues have been highlighted, and future perspectives for improving the current diagnostic protocols have been suggested. [ABSTRACT FROM AUTHOR]

Objective The aim of our study was to investigate clinical and histopathological findings in adult DM patients positive for anti-Mi2 (anti-Mi2+) antibodies compared with DM patients negative for anti-Mi2 (anti-Mi2–). Methods Clinical data of adult DM patients, who fulfilled EULAR/ACR 2017 classification criteria, were gathered from electronic medical records of three tertiary Rheumatology Units. Histopathological study was carried out on 12 anti-Mi2+ and 14 anti-Mi2– muscle biopsies performed for diagnostic purpose. Nine biopsies from immune mediated necrotizing myopathy (IMNM) patients were used as control group. Results Twenty-two anti-Mi2+ DM [90.9% female, mean age 56.5 (15.7) years] were compared with 69 anti-Mi2– DM patients [71% female, mean age 52.4 (17) years]. Anti-Mi2+ patients presented higher levels of serum muscle enzymes than anti-Mi2– patients [median (IQR) creatine-kinase fold increment: 16 (7–37) vs 3.5 (1–9.9), P  <0.001] before treatment initiation. Moreover, a trend towards less pulmonary involvement was detected in anti-Mi2+ DM (9.1% vs 30.4%, P  =0.05), without any case of rapidly progressive interstitial lung disease. At muscle histology, anti-Mi2+ patients showed more necrotic/degenerative fibres than anti-Mi2– patients [mean 5.3% (5) vs 0.8% (1), P  <0.01], but similar to IMNM [5.9% (6), P  >0.05]. In addition, the endomysial macrophage score was similar between anti-Mi2+ and IMNM patients [mean 1.2 (0.9) vs 1.3 (0.5), P  >0.05], whereas lower macrophage infiltration was found in anti-Mi2– DM [mean 0.4 (0.5), <0.01]. Conclusions Anti-Mi2+ patients represent a specific DM subset with high muscle damage. Histological hallmarks were a higher prevalence of myofiber necrosis, endomysial involvement and macrophage infiltrates at muscle biopsy. [ABSTRACT FROM AUTHOR]

Objective: Aims of this study were to test the efficacy of anti‐BP180‐NC160 ELISA in the diagnosis of oral pemphigoid compared to the gold standard, represented by direct immunofluorescence and pathological examination, to correlate the antibody titers with the severity of the disease and the demographical data. Materials and Methods: Patients with a suspect of oral pemphigoid were enrolled and underwent biopsy and sera collection both, in order to perform histopathological examination, direct immunofluorescence and ELISA. The test outcomes were compared, and ELISA sensitivity, specificity, accuracy, and negative and positive predictive values were calculated. Results: ELISA showed good specificity (83.3%), while sensitivity was only 50%. A moderate correlation between antibody titers and disease severity was recorded. Conclusions: Mucomembranous Pemphigoid is an autoimmune autoantibody‐mediated blistering disease, often affecting exclusively the oral mucosa. Currently, the biopsy is required to diagnose this disease, but serological tests are also commonly employed during clinical practice as adjunctive tools. BP180‐NC160 ELISA should be considered an ancillary diagnostic test in course of oral pemphigoid; direct immunofluorescence + histologic examination remains the diagnostic gold standard. [ABSTRACT FROM AUTHOR]