👤 Salvatore De Vita

The diagnosis of Sjögren's disease (SjD) in patients without autoantibodies against Ro/SSA is a major challenge. We aimed to identify novel autoantibodies in SjD that may facilitate the diagnostic procedure for Ro/SSA negative SjD. IgG and IgA autoantibody reactivity of 94 potential candidate autoantigens for SjD, selected from a discovery screen of 1,629 human antigens coupled to Luminex beads and prior knowledge about potential biological relevance, were examined in serum of SjD patients (n=347) using Luminex and ELISA technology. Healthy (HC, n=118) and non-Sjögren's sicca syndrome (NSS, n=44) individuals served as controls. To assess disease specificity, the novel autoantibodies were also measured in serum of patients with Rheumatoid Arthritis (RA, n=50), Systemic Lupus Erythematosus (SLE, n=49), and Systemic Sclerosis (SSc, n=37). 45 novel autoantibodies were significantly (p ≤ 0.05) more prevalent in SjD than in HC and were detected in up to 19% of the SjD cohort. The most common autoantibodies were against CCL4, M5, TMPO and OAS3. Some of the novel autoantibodies were associated with extraglandular disease manifestations, such as anti-TONSL or anti-IL6 with pulmonary involvement. We have developed a three and five marker panel for the detection of Ro/SSA negative patients, consisting of anti-FNBP4, anti-SNRPC, anti-CCL4, anti-M3 and anti-KDM6B, which had a sensitivity of up to 46% with a specificity of 95% (SjD vs. HC). Both panels discriminate these patients from HC, whereas the three-marker more effectively differentiates between Ro/SSA negative patients and NSS. Novel autoantibodies will facilitate the diagnosis of Ro/SSA negative patients with SjD, in particular our predictive panel will be useful in the diagnosis and differentiation of these patients from healthy and NSS individuals in a clinical context. In addition, the autoantibodies may also be useful for risk stratification of extraglandular manifestations. Show less

Bladder cancer (BC) is the tenth most common cancer, with urothelial carcinoma representing about 90% of all BC, including neoplasms and carcinomas of different grades of malignancy. Urinary cytology has a significant role in BC screening and surveillance, although it has a low detection rate and high dependence on the pathologist's experience. The currently available biomarkers are not implemented into routine clinical practice due to high costs or low sensitivity. In recent years, the role of lncRNAs in BC has emerged, even though it is still poorly explored. We have previously shown that the lncRNAs Metallophosphoesterase Domain-Containing 2 Antisense RNA 1 (MPPED2-AS1), Rhabdomyosarcoma-2 Associated Transcript (RMST), Kelch-like protein 14 antisense (Klhl14AS) and Prader Willi/Angelman region RNA 5 (PAR5) are involved in the progression of different types of cancers. Here, we investigated the expression of these molecules in BC, first by interrogating the GEPIA database and observing a different distribution of expression levels between normal and cancer specimens. We then measured them in a cohort of neoplastic bladder lesions, either benign or malignant, from patients with suspicion of BC undergoing transurethral resection of bladder tumor (TURBT). The total RNA from biopsies was analyzed using qRT-PCR for the expression of the four lncRNA genes, showing differential expression of the investigated lncRNAs between normal tissue, benign lesions and cancers. In conclusion, the data reported here highlight the involvement of novel lncRNAs in BC development, whose altered expression could potentially affect the regulatory circuits in which these molecules are involved. Our study paves the way for testing lncRNA genes as markers for BC diagnosis and/or follow-up. Show less