Multiple sclerosis (MS) is an autoimmune pathology leading to neurodegeneration. Because of the complexity and heterogenic etiology of this disease, diagnosis and treatment for individual patients are challenging. Exosome‐associated microRNAs (miRNAs) have recently emerged as a new class of diagnostic biomarkers involved in both autoimmune and neurologic disorders. Interesting new evidence has emerged showing that circulating miRNAs are dysregulated in MS body fluids, including serum, plasma, and cerebrospinal fluid. We hypothesized that exosome‐associated miRNAs could present a readily accessible blood‐based assay for MS disease. We detected expression of miRNAs by quantitative PCR on a small cohort of MS patients. We analyzed circulating exosome‐associated miRNAs of MS patients before and after therapy and found that 14 exosome‐associated miRNAs were significantly down‐regulated, while 2 exosome‐associated miRNAs were significantly up‐regulated in IFN‐β‐treated relapsing‐remitting MS patients with response to therapy compared to those without response. We identified a serum miRNA panel that could be used to monitor the response to IFN‐β therapy. Overall, these data suggest that circulating exosome‐associated miRNA profiling could represent an easily detectable biomarker of disease and treatment response.—Manna, I., Iaccino, E., Dattilo, V., Barone, S., Vecchio, E., Mimmi, S., Filippelli, E., Demonte, G., Polidoro, S., Granata, A., Scannapieco, S., Quinto, I., Valentino, P., Quattrone, A. Exosome‐associated miRNA profile as a prognostic tool for therapy response monitoring in multiple sclerosis patients. FASEB J . 32, 4241–4246 (2018). www.fasebj.org

Tumor-derived exosomes (TDEs) play a pivotal role in tumor establishment and progression, and are emerging biomarkers for tumor diagnosis in personalized medicine. To date, there is a lack of efficient technology platforms for exosome isolation and characterization. Multiple myeloma (MM) is an incurable B-cell malignancy due to the rapid development of drug-resistance. MM-released exosomes express the immunoglobulin B-cell receptor (Ig-BCR) of the tumor B-cells, which can be targeted by Idiotype-binding peptides (Id-peptides). In this study, we analyzed the production of MM-released exosomes in the murine 5T33MM multiple myeloma model as biomarkers of tumor growth. To this end, we selected Id-peptides by screening a phage display library using as bait the Ig-BCR expressed by 5T33MM cells. By FACS, the FITC-conjugated Id-peptides detected the MM-released exosomes in the serum of 5T33MM-engrafted mice, levels of which are correlated with tumor progression at an earlier time point compared to serum paraprotein. These results indicate that Id-peptide-based recognition of MM-released exosomes may represent a very sensitive diagnostic approach for clinical evaluation of disease progression.

Immune activation and chronic inflammation are hallmark features of HIV infection causing T-cell depletion and cellular immune dysfunction in AIDS. Here, we addressed the issue whether HIV-1 Tat could affect T cell development and acute inflammatory response by generating a transgenic mouse expressing Tat in lymphoid tissue. Tat-Tg mice showed thymus atrophy and the maturation block from DN4 to DP thymic subpopulations, resulting in CD4⁺ and CD8⁺ T cells depletion in peripheral blood. In Tat-positive thymus, we observed the increased p65/NF-κB activity and deregulated expression of cytokines/chemokines and microRNA-181a-1, which are involved in T-lymphopoiesis. Upon LPS intraperitoneal injection, Tat-Tg mice developed an abnormal acute inflammatory response, which was characterized by enhanced lethality and production of inflammatory cytokines. Based on these findings, Tat-Tg mouse could represent an animal model for testing adjunctive therapies of HIV-1-associated inflammation and immune deregulation.