Real-World Coverage With Influenza, Pneumococcal, and Herpes Zoster Vaccines Among Patients With Rheumatic Diseases in a Nationwide Healthcare Plan.

OBJECTIVE: Vaccination against preventable infections is important for the management of rheumatic diseases (RDs). This study assessed the vaccination coverage and predictors among patients with RDs using real-world data from Israel. METHODS: This retrospective cross-sectional study, based on a Maccabi Healthcare Services database, included adult patients diagnosed with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and systemic lupus erythematosus (SLE), as of April 30, 2019. Age-specific vaccination coverage for influenza (past year), pneumococcal (23-valent pneumococcal polysaccharide vaccine [PPSV23] and/or 13-valent pneumococcal conjugate vaccine [PCV13]), and live-attenuated herpes zoster (HZ) vaccines (past 5 years) was reported. Logistic regression was used to investigate predictors of vaccination. RESULTS: The study included 14,528 patients (RA: n = 6932; PsA: n = 4395; SLE: n = 1951; > 1 condition: n = 1250). Influenza vaccine coverage among patients with RA, PsA, and SLE was 45.1%, 36.2%, and 33.7%, respectively. For PPSV23, corresponding rates were 19.6%, 16.2%, and 12.6%, respectively. In the elderly population (≥ 65 years), 63.2% had influenza vaccine in the past year and 83.4% had a PPSV23 vaccine in the past 5 years or at age ≥ 65. For PCV13 and HZ, coverage in the overall study population was low at 4.8% and 3.6%, respectively. Central residence and treatment with corticosteroids and biologic or targeted synthetic disease-modifying antirheumatic drugs within the past 5 years were significant predictors of vaccination coverage across all vaccines (P < 0.05). Other predictors varied by vaccine, including female sex (influenza, PPSV23, PCV13), age (influenza, PPSV23), chronic comorbidities (influenza, PPSV23, PCV13), shorter disease duration (PCV13), and high socioeconomic status (PCV13, HZ). CONCLUSION: This study demonstrated suboptimal coverage of influenza, pneumococcal, and HZ vaccination in patients with RA, PsA, and SLE, in particular among younger adults in Israel.

Transplantation of placenta-derived mesenchymal stem cells in the EAE mouse model of MS.

Stem cell-based regenerative medicine raises great hope for the treatment of multiple sclerosis (MS). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are being tested in clinical trials. Bone marrow is the traditional source of human MSCs, but human term placenta appears to be an excellent alternative because of its availability, without ethical issues. In this study, the therapeutic effect of human placental MSCs (PL-MSCs) was evaluated in experimental autoimmune encephalomyelitis (EAE), the mice model of MS. EAE mice were transplanted intra-cerebrally with PL-MSCs or with the vehicle saline 5 or 10 days after first MOG injection. The mice were monitored for a month after therapy. A daily EAE score revealed a decrease in disease severity in the transplanted animals when compared to saline. Survival was significantly higher in the transplanted animals. In vitro experiments demonstrated that conditioned media from LPS-activated astrocytes stimulated PL-MSCs to express the gene TNF-α-stimulated gene/protein 6 (TSG-6). The same mRNA expression was obtained when PL-MSCs were exposed to TNF-α or IL1-ß. These results demonstrate that PL-MSCs have a therapeutic effect in the EAE mice model. We assume that this effect is caused by reduction of the anti-inflammatory protein, TSG-6, of the inflammatory damage.

Placental mesenchymal stromal cells induced into neurotrophic factor-producing cells protect neuronal cells from hypoxia and oxidative stress.

BACKGROUND AIMS: Mesenchymal stromal cells (MSC) may be useful in a range of clinical applications. The placenta has been suggested as an abundant, ethically acceptable, less immunogenic and easily accessible source of MSC. The aim of this study was to evaluate the capacity of induced placental MSC to differentiate into neurotrophic factor-producing cells (NTF) and their protective effect on neuronal cells. METHODS: MSC were isolated from placentas and characterized by fluorescence-activated cell sorting (FACS). The cells underwent an induction protocol to differentiate them into NTF. Analysis of the cellular differentiation was done using polymerase chain reactions (PCR), immunocytochemical staining and enzyme-linked immunosorbent assays (ELISA). Conditioned media from placental MSC (PL-MSC) and differentiated MSC (PL-DIFF) were collected and examined for their ability to protect neural cells. RESULTS: The immunocytochemical studies showed that the cells displayed typical MSC membrane markers. The cells differentiated into osteoblasts and adipocytes. PCR and immunohistology staining demonstrated that the induced cells expressed typical astrocytes markers and neurotrophic factors. Vascular endothelial growth factor (VEGF) levels were higher in the conditioned media from PL-DIFF compared with PL-MSC, as indicated by ELISA. Both PL-DIFF and PL-MSC conditioned media markedly protected neural cells from oxidative stress induced by H(2)O(2) and 6-hydroxydopamine. PL-DIFF conditioned medium had a superior effect on neuronal cell survival. Anti-VEGF antibodies (Bevacizumab) reduced the protective effect of the conditioned media from differentiated and undifferentiated MSC. CONCLUSIONS: This study has demonstrated a neuroprotective effect of MSC of placental origin subjected to an induction differentiation protocol. These data offer the prospect of using placenta as a source for stem cell-based therapies.