ABSTRACT
OBJECTIVE: Multiple sclerosis (MS) is a chronic neurodegenerative disease of the central nervous system. The most common disease phenotype is Relapsing-Remitting MS (RRMS). Beta interferons are the first line of RRMS patients' treatment. Interferon-inducible protein 16 (IFI16) as a DNA sensing molecule and its downstream complex stimulator of interferon genes (STING) play a critical role in the activation of type I interferons. Hence we aimed to evaluate the expression rate of IFI16 and STING in RRMS patients' blood under a different type of IFNß treatment. METHODS: In the present study, 99 individuals participated. The participants were divided into 4 groups: 28 control subjects, 25 new cases of RRMS patients, 25 RRMS patients treated with IFNß-1a (B1a), 21 RRMS patients treated with IFNß-1b (B1b). The EDTA-treated blood samples were taken and transferred at standard conditions to the Cellular and Molecular Research Center of Shahrekord University of Medical Sciences, RNA was extracted and converted into cDNA. To evaluate the expression of IFI16 and STING, the Real-Time PCR method using SYBR Green/ROX qPCR master mix was performed done. The level of genes expression was measured using 2-ΔΔCt method. The obtained data were analyzed using SPSS v22 software. RESULTS: Comparison of the IFI and STING mRNA expression in blood samples in association with gender and age showed no significant differences (p>0.05). Also, the evaluation of IFI16 mRNA level revealed that the IFI16 genes' expressions were remarkably higher in the new case group compared to the control group, however, STING expression did not show any significant difference. The mRNA levels of IFI16 and STING in IFNß-treated groups were significantly lower than the new case group (p<0.001). Also, the genes' expressions in both the IFNß-treated groups were significantly lower compared to the control group (p<0.001). In the assessment of the correlation of IFI16 and STING expressions with age and sex in different research groups, no statistically significant differences were seen (p>0.05). CONCLUSION: Perhaps the IFNß therapy decreases the IFI16 and STING expression in a STINGdependent pathway as a negative feedback mechanism for regulation of the immune system and suppression of pro-inflammatory cytokines production. The important role of DNA sensing molecules and STING-dependent pathway in MS gives a new insight into future treatment based on STING-direct therapies.
Subject(s)
Membrane Proteins/genetics , Multiple Sclerosis, Relapsing-Remitting/genetics , Nuclear Proteins/genetics , Phosphoproteins/genetics , Adolescent , Adult , Blood Cells/drug effects , Blood Cells/metabolism , Case-Control Studies , Female , Gene Expression , Genetic Association Studies , Humans , Interferon-beta/therapeutic use , Iran , Male , Membrane Proteins/blood , Multiple Sclerosis, Relapsing-Remitting/blood , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Nuclear Proteins/blood , Phosphoproteins/blood , Young AdultABSTRACT
INTRODUCTION: Multiple sclerosis (MS) typically requires life-long management with disease-modifying therapies (DMTs). Many DMTs require regular self-injection, and can be associated with injection site reactions, pain, and needle/injection phobia-but these can be addressed by improvements in autoinjector design. The aim of this study was to investigate patient satisfaction and preference for BETACONNECT™ (Bayer Pharma AG), a novel interferon beta-1b autoinjector. METHODS: Patients in Germany performing self-injections using BETACONNECT took part in the study. Data were collected through an online 15-min structured survey. Participants rated their experience with BETACONNECT on a 6-point scale and those satisfied with BETACONNECT were asked to describe the reason using a free-text box. RESULTS: One-hundred and eighteen patients with MS completed the survey. Ninety percent preferred BETACONNECT to their previous injection method (only 4% previously used manual injections, so most had previously used other autoinjectors). Ninety-two percent were very confident/confident in their ability to perform an injection using BETACONNECT. The most common free-text responses to "Why are you satisfied with the BETACONNECT™ autoinjector?" were ease of use (46%), less irritation/pain at the injection site (33%), and smoother injections (24%). Features considered most useful were automated injections (98%), adjustable injection speed (98%), and adjustable injection depth (98%). Ninety-seven percent thought it was easy to know when an injection was complete and 95% agreed/strongly agreed it was easy to learn to use the autoinjector. Seventy-three percent agreed that the quietness and effortlessness of the BETACONNECT reduced their level of injection anxiety, 92% that its size and shape makes it easy to handle during injections, and 67% that it decreases injection site pain. Eighty percent of those using the reminder function thought they were less likely to miss an injection. CONCLUSION: Patients with MS self-injecting interferon beta-1b expressed a high level of satisfaction and preference for BETACONNECT. Thus, BETACONNECT represents a valid option to improve patients' overall injection experience. FUNDING: Bayer HealthCare Pharmaceuticals.