Impact of exercise on markers of B cell-related immunity:A systematic review

Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin levels,but evidence-based conclusions on potential benefits for adaptive immunity are lacking.This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells,immunoglobulins,and markers of secretory immunity in human biofluids.Methods:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,MEDLINE,Web of Science,and Embase were searched on March 8,2023.Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions,immunoglobulin levels,salivary flow rate,or secretory immunoglobulin A secretion rate were included.Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise.Study characteristics,outcome measures,and statistically significant changes were summarized tabularly.Results:Of the 67 eligible studies,22 applied acute exercise and 45 applied exercise training.All included outcomes revealed significant alterations over time in acute exercise and exercise training context,but only a few investigations showed significant differences compared to control conditions.Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.Conclusion:B cell-related outcomes are altered by acute exercise and exercise training,but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities.Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.

Hepatitis C virus in human B lymphocytes transformed by Epstein-Barr virus in vitro by in situ reverse transcriptase-polymerase chain reaction

AIM To study persistence and replication ofheltitis C virus (HCV) in patients' peripheralblood mononuclear cells (PBMC) cultured invitro.METHODS Epstein-Barr virus (EBV) was usedto transform the hepatitis C virus from a HCVpositive patient to permanent lymphoblastoidcell lines (LCL). Positive and negative HCV RNAstrands of the cultured cells and growth mediawere detected by reverse transcriptase-polymerase chain reaction ( RT-PCR ) eachmonth. Core and NS5 proteins of HCV werefurther tested using immunohistochemical SPmethod and in situ RT-PCR.RESULTS HCV RNA positive strands wereconsistently detected the cultured cells for oneyear. The negative-strand RNA in LCL cells andthe positive-strand RNA in supernatants wereobserved intermittently. Immunohistochemicalresults medicated expression of HCV NS3 and Cproteins in LCL cytoplasm mostly. The positivesignal of PCR product was dark blue and mainlylocalized to the LCL cytoplasm. The RT-PCRsignal was eliminated by overnight RNasedigestion but not DNase digestion.CONCLUSION HCV may exist and remainfunctional in a cultured cell line for a longperiod.

Rituximab for the Treatment of Multiple Sclerosis: A Retrospective Observational Cohort in Morocco

Background: RITUXIMAB (RTX) is a chimeric anti-CD20 monoclonal antibody that has initially demonstrated efficacy in patients with B-cell lymphoma. Then, over time, it has demonstrated its efficacy in systemic inflammatory diseases and recently in neurological diseases such as multiple sclerosis (MS). Here we describe our experience with rituximab from one MS center from MOROCCO. Objectives: To investigate the safety and efficacy of Rituximab in MS in a Moroccan population. Methods: A retrospective uncontrolled observational single-center study from January 2017 to July 2020, was including all off-label Rituximab-treated patients with MS with at least 6 months of follow-up. Outcome data were collected and evaluated relapse rate, EDSS score, and adverse events (AEs) from the medical charts. Adverse events grade according to the Common Terminology Criteria for Adverse Events. Results: A total of 63 MS patients were treated with RTX, 47 patients were included, while 12 cases had just initiated treatment and 4 cases were lost to follow-up. The mean age of the patients was 39 ± 12 years with a female predominance (F/M: 1.6). All forms of MS were included, 83% of whom had relapsing-remitting MS. The duration of disease progression was 8 ± 5 years. Median EDSS before RTX initiation was 5.5 (0 - 7). 51% of patients were treated with RTX as second-line therapy after failure of other disease-modifying therapies, whereas 34% received it as first-line therapy. The annualized relapse rates decreased from 0.8 to 0.2 after RTX treatment. The Median EDSS remained unchanged at 71%. Radiological stability was noted in 83.7%, while 13.5% had a single new T2 lesion. Infusion-related AEs occurred during 27.6% of infusions and most were mild. Simple infection grades ≤ 2 were noted in 19%. Abortion occurred in only one patient. Conclusion: Our study confirms the usability of rituximab treatment for MS in the MOROCCO healthcare environment.

Value of the peripheral blood B-cells subsets in patients with ankylosing spondylitis

Background The role of B-cell remains an enigma in the pathogenesis of ankylosing spondylitis （AS）. This study aimed to investigate the distributions of B-cells and subsets in peripheral blood of AS patients and observe their changes in etanercept-treated AS patents. Methods We detected the proportions of CD19^＋ B-cell, naive B-cell （CD19^＋CD27）, memory B-cell （CD19^＋CD27dim） and plasmablast （CD19^＋CD27high） in peripheral blood of 66 patients with AS （39 at active stage, 27 at stable stage; 35 patients with peripheral joint involvement, 31 patients with axial involvement alone）, 30 patients with rheumatoid arthritis （RA） and 30 healthy volunteers using flow cytometry. And then we observed the changes of the above indexes of 39 active AS patients treated with etanercept in a randomized, double-blind, placebo-controlled trial. Results （1） Percentages of CD19^＋ B-cells in active or peripheral joint involvement AS patients increased more obviously than those in stable or axial involvement alone AS patients （both P=0.001）, and percentage of CD19^＋CD27high B-cells in AS patients with peripheral joint involvement was significantly higher than that in cases with axial involvement alone or healthy volunteers （P=0.005 and 0.006, respectively）; （2） The percentage of CD19~ B-cells in AS patients was positively correlated with Bath Ankylosing Spondylitis Disease Activity Index （BASDAI） scores, Patient＇s Global Assessment （PGA） scores, total back pain scores and nocturnal back pain scores （r=0.270, 0.255, 0.251 and 0.266, P=-0.029, 0.039, 0.042 and 0.031, respectively）; （3） At week 6 and week 12, there were no statistical differences of the percentages of B-cells and subsets between etanercept group and placebo group of AS patients （P 〉0.05）; the percentage of CD19^＋ B-cells in etanercept group was higher than that in healthy volunteers at week 12 （t=3.320, P=0.003）. Conclusions Misbalance is present in B-cells and some subsets in peripheral blood of active AS patients with peripheral joint involved. B-cells might play an important role in the pathogenesis of AS patients. The high percentage of CD19^＋ B-cells in active AS patients cannot be down-regulated after 12-week etanercept treatment.

异常的CD39/CD73/腺苷通路导致慢性乙型肝炎患者B细胞超活化和疾病进展

背景:乙肝病毒(HBV)感染患者B细胞超活化的机制尚不明确。本研究旨在评估CD39/CD37/腺苷通路在慢性乙型肝炎(CHB)患者中的临床特点。方法:我们检测了202例HBV感染患者B细胞CD39和CD73表达及腺苷产生情况。CpG+CD40配体刺激B细胞后,阻断或激活CD39/CD73/腺苷通路,然后通过流式细胞术检测B细胞活化表型结果:在具有高HBV DNA载量,HBeAg阳性,高HBsAg水平以及肝脏炎症活跃的CHB患者中,外周血B细胞的CD39和CD73表达降低,并且在HBeAg血清转化或HBsAg降低的完全应答者中逐步恢复。尽管进行了有效的抗病毒治疗,但完全应答者中活化记忆B细胞亚群和组织样记忆B细胞亚群的CD39和CD73表达并未增加。此外,在炎性肝脏中,肝内B细胞的CD39和CD73表达降低。在体外,CHB患者的B细胞显示产生CD39/CD73依赖性细胞外腺苷的能力明显降低。阻断腺苷生成后B细胞活化标志物表达增加。相反,二甲双胍通过调节腺苷酸活化蛋白激酶,激活CD39/CD73/腺苷通路,从而使B细胞活化标志物表达显著降低。结论:B细胞中CD39和CD73表达下调可导致CHB患者的高病毒负荷,加重肝脏炎性反应,并影响抗病毒疗效。异常的CD39/CD73/腺苷通路导致B细胞超活化。使用二甲双胍调节CD39/CD73/腺苷通路可能作为一种能够逆转HBV诱导的免疫发病机制的治疗选择。

Distinctive distribution of lymphocytes in unruptured and previously untreated brain arteriovenous malformation

Aim:To test the hypothesis that lymphocyte infiltration in brain arteriovenous malformation(bAVM)is not associated with iron deposition(indicator of micro-hemorrhage).Methods:Sections of unruptured,previously untreated bAVM specimens(n=19)were stained immunohistochemically for T-lymphocytes(CD3+),B-lymphocytes(CD20+),plasma cells(CD138+)and macrophages(CD68+).Iron deposition was assessed by hematoxylin and eosin and Prussian blue stains.Superficial temporal arteries(STA)were used as control.Results:Both T-lymphocytes and macrophages were present in unruptured,previously untreated bAVM specimens,whereas few B cells and plasma cells were detected.Iron deposition was detected in 8 specimens(42%;95%confidence intervals=20-67%).The samples with iron deposition tended to have more macrophages than those without(666±313 vs.478±174 cells/mm2;P=0.11).T-cells were clustered on the luminal side of the endothelial surface,on the vessel-wall,and in the perivascular regions.There was no correlation between T-lymphocyte load and iron deposition(P=0.88).No macrophages and lymphocytes were detected in STA controls.Conclusion:T-lymphocytes were present in bAVM specimens.Unlike macrophages,the load and location of T-lymphocytes were not associated with iron deposition,suggesting the possibility of an independent cell-mediated immunological mechanism in bAVM pathogenesis.