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Frontiers in Immunology 2019During the past years biologic agents (also termed biologicals or biologics) have become a crucial treatment option in immunological diseases. Numerous articles have...
During the past years biologic agents (also termed biologicals or biologics) have become a crucial treatment option in immunological diseases. Numerous articles have been published on biologicals, which complicates the decision making process on the use of the most appropriate biologic for a given immune-mediated disease. This systematic review is the first of a series of articles assessing the safety and efficacy of B cell-targeting biologics for the treatment of immune-mediated diseases. To evaluate rituximab's safety and efficacy for the treatment of immune-mediated disorders compared to placebo, conventional treatment, or other biologics. The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 4 October 2016 and 26 July 2018 concentrating on immune-mediated disorders. The literature search identified 19,665 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 105 articles were finally included in a narrative synthesis. Rituximab is both safe and effective for the treatment of acquired angioedema with C1-inhibitor deficiency, ANCA-associated vasculitis, autoimmune hemolytic anemia, Behçet's disease, bullous pemphigoid, Castleman's disease, cryoglobulinemia, Goodpasture's disease, IgG4-related disease, immune thrombocytopenia, juvenile idiopathic arthritis, relapsing-remitting multiple sclerosis, myasthenia gravis, nephrotic syndrome, neuromyelitis optica, pemphigus, rheumatoid arthritis, spondyloarthropathy, and systemic sclerosis. Conversely, rituximab failed to show an effect for antiphospholipid syndrome, autoimmune hepatitis, IgA nephropathy, inflammatory myositis, primary-progressive multiple sclerosis, systemic lupus erythematosus, and ulcerative colitis. Finally, mixed results were reported for membranous nephropathy, primary Sjögren's syndrome and Graves' disease, therefore warranting better quality trials with larger patient numbers.
Topics: Animals; Antigens, CD20; B-Lymphocytes; Disease Progression; Humans; Immune System Diseases; Immunotherapy; Lymphocyte Depletion; Rituximab; Treatment Outcome
PubMed: 31555262
DOI: 10.3389/fimmu.2019.01990 -
The Journal of Allergy and Clinical... Nov 2022During the first year of life, B-cell level is a valuable indicator of whether external factors, such as exposure to B-cell-depleting therapies, have an adverse impact... (Meta-Analysis)
Meta-Analysis
BACKGROUND
During the first year of life, B-cell level is a valuable indicator of whether external factors, such as exposure to B-cell-depleting therapies, have an adverse impact on immune system development. However, there are no standard reference ranges of B-cell levels in healthy infants by age.
OBJECTIVE
Our aim was to estimate the normal range of B-cell levels in infants, by age, during the first year of life by pooling data from published studies.
METHODS
Studies reporting B-cell levels measured by using flow cytometry and CD19 markers in healthy infants were identified via a systematic literature review. Quality and feasibility assessments determined suitability for inclusion in meta-analyses by age group and/or continuous age. Means and normal ranges (2.5th-97.5th percentile) were estimated for absolute and percentage B-cell levels. Sensitivity analyses assessed the impact of various assumptions.
RESULTS
Of the 37 relevant studies identified, 28 were included in at least 1 meta-analysis. The means and normal ranges of B-cell levels were found to be 707 cells/μL in cord blood (range 123-2324 cells/μL), 508 cells/μL in infants aged 0 to 1 month (range 132-1369 cells/μL), 1493 cells/μL in infants aged 1 to 6 months (range 416-3877 cells/μL), and 1474 cells/μL in infants older than 6 months (range 416-3805 cells/μL). The continuous age model showed that B-cell levels peaked at week 26. Trends were similar for the percentage B-cell estimates and in sensitivity analyses.
CONCLUSION
These meta-analyses provide the first normal reference ranges for B-cell levels in infants, by week of age, during the first year of life.
Topics: Infant; Humans; Reference Values; Flow Cytometry; B-Lymphocytes; Antigens, CD19
PubMed: 35728653
DOI: 10.1016/j.jaci.2022.06.006 -
The Cochrane Database of Systematic... Jun 2022Thyroid-associated ophthalmopathy (TAO) is the most frequent extrathyroidal manifestation of Graves' disease, affecting up to 50% of patients. It has a great impact on... (Review)
Review
BACKGROUND
Thyroid-associated ophthalmopathy (TAO) is the most frequent extrathyroidal manifestation of Graves' disease, affecting up to 50% of patients. It has a great impact on quality of life. Rituximab (RTX) is a human/murine chimeric monoclonal antibody that targets the CD20 receptor on B-lymphocytes. Preliminary work has shown that blocking this CD20 receptor with RTX may affect the clinical course of TAO by reducing inflammation and the degree of proptosis. OBJECTIVES: This review update, originally published in 2013, assesses the efficacy and safety of using RTX for the treatment of TAO.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2022, Issue 2), which contains the Cochrane Eyes and Vision Trials Register, Ovid MEDLINE, Ovid Embase, Latin American and Caribbean Health Science Information database (LILACS), the ISRCTN registry, clinicaltrials.gov and the WHO International Clinical Trials Registry Platform (WHO ICTRP). There were no language restrictions in the electronic search for trials. We last searched the electronic databases on 22 February 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of RTX administered by intravenous infusion using any dosage regimen for the treatment of active TAO in adults, compared to placebo or glucocorticoids treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently scanned titles and abstracts, and screened full-text reports of potentially relevant studies. The outcomes of interest in this review were: clinical activity score (CAS), NOSPECS severity scale, proptosis (mm), palpebral aperture (mm), extraocular motility (degrees or diplopia rating scale), quality of life and adverse effects.
MAIN RESULTS
We identified two studies that met the inclusion criteria in this updated review. Across both studies, the mean age of participants was 55 years and 77% were women. RTX compared to intravenous methylprednisolone (IVMP) One study, conducted in Italy, compared RTX (n = 15 after one participant withdrew) with IVMP (n = 16) for active TAO (CAS ≥ 3 out of 7 or 4 out of 10). We judged this study to be at low risk of bias in most domains, but it was stopped early because of disease reactivation in the comparator group (5/16 participants). This study provided low-certainty evidence that RTX may result in CAS improvement at 24 weeks compared to IVMP (15/15 versus 12/16 improved by ≥ 2 points; risk ratio (RR) 1.32, 95% confidence interval (CI) 0.98 to 1.78). Only very low-certainty evidence was available for the other outcomes: NOSPECS improvement by 2 or more classes (3/15 versus 3/16; RR 1.07, 95% CI 0.25 to 4.49); proptosis improvement by 2 mm or more (0/15 versus 1/16; RR 0.35, 95% CI 0.02 to 8.08); palpebral aperture improvement by 3 mm or more (2/15 versus 0/16; RR 5.31, 95% CI 0.28 to 102.38); motility improvement by 1 class or more (3/15 versus 3/16; RR 1.07, 95% CI 0.25 to 4.49); and improvement on the Graves' ophthalmopathy QoL scale by at least 6 points for "functioning" (5/14 versus 8/13; RR 0.58, 95% CI 0.25 to 1.32), and "appearance" (9/14 versus 6/13; RR 1.39, 95% CI 0.69 to 2.82). Adverse events were more common in the RTX group (RR 1.39, 95% CI 0.90 to 2.13; low-certainty evidence). Minor adverse effects (mild infusion reactions) were observed in most people receiving RTX at first infusion. Two participants experienced a major infusion reaction, likely cytokine release syndrome. RTX compared to placebo One study, conducted in the USA, enrolled 25 participants with active TAO (CAS ≥ 4 out of 7), comparing RTX (13 participants) to placebo. We judged this study to be at low risk of bias in most domains, but it was stopped early due to recruitment issues. It provided very low-certainty evidence on the following outcomes at 24 weeks: CAS improvement by 2 or more points (4/13 RTX versus 3/12 placebo; RR 1.23, 95% CI 0.34 to 4.40); NOSPECS improvement by 2 or more classes (2/13 versus 2/12; RR 0.92, 95% CI 0.15 to 5.56); proptosis improvement by 2 mm or more (2/13 versus 4/12; RR 0.46, 95% CI 0.10 to 2.08); palpebral aperture median change (0 mm in RTX group, in both eyes separately, versus -0.5 mm and 0.5 mm in placebo group right and left eye, respectively); motility median diplopia score (3 versus 2.5); SF-12 physical component median score (45.9 versus 40.3) and mental component median score (52.8 versus 46.1). More participants in the RTX group experienced adverse effects (8/13 versus 3/12; RR 2.46, 95% CI 0.84 to 7.18). AUTHORS' CONCLUSIONS: There is currently insufficient evidence to support the use of RTX in people with TAO. Future studies investigating RTX in people with active TAO may need to be multi-centre in order to recruit enough participants to make an adequate judgement on the efficacy and safety of this novel therapy.
Topics: Adult; Animals; Antibodies, Monoclonal; Diplopia; Female; Graves Ophthalmopathy; Humans; Male; Mice; Middle Aged; Rituximab
PubMed: 35709102
DOI: 10.1002/14651858.CD009226.pub3 -
Frontiers in Immunology 2023Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been FDA-approved, CAR T-cells targeting CD22, as well as dual-targeting CD19/CD22 CAR T-cells, are currently being evaluated in clinical trials. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD22-targeting CAR T-cell therapies. We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to March 3rd 2022 for full-length articles and conference abstracts of clinical trials employing CD22-targeting CAR T-cells in acute lymphocytic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The primary outcome was best complete response (bCR). A DerSimonian and Laird random-effects model with arcsine transformation was used to pool outcome proportions. From 1068 references screened, 100 were included, representing 30 early phase studies with 637 patients, investigating CD22 or CD19/CD22 CAR T-cells. CD22 CAR T-cells had a bCR of 68% [95% CI, 53-81%] in ALL (n= 116), and 64% [95% CI, 46-81%] in NHL (n= 28) with 74% and 96% of patients having received anti-CD19 CAR T-cells previously in ALL and NHL studies respectively. CD19/CD22 CAR T-cells had a bCR rate of 90% [95% CI, 84-95%] in ALL (n= 297) and 47% [95% CI, 34-61%] in NHL (n= 137). The estimated incidence of total and severe (grade ≥3) CRS were 87% [95% CI, 80-92%] and 6% [95% CI, 3-9%] respectively. ICANS and severe ICANS had an estimated incidence of 16% [95% CI, 9-25%] and 3% [95% CI, 1-5%] respectively. Early phase trials of CD22 and CD19/CD22 CAR T-cells show high remission rates in ALL and NHL. Severe CRS or ICANS were (1)rare and dual-targeting did not increase toxicity. Variability in CAR construct, dose, and patient factors amongst studies limits comparisons, with long-term outcomes yet to be reported.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42020193027.
Topics: Humans; Immunotherapy, Adoptive; T-Lymphocytes; Lymphoma, Non-Hodgkin; B-Lymphocytes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Sialic Acid Binding Ig-like Lectin 2
PubMed: 37180149
DOI: 10.3389/fimmu.2023.1178403 -
Advanced Drug Delivery Reviews 2020Vaccines are one of the most powerful technologies supporting public health. The adaptive immune response induced by immunization arises following appropriate activation...
Vaccines are one of the most powerful technologies supporting public health. The adaptive immune response induced by immunization arises following appropriate activation and differentiation of T and B cells in lymph nodes. Among many parameters impacting the resulting immune response, the presence of antigen and inflammatory cues for an appropriate temporal duration within the lymph nodes, and further within appropriate subcompartments of the lymph nodes- the right timing and location- play a critical role in shaping cellular and humoral immunity. Here we review recent advances in our understanding of how vaccine kinetics and biodistribution impact adaptive immunity, and the underlying immunological mechanisms that govern these responses. We discuss emerging approaches to engineer these properties for future vaccines, with a focus on subunit vaccines.
Topics: Adjuvants, Immunologic; B-Lymphocytes; Drug Carriers; Humans; Immunity, Humoral; Inflammation Mediators; Liposomes; Lymph Nodes; Nanoparticles; Plasmids; RNA, Messenger; T-Lymphocytes; Tissue Distribution; Vaccines
PubMed: 32598970
DOI: 10.1016/j.addr.2020.06.019 -
Asian Pacific Journal of Cancer... Dec 2023Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be...
INTRODUCTION
Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be limited by the emergence of chronic graft-versus-host disease (cGVHD). The clinical manifestations of cGVHD result from a complex immune response characterized by the involvement of both B and T cells. Ibrutinib, a pharmacological agent, acts as an inhibitor of Bruton's tyrosine kinase (BTK) pathway, which becomes activated through the B-cell receptor and regulates B-cell survival. By exerting inhibitory effects on both BTK and inhibitor of interleukin-2 inducible T-cell kinase (ITK), ibrutinib exhibits promise as a therapeutic approach for managing cGVHD. Ibrutinib may be considered as a viable treatment option for active cGVHD in cases where patients exhibit an inadequate response to corticosteroid-based therapies. This systematic review seeks to assess the efficacy and safety of ibrutinib in the context of cGVHD patient management.
METHOD
We incorporated search engines from PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. The study was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and Assessing The Methodological Quality of Systematic Review (AMSTAR). We used Risk of Bias- 2 (RoB-2) tool for assess the risk of bias in randomized controlled studies (RCTs) and Newcastle Ottawa Scale (NOS) for observational and open-label studies.
RESULTS
A total of 7 studies were included in this study consisted of four open-label studies, two retrospective cohort studies, and one RCT study. These studies compared Ibrutinitib with standard therapies. Two studies investigated the pediatric population, and five studies investigated the adult population. Overall, these studies reported the overall response rate (ORR) of ibrutinib for cGVHD were 54%-78%. The results showed that in pediatric patients, the ORR were 54-78%. The results also showed that in adult patients, the ORR were 67%-76%. The most common adverse effects observed across the seven studies included pyrexia, diarrhea, abdominal pain, cough, nausea, stomatitis, vomiting, headache, bleeding and bruising, infection, muscle aches, fatigue, oral bleeding, elevated transaminases, lower gastrointestinal bleeding, persistent dizziness, sepsis, pneumonia, reduced platelet count, exhaustion, sleeplessness, peripheral edema, and fatigue.
CONCLUSION
The majority of studies have indicated that ibrutinib exhibits a high ORR and provides long-lasting responses, while also having manageable side effects.
Topics: Adult; Humans; Child; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; B-Lymphocytes; Fatigue
PubMed: 38156834
DOI: 10.31557/APJCP.2023.24.12.4025 -
American Journal of Translational... 2019Normal B lymphocyte function and antibody secretion during inflammation can provide critical protection for the host. We aimed to synthesize existing evidence to explore... (Review)
Review
OBJECTIVE
Normal B lymphocyte function and antibody secretion during inflammation can provide critical protection for the host. We aimed to synthesize existing evidence to explore whether circulating B cells and plasma immunoglobulin M (IgM) levels were associated with survival during sepsis.
METHODS
PubMed, Embase, ISI Web of Knowledge, Cochrane Central Register of Controlled Trials were systematically searched. Studies with data on circulating B cells and plasma IgM levels within the initial 24 hours after sepsis onset were selected.
RESULTS
A total of 11 studies were qualified for inclusion in this systematic review and meta-analysis with a total of 829 patients with sepsis and/or septic shock. Number of circulating B cells was similar between septic patients and health controls (SMD = -1.81, 95% CI: -4.15, 0.54; P = 0.13, I = 99%), while it was significantly reduced in sepsis survivors versus sepsis non-survivors (SMD = -0.60, 95% CI: -0.87, -0.32; P < 0.0001, I = 0%). Concentration of plasma IgM level was significantly decreased in septic patients as compared with healthy controls. Also, the plasma IgM level was significantly lower in sepsis survivors versus sepsis non-survivors.
CONCLUSIONS
A poor prognostic survival outcome was observed for patients with decreased circulating B cells as well as IgM levels within the initial 24 h after sepsis onset.
PubMed: 31934274
DOI: No ID Found -
Stem Cell Research & Therapy Jun 2022Primary Sjögren's syndrome (pSS) is a diffuse connective tissue disease characterized by the invasion of exocrine glands such as lacrimal and salivary glands, abnormal... (Review)
Review
Primary Sjögren's syndrome (pSS) is a diffuse connective tissue disease characterized by the invasion of exocrine glands such as lacrimal and salivary glands, abnormal proliferation of T and B lymphocytes, and infiltration of tissue lymphocytes. With the development of modern medicine, although research on the pathogenesis, diagnosis, and treatment of pSS has made significant progress, its pathogenesis has not been fully understood. Meanwhile, in the era of individualized treatment, it remains essential to further explore early diagnosis and treatment methods. Exosomes, small vesicles containing proteins and nucleic acids, are a subtype of extracellular vesicles secreted by various cells and present in various body fluids. Exosomes contribute to a variety of biological functions, including intercellular signal transduction and pathophysiological processes, and may play a role in immune tolerance. Therefore, exosomes are key to understanding the pathogenesis of diseases. Exosomes can also be used as a therapeutic tool for pSS because of their biodegradability, low immunogenicity and toxicity, and the ability to bypass the blood-brain barrier, implying the prospect of a broad application in the context of pSS. Here, we systematically review the isolation, identification, tracing, and mode of action of extracellular vesicles, especially exosomes, as well as the research progress in the pathogenesis, diagnosis, and treatment of pSS.
Topics: B-Lymphocytes; Exosomes; Extracellular Vesicles; Humans; Salivary Glands; Sjogren's Syndrome
PubMed: 35659085
DOI: 10.1186/s13287-022-02912-1 -
Diagnostics (Basel, Switzerland) Aug 2022Sepsis is a series of life-threatening organ dysfunction caused by an impaired host response to infection. A large number of molecular studies of sepsis have revealed... (Review)
Review
Sepsis is a series of life-threatening organ dysfunction caused by an impaired host response to infection. A large number of molecular studies of sepsis have revealed complex interactions between infectious agents and hosts that result in heterogeneous manifestations of sepsis. Sepsis can cause immunosuppression and increase the expression of checkpoint inhibitor molecules, including programmed death protein (PD-1) and programmed death ligand 1 (PD-L1), and thus PD-1 and PD-L1 are thought to be useful as diagnostic and prognostic tools for sepsis. PD-1 is an inhibitor of both adaptive and innate immune responses, and is expressed on activated T lymphocytes, natural killer (NK) cells, B lymphocytes, macrophages, dendritic cells (DCs), and monocytes, whereas PD-L1 is expressed on macrophages, some activated T and B cells, and mesenchymal stem cells as well as various non-hematopoietic cells. This systematic review aims to assess the PD-1 and PD-L1 protein expression levels and concentrations in septic and other infectious patients.
PubMed: 36010357
DOI: 10.3390/diagnostics12082004 -
Journal of Reproductive Immunology Aug 2022The fallopian tubes (FT) play a key role in fertility by facilitating the movement of gametes to promote fertilisation and, subsequently, passage of the zygote for... (Review)
Review
The fallopian tubes (FT) play a key role in fertility by facilitating the movement of gametes to promote fertilisation and, subsequently, passage of the zygote for implantation. Histologically, the FT mucosa consists of three main cell types: secretory, ciliated and peg cells. In addition, several studies have reported the presence of immune cells. This systematic review aims to present a comprehensive analysis of the immune cell populations in the human FT, both in health and benign pathology, to promote a better understanding of tubal pathologies and their influence on infertility. A comprehensive literature search was conducted across five databases and augmented with manual citation chaining. Forty-two eligible studies were selected in accordance with PRISMA guidelines. Following screening, risk of bias assessments were conducted, data extracted and the findings presented thematically. T lymphocytes, predominantly CD8 T cells, represent the most abundant immune cell population within the healthy FT, with B lymphocytes, macrophages, NK cells and dendritic cells also localised to the tubal mucosa. There is evidence to suggest that lymphocyte and macrophage populations are susceptible to changes in the concentration of reproductive hormones. Tubal ectopic pregnancy, salpingitis, hydrosalpinx and endometriosis are all characterised by an increased population of macrophages in comparison to healthy FT. However, given the inconsistent evidence presented between studies, and the lack of studies examining all immune cell subtypes in tubal pathologies, only limited conclusions can be formulated on pathology-specific immune cell populations, and further research is required for validation.
Topics: CD8-Positive T-Lymphocytes; Fallopian Tubes; Female; Humans; Mucous Membrane; Pregnancy; Pregnancy, Tubal; Salpingitis
PubMed: 35644062
DOI: 10.1016/j.jri.2022.103646