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Frontiers in Immunology 2021Congenital heart diseases (CHDs) are diagnosed in approximately 9 in 1,000 newborns, and early cardiac corrective surgery often requires partial or complete thymectomy....
BACKGROUND AND AIMS
Congenital heart diseases (CHDs) are diagnosed in approximately 9 in 1,000 newborns, and early cardiac corrective surgery often requires partial or complete thymectomy. As the long-term effect of early thymectomy on the subsequent development of the immune system in humans has not been completely elucidated, the present study aimed to evaluate the effects of thymus removal on the functional capacity of the immune system after different periods.
METHODS
A systematic review of the literature was performed using MEDLINE, EMBASE, LILACS and Scopus. The inclusion criteria were original studies that analyzed any component of the immune system in patients with CHD who had undergone thymectomy during cardiac surgery in the first years of life. The results were evaluated for the quality of evidence.
RESULTS
Twenty-three studies were selected and showed that patients who underwent a thymectomy in the first years of life tended to exhibit important alterations in the T cell compartment, such as fewer total T cells, CD4+, CD8+, naïve and CD31+ T cells, lower TRECs, decreased diversity of the TCR repertoire and higher peripheral proliferation (increased Ki-67 expression) than controls. However, the numbers of memory T cells and Treg cells differed across the selected studies.
CONCLUSIONS
Early thymectomy, either partial or complete, may be associated with a reduction in many T cell subpopulations and TCR diversity, and these alterations may persist during long-term follow-up. Alternative solutions should be studied, either in the operative technique with partial preservation of the thymus or through the autograft of fragments of the gland.
SYSTEMATIC REVIEW REGISTRATION
Prospero [157188].
Topics: Age Factors; Antigenic Variation; Cell Proliferation; Child; Child Development; Child, Preschool; Humans; Immune System; Immunologic Memory; Infant; Infant, Newborn; Phenotype; Receptors, Antigen, T-Cell; T-Lymphocyte Subsets; Thymectomy; Thymus Gland; Treatment Outcome
PubMed: 34899730
DOI: 10.3389/fimmu.2021.774780 -
Clinical Nutrition ESPEN Dec 2021There are some studies indicating the effects of probiotic-containing foods or supplements on viral diseases. We aimed to conduct a rapid review of probiotics with... (Review)
Review
BACKGROUND & AIMS
There are some studies indicating the effects of probiotic-containing foods or supplements on viral diseases. We aimed to conduct a rapid review of probiotics with specific emphasis on their potential for early administration in patients at greater risk of SARS-CoV-2 infection.
METHODS
We searched on PubMed, EMBASE, Google Scholar, Science Direct, Scopus and Web of Science up to February 2021 to identify interventional and observational studies documenting the effects of probiotics strains on interleukins, virus titers, and antibody production with a focus on probiotic-containing foods (PROSPERO Registration ID. CRD42020181453) RESULTS: From a total of 163 records, 21 studies were classified into three domains based on the efficacy of probiotics on 1) the level of interleukins (n = 7), 2) virus titers (n = 2), and 3) interferon (IFN) and antibody production (n = 12). The suppuration of pro-inflammatory interleukins and type I INF production seemed to be the main anti-viral effect of probiotics. Nine studies also indicated the beneficial effects of probiotics and fermented foods on viral diseases.
CONCLUSION
Based on evidence, some probiotic strains may be useful in viral infections; randomized trials are needed to confirm these findings.
Topics: Antibody Formation; Humans; Probiotics; SARS-CoV-2; Viral Load; Virus Diseases; COVID-19 Drug Treatment
PubMed: 34857182
DOI: 10.1016/j.clnesp.2021.10.016 -
BioDrugs : Clinical Immunotherapeutics,... Nov 2021Immunogenicity with formation of anti-drug antibodies (ADA) to biologics is an important reason for treatment failure in inflammatory bowel disease (IBD). Our aim was to... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Immunogenicity with formation of anti-drug antibodies (ADA) to biologics is an important reason for treatment failure in inflammatory bowel disease (IBD). Our aim was to assess the rate of ADA, the effect of combination therapy with immunomodulators on ADA and the influence of ADA on efficacy and safety of biologics for IBD treatment.
METHODS
MEDLINE, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to April 2020 for trials of biologics that assessed immunogenicity. The overall certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). The primary outcome was rate of ADA. Secondary outcomes included efficacy and safety outcomes among patients with detectable versus undetectable ADA. For dichotomous outcomes, pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated.
RESULTS
Data from 68 studies were analyzed and 33 studies (5850 patients) were included in the meta-analysis. Pooled ADA rates for biologic monotherapy were 28.0% for infliximab, 7.5% for adalimumab, 3.8% for golimumab, 10.9% for certolizumab, 6.2% for ustekinumab and 16.0% for natalizumab. Pooled ADA rates were 8.4% for vedolizumab and 5.0% for etrolizumab for combo- and monotherapy combined. In all biologics, ADA rates were underestimated by use of drug-sensitive ADA assays and higher dose and/or frequency. ADA rate was significantly reduced in patients treated with combination therapy for infliximab (RR 0.52; 95% CI 0.44-0.62), adalimumab (RR 0.31; 95% CI 0.14-0.69), golimumab (RR 0.29; 95% CI 0.10-0.83), certolizumab pegol (RR 0.30; 95% CI 0.14-0.67) and natalizumab (RR 0.20; 95% CI 0.11-0. 39). ADA to infliximab were associated with lower clinical response rates (RR 0.75; 95% CI 0.61-0.91) and higher rates of infusion reactions (RR 2.36; 95% CI 1.85-3.01).
CONCLUSIONS
Differences in analytical methods to detect ADA hamper comparison of true ADA rates across biologics in IBD. Use of combination therapy with immunomodulators appeared to reduce ADA positivity for most biologics. For infliximab, ADA were associated with reduced drug efficacy and increased adverse events.
Topics: Adalimumab; Antibody Formation; Biological Factors; Humans; Inflammatory Bowel Diseases; Infliximab
PubMed: 34797516
DOI: 10.1007/s40259-021-00507-5 -
Drugs Nov 2021Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A (AGAL/GLA) gene. The lysosomal accumulation of the...
Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A (AGAL/GLA) gene. The lysosomal accumulation of the substrates globotriaosylceramide (Gb) and globotriaosylsphingosine (lyso-Gb) results in progressive renal failure, cardiomyopathy associated with cardiac arrhythmia, and recurrent strokes, significantly limiting life expectancy in affected patients. Current treatment options for FD include recombinant enzyme-replacement therapies (ERTs) with intravenous agalsidase-α (0.2 mg/kg body weight) or agalsidase-β (1 mg/kg body weight) every 2 weeks, facilitating cellular Gb clearance and an overall improvement of disease burden. However, ERT can lead to infusion-associated reactions, as well as the formation of neutralizing anti-drug antibodies (ADAs) in ERT-treated males, leading to an attenuation of therapy efficacy and thus disease progression. In this narrative review, we provide a brief overview of the clinical picture of FD and diagnostic confirmation. The focus is on the biochemical and clinical significance of neutralizing ADAs as a humoral response to ERT. In addition, we provide an overview of different methods for ADA measurement and characterization, as well as potential therapeutic approaches to prevent or eliminate ADAs in affected patients, which is representative for other ERT-treated lysosomal storage diseases.
Topics: Antibodies, Neutralizing; Antibody Formation; Enzyme Replacement Therapy; Fabry Disease; Humans; Injection Site Reaction; Isoenzymes; Lysosomal Storage Diseases; Male; Recombinant Proteins; Risk Factors; Trihexosylceramides; alpha-Galactosidase
PubMed: 34748189
DOI: 10.1007/s40265-021-01621-y -
Journal of Clinical Medicine Oct 2021Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure.... (Review)
Review
Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure. Both innate and adaptive immunity play a significant role in allograft tolerance. Therefore, immune cells, cytokines, and signal-transduction pathways are critical therapeutic targets. In this analysis, we aimed to review the current literature on various immunotherapeutic approaches for corneal-allograft rejection using the PubMed, EMBASE, Web of Science, Cochrane, and China National Knowledge Infrastructure. Retrievable data for meta-analysis were screened and assessed. The review, which evaluated multiple immunotherapeutic approaches to prevent corneal allograft rejection, showed extensive involvement of innate and adaptive immunity components. Understanding the contribution of this immune diversity to the ocular surface is critical for ensuring corneal allograft survival.
PubMed: 34682792
DOI: 10.3390/jcm10204667 -
Frontiers in Immunology 2021Sargramostim [recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF)] was approved by US FDA in 1991 to accelerate bone marrow recovery in...
BACKGROUND
Sargramostim [recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF)] was approved by US FDA in 1991 to accelerate bone marrow recovery in diverse settings of bone marrow failure and is designated on the list of FDA Essential Medicines, Medical Countermeasures, and Critical Inputs. Other important biological activities including accelerating tissue repair and modulating host immunity to infection and cancer the innate and adaptive immune systems are reported in pre-clinical models but incompletely studied in humans.
OBJECTIVE
Assess safety and efficacy of sargramostim in cancer and other diverse experimental and clinical settings.
METHODS AND RESULTS
We systematically reviewed PubMed, Cochrane and TRIP databases for clinical data on sargramostim in cancer. In a variety of settings, sargramostim after exposure to bone marrow-suppressing agents accelerated hematologic recovery resulting in fewer infections, less therapy-related toxicity and sometimes improved survival. As an immune modulator, sargramostim also enhanced anti-cancer responses in solid cancers when combined with conventional therapies, for example with immune checkpoint inhibitors and monoclonal antibodies.
CONCLUSIONS
Sargramostim accelerates hematologic recovery in diverse clinical settings and enhances anti-cancer responses with a favorable safety profile. Uses other than in hematologic recovery are less-well studied; more data are needed on immune-enhancing benefits. We envision significantly expanded use of sargramostim in varied immune settings. Sargramostim has the potential to reverse the immune suppression associated with sepsis, trauma, acute respiratory distress syndrome (ARDS) and COVID-19. Further, sargramostim therapy has been promising in the adjuvant setting with vaccines and for anti-microbial-resistant infections and treating autoimmune pulmonary alveolar proteinosis and gastrointestinal, peripheral arterial and neuro-inflammatory diseases. It also may be useful as an adjuvant in anti-cancer immunotherapy.
Topics: COVID-19; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunologic Factors; Immunotherapy; Neoplasms; Recombinant Proteins; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34484202
DOI: 10.3389/fimmu.2021.706186 -
International Journal of Molecular... Aug 2021In health, the non-recirculating nature and long-term persistence of tissue-resident memory T cells (TRMs) in tissues protects against invading pathogens. In disease,...
In health, the non-recirculating nature and long-term persistence of tissue-resident memory T cells (TRMs) in tissues protects against invading pathogens. In disease, pathogenic TRMs contribute to the recurring traits of many skin diseases. We aimed to conduct a systematic literature review on the current understanding of the role of TRMs in skin diseases and identify gaps as well as future research paths. EMBASE, PubMed, SCOPUS, Web of Science, Clinicaltrials.gov and WHO Trials Registry were searched systematically for relevant studies from their inception to October 2020. Included studies were reviewed independently by two authors. This study was conducted in accordance with the PRISMA-S guidelines. This protocol was registered with the PROSPERO database (ref: CRD42020206416). We identified 96 studies meeting the inclusion criteria. TRMs have mostly been investigated in murine skin and in relation to infectious skin diseases. Pathogenic TRMs have been characterized in various skin diseases including psoriasis, vitiligo and cutaneous T-cell lymphoma. Studies are needed to discover biomarkers that may delineate TRMs poised for pathogenic activity in skin diseases and establish to which extent TRMs are contingent on the local skin microenvironment. Additionally, future studies may investigate the effects of current treatments on the persistence of pathogenic TRMs in human skin.
Topics: CD8-Positive T-Lymphocytes; Humans; Immunologic Memory; Lymphoma, T-Cell, Cutaneous; Organ Specificity; Psoriasis; Skin; Skin Diseases; T-Lymphocytes; Vitiligo
PubMed: 34445713
DOI: 10.3390/ijms22169004 -
Nutrients Jul 2021Multiple health benefits have been ascribed to brown seaweeds that are used traditionally as dietary component mostly in Asia. This systematic review summarizes...
Multiple health benefits have been ascribed to brown seaweeds that are used traditionally as dietary component mostly in Asia. This systematic review summarizes information on the impact of brown seaweeds or components on inflammation, and inflammation-related pathologies, such as allergies, diabetes mellitus and obesity. We focus on oral supplementation thus intending the use of brown seaweeds as food additives. Despite the great diversity of experimental systems in which distinct species and compounds were tested for their effects on inflammation and immunity, a remarkably homogeneous picture arises. The predominant effects of consumption of brown seaweeds or compounds can be classified into three categories: (1) inhibition of reactive oxygen species, known to be important drivers of inflammation; (2) regulation, i.e., in most cases inhibition of proinflammatory NF-κB signaling; (3) modulation of adaptive immune responses, in particular by interfering with T-helper cell polarization. Over the last decades, several inflammation-related diseases have increased substantially. These include allergies and autoimmune diseases as well as morbidities associated with lifestyle and aging. In this light, further development of brown seaweeds and seaweed compounds as functional foods and nutriceuticals might contribute to combat these challenges.
Topics: Adaptive Immunity; Asia; Databases, Factual; Diet; Dietary Supplements; Functional Food; Humans; Hypersensitivity; Inflammation; Obesity; Reactive Oxygen Species; Seaweed; Vegetables
PubMed: 34444774
DOI: 10.3390/nu13082613 -
Life (Basel, Switzerland) Aug 2021Antiphospholipid syndrome (APS) is an autoimmune disease characterized by autoreactive B and T cells against β2-glycoprotein I (B2GPI), with vascular thrombosis or... (Review)
Review
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by autoreactive B and T cells against β2-glycoprotein I (B2GPI), with vascular thrombosis or obstetrical complications. Dendritic cells (DCs) are crucial in the generation of autoimmunity. Here, we conducted a comprehensive systematic review on the relationship between DC and APS. We performed a literature search of PubMed as of 26 March 2021. A total of 33 articles were extracted. DCs are pivotal in inducing inflammatory responses and orchestrating adaptive immunity. DCs contribute to the local inflammation regarding vascular thrombosis or obstetrical complications. Both B2GPI and antiphospholipid antibodies (aPL) can promote antigen presentation by DCs and the generation or maintenance of autoimmunity. In addition, plasmacytoid DC activation is enhanced by aPL, thereby augmenting the inflammatory response. In line with these findings, DC modulation appears promising as a future treatment for APS. In conclusion, our review indicated the crucial role of DCs in the pathogenesis of APS. Deeper understanding of the complex relationship would help in developing new treatment strategies.
PubMed: 34440545
DOI: 10.3390/life11080801 -
Expert Reviews in Molecular Medicine Aug 2021Otitis media (OM) is a common reason for children to be prescribed antibiotics and undergo surgery but a thorough understanding of disease mechanisms is lacking. We...
OBJECTIVE
Otitis media (OM) is a common reason for children to be prescribed antibiotics and undergo surgery but a thorough understanding of disease mechanisms is lacking. We evaluate the evidence of a dysregulated immune response in the pathogenesis of OM.
METHODS
A comprehensive systematic review of the literature using search terms [otitis media OR glue ear OR AOM OR OME] OR [middle ear AND (infection OR inflammation)] which were run through Medline and Embase via Ovid, including both human and animal studies. In total, 82 955 studies underwent automated filtering followed by manual screening. One hundred studies were included in the review.
RESULTS
Most studies were based on in vitro or animal work. Abnormalities in pathogen detection pathways, such as Toll-like receptors, have confirmed roles in OM. The aetiology of OM, its chronic subgroups (chronic OM, persistent OM with effusion) and recurrent acute OM is complex; however, inflammatory signalling mechanisms are frequently implicated. Host epithelium likely plays a crucial role, but the characterisation of human middle ear tissue lags behind that of other anatomical subsites.
CONCLUSIONS
Translational research for OM presently falls far behind its clinical importance. This has likely hindered the development of new diagnostic and treatment modalities. Further work is urgently required; particularly to disentangle the respective immune pathologies in the clinically observed phenotypes and thereby work towards more personalised treatments.
Topics: Animals; Anti-Bacterial Agents; Ear, Middle; Humans; Immunity; Otitis Media; Signal Transduction
PubMed: 34404500
DOI: 10.1017/erm.2021.10