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Blood Advances Jun 2021Establishing a diagnosis of aplastic anemia (AA) can be challenging, but it is absolutely critical to appropriate management, especially differentiating between acquired... (Review)
Review
Establishing a diagnosis of aplastic anemia (AA) can be challenging, but it is absolutely critical to appropriate management, especially differentiating between acquired and inherited forms of the disease. The hematology field requires updated diagnostic guidelines to ensure that appropriate clinical pathways are pursued for patients and their safety. There are increasing clinical options for patients with immunosuppressive therapy and transplant once the diagnosis is made. In a case-based format, this review emphasizes the newer data on molecular (somatic and germline) findings in AA and how they are (or are not) helpful during diagnosis. There are key details on somatic mutation profiles and stated evidence where available for prognostic and treatment indications. Germline details of newer syndromes are also outlined, which make this review modern and reflect areas of uncertainty for clinicians.
Topics: Anemia, Aplastic; Humans; Immunosuppression Therapy
PubMed: 34156438
DOI: 10.1182/bloodadvances.2021004345 -
Current Opinion in Rheumatology May 2016Ophthalmologists and rheumatologists frequently have a miscommunication among themselves, and as a result differ in their opinion for patients consulting them with... (Review)
Review
PURPOSE OF REVIEW
Ophthalmologists and rheumatologists frequently have a miscommunication among themselves, and as a result differ in their opinion for patients consulting them with retinal vasculitis. This report seeks to establish a common understanding of the term, retinal vasculitis, and to review recent studies on this diagnosis.
RECENT FINDINGS
The genetic basis of some rare forms of retinal vascular disease has recently been described. Identified genes include CAPN5, TREX1, and TNFAIP3; Behçet's disease is a systemic illness that is very commonly associated with occlusive retinal vasculitis; retinal imaging, including fluorescein angiography and other newer imaging modalities, has proven crucial to the identification and characterization of retinal vasculitis and its complications; although monoclonal antibodies to interleukin-17A or interleukin-1 beta failed in trials for Behçet's disease, antibodies to TNF-alpha, either infliximab or adalimumab, have demonstrated consistent benefit in managing this disease. Interferon treatment and B-cell depletion therapy via rituximab may be beneficial in certain types of retinal vasculitis.
SUMMARY
Retinal vasculitis is an important entity for rheumatologists to understand. Retinal vasculitis associated with Behçet's disease responds to monoclonal antibodies that neutralize TNF, but the many other forms of noninfectious retinal vasculitis may require alternate therapeutic management.
Topics: Disease Management; Fluorescein Angiography; Fundus Oculi; Humans; Immunosuppression Therapy; Retinal Vasculitis; Retinal Vessels; Rheumatic Diseases
PubMed: 26945335
DOI: 10.1097/BOR.0000000000000271 -
EBioMedicine Dec 2022Sepsis is an ill-defined syndrome yet is a leading cause of morbidity and mortality worldwide. The most recent consensus defines sepsis as life-threatening organ... (Review)
Review
Sepsis is an ill-defined syndrome yet is a leading cause of morbidity and mortality worldwide. The most recent consensus defines sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. However, this definition belies the complexity and breadth of immune mechanisms involved in sepsis, which are characterized by simultaneous hyperinflammation and immune suppression. In this review, we describe the immunopathogenesis of sepsis and highlight some recent pathophysiological findings that have expanded our understanding of sepsis. Sepsis endotypes can be used to divide sepsis patients in different groups with distinct immune profiles and outcomes. We also summarize evidence on the role of the gut microbiome in sepsis immunity. The challenge of the coming years will be to translate our increasing knowledge about the molecular mechanisms underlying sepsis into therapies that improve relevant patient outcomes.
Topics: Humans; Sepsis; Immunosuppression Therapy; Gastrointestinal Microbiome
PubMed: 36470832
DOI: 10.1016/j.ebiom.2022.104363 -
Frontiers in Immunology 2023As critical executors regulating many cellular operations, proteins determine whether living activities can be performed in an orderly and efficient manner. Precursor... (Review)
Review
As critical executors regulating many cellular operations, proteins determine whether living activities can be performed in an orderly and efficient manner. Precursor proteins are inert and must be modified posttranslationally to enable a wide range of protein types and functions. Protein posttranslational modifications (PTMs) are well recognized as being directly associated with carcinogenesis and immune modulation and have emerged as important targets for cancer detection and treatment. Lactylation (Kla), a novel PTM associated with cellular metabolism found in a wide range of cells, interacts with both histone and nonhistone proteins. Unlike other epigenetic changes, Kla has been linked to poor tumor prognosis in all current studies. Histone Kla can affect gene expression in tumors and immunological cells, thereby promoting malignancy and immunosuppression. Nonhistone proteins can also regulate tumor progression and treatment resistance through Kla. In this review, we aimed to summarize the role of Kla in the onset and progression of cancers, metabolic reprogramming, immunosuppression, and intestinal flora regulation to identify new molecular targets for cancer therapy and provide a new direction for combined targeted therapy and immunotherapy.
Topics: Humans; Histones; Immunosuppression Therapy; Carcinogenesis; Immunotherapy; Epigenesis, Genetic
PubMed: 37646027
DOI: 10.3389/fimmu.2023.1253064 -
Wounds : a Compendium of Clinical... Mar 2016Hyaluronic acid (HA), the main component of extracellular matrix, is considered one of the key players in the tissue regeneration process. It has been proven to modulate... (Review)
Review
Hyaluronic acid (HA), the main component of extracellular matrix, is considered one of the key players in the tissue regeneration process. It has been proven to modulate via specific HA receptors, inflammation, cellular migration, and angiogenesis, which are the main phases of wound healing. Studies have revealed that most HA properties depend on its molecular size. High molecular weight HA displays anti-inflammatory and immunosuppressive properties, whereas low molecular weight HA is a potent proinflammatory molecule. In this review, the authors summarize the role of HA polymers of different molecular weight in tissue regeneration and provide a short overview of main cellular receptors involved in HA signaling. In addition, the role of HA in 2 major steps of wound healing is examined: inflammation and the angiogenesis process. Finally, the antioxidative properties of HA are discussed and its possible clinical implication presented.
Topics: Anti-Inflammatory Agents; Humans; Hyaluronan Receptors; Hyaluronic Acid; Immunosuppression Therapy; Inflammation; Regeneration; Signal Transduction; Soft Tissue Injuries; Wound Healing
PubMed: 26978861
DOI: No ID Found -
Cytokine & Growth Factor Reviews Feb 2023Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis, a complicated immune response is initiated, which varies... (Review)
Review
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis, a complicated immune response is initiated, which varies over time with sustained excessive inflammation and immunosuppression. Identifying a promising way to orchestrate sepsis-induced immunosuppression is a challenge. Myeloid-derived suppressor cells (MDSCs) comprise pathologically activated neutrophils and monocytes with potent immunosuppressive activity. They play an important part in inhibiting innate and adaptive immune responses, and have emerged as part of the immune response in sepsis. MDSCs numbers are persistently high in sepsis patients, and associated with nosocomial infections and other adverse clinical outcomes. However, their characteristics and functional mechanisms during sepsis have not been addressed fully. Our review sheds light on the features and suppressive mechanism of MDSCs. We also review the potential applications of MDSCs as biomarkers and targets for clinical treatment of sepsis.
Topics: Humans; Myeloid-Derived Suppressor Cells; Sepsis; Immunosuppression Therapy; Immune Tolerance; Monocytes
PubMed: 35927154
DOI: 10.1016/j.cytogfr.2022.07.007 -
Clinical Infectious Diseases : An... Oct 2021Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for... (Review)
Review
Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for infection. The "net state of immune suppression" is a conceptual framework of all factors contributing to infectious risk. Assays that measure immune function in the immunosuppressed transplant recipient relative to infectious risk and allograft function are lacking. The best measures of integrated immune function may be quantitative viral loads to assess the individual's ability to control latent viral infections. Few studies address adjustment of immunosuppression during active infections; thus, confronted with infection in solid organ recipients, the management of immunosuppression is based largely on clinical experience. This review examines known measures of immune function and the immunologic effects of common immunosuppressive drugs and available studies reporting modification of drug regimens for specific infections. These data provide a conceptual framework for the management of immunosuppression during infection in organ recipients.
Topics: Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infections; Organ Transplantation
PubMed: 32803228
DOI: 10.1093/cid/ciaa1189 -
Blood Jan 2015Chronic graft-versus-host disease (GVHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HCT). The... (Review)
Review
Chronic graft-versus-host disease (GVHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HCT). The 2-year cumulative incidence of chronic GVHD requiring systemic treatment is ~30% to 40% by National Institutes of Health criteria. The risk of chronic GVHD is higher and the duration of treatment is longer after HCT with mobilized blood cells than with marrow cells. Clinical manifestations can impair activities of daily living and often linger for years. Hematology and oncology specialists who refer patients to centers for HCT are often subsequently involved in the management of chronic GVHD when patients return to their care after HCT. Treatment of these patients can be optimized under shared care arrangements that enable referring physicians to manage long-term administration of immunosuppressive medications and supportive care with guidance from transplant center experts. Keys to successful collaborative management include early recognition in making the diagnosis of chronic GVHD, comprehensive evaluation at the onset and periodically during the course of the disease, prompt institution of systemic and topical treatment, appropriate monitoring of the response, calibration of treatment intensity over time in order to avoid overtreatment or undertreatment, and the use of supportive care to prevent complications and disability.
Topics: Allografts; Chronic Disease; Female; Graft vs Host Disease; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Incidence; Male
PubMed: 25398933
DOI: 10.1182/blood-2014-08-551994 -
Blood Mar 2017Acquired severe aplastic anemia (SAA) is a rare hematologic disease associated with significant morbidity and mortality. Immune destruction of hemopoietic stem cells... (Review)
Review
Acquired severe aplastic anemia (SAA) is a rare hematologic disease associated with significant morbidity and mortality. Immune destruction of hemopoietic stem cells plays an important role in pathogenesis, as shown by successful treatment with immunosuppressive agents, leading to transfusion independence or complete recovery of peripheral blood counts in a proportion of patients. Growth factors can be combined with immunosuppressive therapy (IST) and may improve response rates, as recently shown with thrombopoietin analogs. Anabolic steroids may still play a role in combination with IST. The problem with IST is failure to respond and the development of late clonal disorders. Bone marrow transplantation (BMT) is the other therapeutic option: a matched sibling donor remains the best choice. For patients lacking a matched family donor, unrelated donors can be readily found, although mostly for patients of Caucasian origin. Other BMT options include unrelated cord blood or mismatched family donors. Acute and chronic graft-versus-host disease remain important complications of BMT. Patient age is a strong predictor of outcome for both IST and BMT, and must be considered when designing therapeutic strategies. Early diagnosis and treatment, as well as long-term monitoring, remain crucial steps for successful treatment of SAA.
Topics: Anemia, Aplastic; Bone Marrow Transplantation; Humans; Immunosuppression Therapy; Treatment Outcome
PubMed: 28096088
DOI: 10.1182/blood-2016-08-693481 -
Lupus Science & Medicine 2020Lupus nephritis (LN) is a severe manifestation of SLE, characterised by subendothelial and/or subepithelial immune complex depositions in the afflicted kidney, resulting... (Review)
Review
Lupus nephritis (LN) is a severe manifestation of SLE, characterised by subendothelial and/or subepithelial immune complex depositions in the afflicted kidney, resulting in extensive injury and nephron loss during the acute phase and eventually chronic irreversible damage and renal function impairment if not treated effectively. The therapeutic management of LN has improved during the last decades, but the imperative need for consensual outcome measures remains. In order to design trials with success potentiality, it is important to define clinically important short-term and long-term targets of therapeutic and non-therapeutic intervention. While it is known that early response to treatment is coupled with favourable renal outcomes, early predictors of renal function impairment are lacking. The information gleaned from kidney biopsies may provide important insights in this direction. Alas, baseline clinical and histopathological information has not been shown to be informative. By contrast, accumulating evidence of pronounced discrepancies between clinical and histopathological outcomes after the initial phase of immunosuppression has prompted investigations of the potential usefulness of per-protocol repeat kidney biopsies as an integral part of treatment evaluation, including patients showing adequate clinical response. This approach appears to have merit. Hopefully, clinical, molecular or genetic markers that reliably reflect kidney histopathology and portend the long-term prognosis will be identified. Novel non-invasive imaging methods and employment of the evolving artificial intelligence in pattern recognition may also be helpful towards these goals. The molecular and cellular characterisation of SLE and LN will hopefully result in novel therapeutic modalities, maybe new taxonomy perspectives, and ultimately personalised management.
Topics: Artificial Intelligence; Biomarkers; Biopsy; Female; Humans; Immunosuppression Therapy; Kidney; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Outcome Assessment, Health Care; Patient Outcome Assessment; Prognosis; Renal Insufficiency
PubMed: 32153796
DOI: 10.1136/lupus-2020-000389