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Skin is the forestage for a series of many-sided functions of tumor necrosis factor-alpha (TNF-α), a proinflammatory cytokine with staggering versatility and sizable implications for tissue homeostasis, immune responses, angiogenesis, apoptosis, local and systemic inflammation. An aberrant TNF-α-mediated crosstalk has been linked to the pathogenesis of acute and chronic skin inflammatory diseases, and indeed, TNF-α dysregulation can contribute to the development and progression of psoriasis, vitiligo, local damage following exposition to ultraviolet light radiations, cutaneous lupus erythematosus, and acne vulgaris. Therapies that target TNF-α are conspicuously used in the treatment of different skin disorders, aiming to modulate the in vivo immune functions triggered by many cutaneous cells, including keratinocytes, mast cells, or Langerhans cells, and reduce inflammation taking place within the skin. Herein, we focus on the key relationships between TNF-α and distinct skin non-neoplastic inflammatory or physiologic conditions, showing that a natural induction of TNF-α may have a protective significance but that TNF-α overproduction may be harmful or even lethal. Many questions remain unraveled in the therapeutic practice, and caution should be exercised due to eventual backlashes exerted by TNF-α in maintaining skin health or in provoking skin disease.
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Piel , Factor de Necrosis Tumoral alfa , Factor de Necrosis Tumoral alfa/metabolismo , Humanos , Piel/metabolismo , Piel/patología , Piel/efectos de la radiación , Animales , Enfermedades de la Piel/metabolismo , Enfermedades de la Piel/etiología , Enfermedades de la Piel/patología , Inflamación/metabolismo , Inflamación/patologíaRESUMEN
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder affecting the peripheral nervous system. Despite the established diagnostic criteria, monitoring disease activity and treatment remains challenging. To address this limitation, we investigated serum neurofilament light chain (sNfL) and serum free light chains (sFLCs) as potential biomarkers. A total of 32 CIDP patients undergoing immunoglobulin therapy and 32 healthy controls enrolled in the present study, and agreed to have their blood plasma sNfL and sFLCs analyzed, while CIDP severity was assessed through the modified Rankin Scale (mRS) and the Overall Neuropathy Limitations Scale (ONLS). In line with the immunoglobulin treatment aimed at limiting neuronal damage administered to the majority of patients, sNfL levels did not exhibit significant differences between the two groups. However, CIDP patients showed significantly elevated sFLC and sFLC ratios, while the marker levels did not correlate with the clinical scores. The study confirms the potential of sFLCs as a sensitive biomarker of inflammatory processes in CIDP. Additionally, the present study results regarding neurofilaments strengthen the role of sNfL in monitoring CIDP treatments, confirming the effectiveness of immunoglobulin therapy. Overall, our results demonstrate how combining these markers can lead to better patient characterization for improved treatment.
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Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Humanos , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Filamentos Intermedios , Cadenas Ligeras de Inmunoglobulina , BiomarcadoresRESUMEN
Calprotectin (CLP) is a calcium-binding protein produced by neutrophils and monocytes in the course of inflammation. Today, the role of faecal CLP in chronic IBD is well known, but in recent years attention has shifted towards circulating CLP. In fact, this molecule can be measured in different biological fluids: blood, saliva and urine, using different analytic methods that are described in this review. Furthermore, different data confirm the relevant role of serum CLP in autoimmune diseases. In this review we will highlight the correlation between high levels of circulating CLP and specific autoantibodies of major autoimmune pathologies paving the way to the employment of CLP measurement as useful biomarker for monitoring outcome in different pathologies.
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Enfermedades Inflamatorias del Intestino , Complejo de Antígeno L1 de Leucocito , Humanos , Complejo de Antígeno L1 de Leucocito/análisis , Inflamación , Biomarcadores/metabolismo , Heces/química , Neutrófilos/metabolismoRESUMEN
Inflammation and inflammasomes have been proposed as important regulators of the host-microorganism interaction, playing a key role in morbidity and mortality due to the coronavirus disease 2019 (COVID-19) in subjects with chronic conditions and compromised immune system. The inflammasome consists of a multiprotein complex that finely regulates the activation of caspase-1 and the production and secretion of potent pro-inflammatory cytokines such as IL-1ß and IL-18. The pyrin containing NOD (nucleotide-binding oligomerization domain) like receptor (NLRP) is a family of intracellular receptors, sensing patterns associated to pathogens or danger signals and NLRP3 inflammasome is the most deeply analyzed for its involvement in the innate and adaptive immune system as well as its contribution to several autoinflammatory and autoimmune diseases. It is highly expressed in leukocytes and up-regulated in sentinel cells upon inflammatory stimuli. NLRP3 expression has also been reported in B and T lymphocytes, in epithelial cells of oral and genital mucosa, in specific parenchymal cells as cardiomyocytes, and keratinocytes, and chondrocytes. It is well known that a dysregulated activation of the inflammasome is involved in the pathogenesis of different disorders that share the common red line of inflammation in their pathogenetic fingerprint. Here, we review the potential roles of the NLRP3 inflammasome in cardiovascular events, liver damage, pulmonary diseases, and in that wide range of systemic inflammatory syndromes named as a cytokine storm.
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Síndrome de Liberación de Citoquinas , Cardiopatías , Inflamasomas , Hepatopatías , Enfermedades Pulmonares , Proteína con Dominio Pirina 3 de la Familia NLR , Humanos , Proteínas Portadoras/metabolismo , Síndrome de Liberación de Citoquinas/inmunología , Inflamasomas/metabolismo , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Enfermedades Pulmonares/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Cardiopatías/inmunología , Hepatopatías/inmunologíaRESUMEN
Systemic sclerosis (SSc) patients have an increased frequency of CD21low B cells and of serum interleukin-4 (IL-4) and IL-21, each possible markers of joint involvement in inflammatory arthritis. The aim of this study was to investigate the possible influence of CD21low B cells, IL-4, and IL-21 on joint involvement in a cohort of 52 SSc patients. The DAS28-ESR was correlated with CD21low B cells (r = 0.452, p < 0.001), IL-4 (r = 0.478, p < 0.001), and IL-21 (r = 0.415, p < 0.001). SSc patients with a DAS28-ESR > 3.2 had more CD21low B cells (12.65% (IQR: 7.11-13.79) vs. 5.08% (IQR: 3.76-7.45), p < 0.01), higher IL-4 levels (132.98 pg/mL (IQR: 99.12-164.12) vs. 100.80 pg/mL (IQR: 62.78-121.13), p < 0.05), and higher IL-21 levels (200.77 pg/mL (IQR: 130.13-302.41) vs. 98.83 pg/mL (IQR: 35.70-231.55), p < 0.01) than patients with a DAS28-ESR ≤ 3.2. The logistic regression analysis models showed that the DAI (OR: 2.158 (95% CI: 1.120; 4.156), p < 0.05) and CD21low B cells (OR: 1.301 (95% CI: 1.099; 1.540), p < 0.01), the DAI (OR: 2.060 (95% CI: 1.082; 3.919), p < 0.05) and IL-4 level (OR: 1.026 (95% CI: 1.006; 1.045), p < 0.01), and the DAI (OR: 1.743 (95% CI: 1.022; 2.975), p < 0.05) and IL-21 level (OR: 1.006 (95% CI: 1.000; 1.011), p < 0.05) were independently associated with a DAS28-ESR > 3.2. An elevated CD21low B cell percentage, IL-4 level, and IL-21 level was associated with higher articular disease activity in patients, suggesting a possible role in the pathogenesis of SSc joint involvement.
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Interstitial lung disease (ILD) is a life-threatening complication of systemic sclerosis (SSc). Type 2 (Th2) cytokines play a pivotal role in airway disease. Study aim was to evaluate serum level of Th2 interleukin (IL) and chemokine in SSc-ILD. Serum levels of IL-4, IL-5, IL-11, IL-13, IL-21, IL-31 and CXCL-13 were measured by Bio-Plex Multiplex Immunoassays in 60 SSc patients and 20 healthy controls (HC). Pulmonary function tests with diffusion lung capacity for carbon monoxide (DLco) and high resolution computed tomography (HRCT) were performed in SSc patients. ILD is defined as fibrotic changes (ground glass, reticular and honeycombing), assessed by Computer-Aided Lung Informatics for Pathology Evaluation and Ratings (CALIPER) software, affecting at least 10% of the lungs. Serum levels of Th2 cytokines were higher in SSc patients than HC. A linear correlation was observed between ground glass and IL-13 (r = 0.342, p < 0.01), IL-21 (r = 0.345, p < 0.01), IL-31 (r = 0.473, p < 0.001), IL-4 (r = 0.863, p < 0.001), IL-5 (r = 0.249, p < 0.05) and peripheral blood eosinophils (r = 0.463, p < 0.001). We found a negative correlation between DLco and IL-4 (r = - 0.511, p < 0.001) and peripheral blood eosinophils (r = - 0.446, p < 0.001). In the logistic regression analysis, IL-4 is associated with DLco ≤ 60% of the predicted [OR 1.039 (CI 95%: 1.015-1.064), p < 0.001], whilst mRSS [OR 1.138 (CI 95%: 1.023-1.266), p < 0.05] and IL-4 [OR 1.017 (CI 95%: 1-1.034), p < 0.05] were associated with ILD. Th2 inflammation could play a key role in early phase of SSc-ILD.
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Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Citocinas , Interleucina-13 , Interleucina-4 , Interleucina-5 , Enfermedades Pulmonares Intersticiales/etiología , Pulmón/patologíaRESUMEN
Prolonged B cells stimulation due to the Hepatitis C virus (HCV) can result in autoimmunity, stigmatized by rising levels of cryoglobulins (CGs), the rheumatoid factor (RF), and free light chains (FLC) of immunoglobulins (Ig) associated with a range of symptoms, from their absence to severe cryoglobulinemic vasculitis and lymphoma. Here, we aimed to identify an immunological signature for the earliest stages of vasculitis when cryoprecipitate is still not detectable. We firstly analyzed the IgG subclasses, FLC, and RF in 120 HCV-RNA-positive patients divided into four groups according to the type of cryoprecipitate and symptoms: 30 asymptomatic without cryoprecipitate (No Cryo), 30 with vasculitis symptoms but without CGs that we supposed were circulating but still not detectable (Circulating), 30 type II and 30 type III mixed cryoglobulinemia (Cryo II and Cryo III, respectively). Our results revealed that patients with supposed circulating CGs displayed a pattern of serological parameters that closely resembled Cryo II and Cryo III, with a stronger similarity to Cryo II. Accordingly, we analyzed the groups of Circulating and Cryo II for their immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements, finding a similar mixed distribution of monoclonal, oligoclonal, and polyclonal responses compared to a control group of ten HCV-RNA-negative patients recovered from infection, who displayed a 100% polyclonal response. Our results strengthened the hypothesis that circulating CGs are the origin of symptoms in HCV-RNA-positive patients without cryoprecipitate and demonstrated that an analysis of clonal IGH and TCR rearrangements is the best option for the early diagnosis of extrahepatic complications.
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Crioglobulinemia , Crioglobulinas , Hepatitis C Crónica , Vasculitis , Vasculitis/diagnóstico , Vasculitis/inmunología , Vasculitis/virología , Humanos , Masculino , Femenino , Crioglobulinemia/diagnóstico , Crioglobulinemia/virología , Crioglobulinas/análisis , Factor Reumatoide/sangre , Inmunoglobulinas/sangre , Hepatitis C Crónica/sangre , Hepatitis C Crónica/complicacionesRESUMEN
Infectious diseases such as HIV and HBV are a global concern for their impact in terms of public health and costs for national health services. A central role in contrasting the spread of the infections is represented by timely diagnosis. The speed of detection depends on several factors including the type of test used. Antibody response to hepatitis B surface antigens (anti-HBs) is an important serological marker used for HBV-infection detection. The aim of this study was to compare the performance of the Abbott system and of the new analyser Mindray 1200i in the detection of HBV- and HIV-infections. Clinical serum samples were collected from patients randomly selected from PTV University Hospital of University of Rome "Tor Vergata" and tested for HBV and HIV antibodies. Samples were evaluated by Mindray Cl 1200i CLIA screening tests for HBV and HIV and the results were compared with the Abbott Architect analytical system, the routine instrument of the hospital clinical biochemistry laboratory. Precision study, linearity, and carryover were performed on the results obtained. The agreement between the results of the Abbott and Mindray CLIA ranged from 99% to 100% and the discrepancy rate from 0% to 1%. The measurements demonstrated that the Mindray CL-1200i platform offers high-level performance with accurate and consistent test results and could represent a valuable tool if implemented in routine analysis.
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The antibody-related immune response is mediated by immunoglobulins (Igs), soluble circulating glycoproteins produced by activated B cells that, upon the recognition of specific epitopes on pathogen surfaces, activate, proliferate, and differentiate into antibody-secreting plasma cells. Although the antibodies are effectors of the humoral immune adaptive response, their overproduction in response to a dysregulated proliferation of clonal plasma cell production in tumoral conditions (i.e., multiple myeloma), enriches the serum and urinary matrices, assuming the crucial role of biomarkers. Multiple myeloma (MM) is a plasma cell dyscrasia characterized by the expansion and accumulation of clonally activated plasma cells in bone marrow, determining the release of high amounts of monoclonal component (MC) that can be detected as intact immunoglobulin (Ig), immunoglobulin fragments, or free light chains (FLCs). The importance of detecting biomarkers for the diagnosis, monitoring, and prognosis of diseases is highlighted by the international guidelines that recommend specific assays for the analysis of intact Igs and FLC. Moreover, a developed assay called Hevylite® allows for the quantification of immunoglobulins that are both involved (iHLC) and not involved (uHLC) in the tumor process; this is a fundamental aspect of following up the patient's workup and evaluating the progression of disease, together with the treatments response. We here summarize the major points of the complex scenario involving monoclonal gammopathies and MM clinical management in view of advantages derived for the use of Hevylite®.
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Back pain is the leading cause of disability worldwide. Its emergence relates not only to the musculoskeletal degeneration biological substrate but also to psychosocial factors; emotional components play a pivotal role. In modern society, people are significantly informed by the Internet; in turn, they contribute social validation to a "successful" digital information subset in a dynamic interplay. The Affective component of medical pages has not been previously investigated, a significant gap in knowledge since they represent a critical biopsychosocial feature. We tested the hypothesis that successful pages related to spine pathology embed a consistent emotional pattern, allowing discrimination from a control group. The pool of web pages related to spine or hip/knee pathology was automatically selected by relevance and popularity and submitted to automated sentiment analysis to generate emotional patterns. Machine Learning (ML) algorithms were trained to predict page original topics from patterns with binary classification. ML showed high discrimination accuracy; disgust emerged as a discriminating emotion. The findings suggest that the digital affective "successful content" (collective consciousness) integrates patients' biopsychosocial ecosystem, with potential implications for the emergence of chronic pain, and the endorsement of health-relevant specific behaviors. Awareness of such effects raises practical and ethical issues for health information providers.
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Algoritmos , Ecosistema , Humanos , Aprendizaje Automático , Emociones , Dolor de Espalda , InternetRESUMEN
The aim was to evaluate the longitudinal association between basal serum adiponectin and repeated measurements of skin thickness during 12 months of follow-up in systemic sclerosis (SSc) patients. We enrolled SSc patients with disease duration > 2 years in a prospective observational study. Skin thickness was measured at baseline and after 12 months of follow-up with modified Rodnan skin score (mRSS). Baseline serum adiponectin was determined using a commercial ELISA kit. We enrolled 66 female SSc patients (median age 54 years, IQR 42−62 years). The median disease duration was 12 (IQR 8−16) years and median baseline serum adiponectin was 9.8 (IQR 5.6−15.6) mcg/mL. The median mRSS was 10 (IQR 6−18) at baseline and 12 (IQR 7−18) at follow-up. A significant correlation was observed between baseline serum adiponectin and disease duration (r = 0.264, p < 0.05), age (r = 0.515, p < 0.0001), baseline mRSS (r = −0.303, p < 0.05), and mRSS at follow-up (r = −0.322, p < 0.001). In multiple regression analysis, only mRSS at follow-up showed an inverse correlation with baseline serum adiponectin (ß = −0.132, p < 0.01). The reduction in serum adiponectin levels is correlated with skin thickness.
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OBJECTIVE: to assess the influence of SARS-CoV-2 mRNA vaccine on B-cell phenotypes in systemic sclerosis (SSc). METHODS: peripheral blood B-cell subpopulations were evaluated before (t1) and 3 months (t3) after the second dose of vaccine in 28 SSc patients. Peripheral blood B-cell subpopulations were evaluated in 21 healthy controls (HCs) only at t1. Anti-spike IgG levels were evaluated at t3 in both cohorts. RESULTS: SSc patients presented higher naive, double-negative, and CD21low B cells compared to HCs. IgM-memory and switched-memory B cells were lower in SSc patients than HCs. No differences in anti-spike IgG levels after vaccination were observed between SSc patients and HCs. Anti-spike IgG levels after vaccination were lower in SSc patients with increased CD21low B cells at baseline compared to SSc patients with normal CD21low B cells. A positive correlation was found between IgG levels and naive B cells. A negative linear correlation was shown between IgG levels and IgM-memory, switched-memory, double-negative, and CD21low B cells. CONCLUSIONS: SARS-CoV-2 mRNA vaccine response is normal in SSc patients not undergoing immunosuppressive therapy. The normal number of naive B cells is a positive marker of antibody response. The increased percentage of CD21low B cells represents a negative marker of antibody response.
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Hepatocellular carcinoma (HCC) represents a worldwide health matter with a major care burden, high prevalence, and poor prognosis. Its pathogenesis mainly varies depending on the underlying etiological factors, although it develops from liver cirrhosis in the majority of cases. This review summarizes the role of the most interesting soluble factors as biomarkers for early diagnosis and as recommended targets for treatment in accordance with the new challenges in precision medicine. In the premalignant environment, inflammatory cells release a wide range of cytokines, chemokines, growth factors, prostaglandins, and proangiogenic factors, making the liver environment more suitable for hepatocyte tumor progression that starts from acquired genetic mutations. A complex interaction of pro-inflammatory (IL-6, TNF-α) and anti-inflammatory cytokines (TGF-α and -ß), pro-angiogenic molecules (including the Angiopoietins, HGF, PECAM-1, HIF-1α, VEGF), different transcription factors (NF-kB, STAT-3), and their signaling pathways are involved in the development of HCC. Since cytokines are expressed and released during the different stages of HCC progression, their measurement, by different available methods, can provide in-depth information on the identification and management of HCC.
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Aim of this work was to verify the analytical performance of thyroid panel tests measured by chemiluminescence immunoassay (CLIA) CL-1200i and to validate its efficacy as laboratory test for thyroid disorder.Serum samples were obtained by standard centrifugation, thawed and assayed in a blinded fashion, and in a single batch. This study compares the values of thyroid panel tests measured by Mindray CL-1200i chemiluminescent system to the Abbott platforms for TSH, FT3, FT4, and Beckman Coulter for Tg, TgAb, and TPOAb on patient serum samples. A total of 180 randomly selected patients including both hospitalized and ambulatory patients from the Policlinico Tor Vergata (PTV) of the University of Rome Tor Vergata were used. In all analyses performed, the thyroid panel tests of the Mindray platform showed discriminative ability to quantitatively assess the analyte involved in thyroid disease and disorder. This study verified that Mindray CL-1200i chemiluminescent system thyroid panel tests is a valid method for obtaining a quantitative analysis of thyroid disorders. It showed high diagnostic efficiency and could represent a valid tool with a potential reduction in time and workload for the diagnosis.
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Tiroxina , Triyodotironina , Humanos , Inmunoensayo/métodos , Luminiscencia , Glándula Tiroides , TirotropinaRESUMEN
Myasthenia gravis with antibodies (Abs) against the muscle-specific tyrosine kinase (MuSK) is a rare autoimmune disorder (AD) of the neuromuscular junction (NMJ) and represents a prototype of AD with proven IgG4-mediated pathogenicity. Thanks to the mechanism of Fab-arm exchange (FAE) occurring in vivo, resulting MuSK IgG4 k/λ Abs increase their interference on NMJ and pathogenicity. The characterization of hybrid MuSK IgG4 as a biomarker for MG management is poorly investigated. Here, we evaluated total IgG4, hybrid IgG4 k/λ, and the hybrid/total ratio in 14 MuSK-MG sera in comparison with 24 from MG with Abs against acetylcholine receptor (AChR) that represents the not IgG4-mediated MG form. In both subtypes of MG, we found that the hybrid/total ratio reflects distribution reported in normal individuals; instead, when we correlated the hybrid/total ratio with specific immune-reactivity we found a positive correlation only with anti-MuSK titer, with a progressive increase of hybrid/total mean values with increasing disease severity, indirectly confirming that most part of hybrid IgG4 molecules are engaged in the anti-MuSK pathogenetic immune-reactivity. Further analysis is necessary to strengthen the significance of this less unknown biomarker, but we retain it is full of a diagnostic-prognostic powerful potential for the management of MuSK-MG.
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Inmunoglobulina G/inmunología , Miastenia Gravis/inmunología , Proteínas Tirosina Quinasas Receptoras/inmunología , Receptores Colinérgicos/inmunología , Biomarcadores/sangre , Humanos , Inmunoglobulina G/sangre , Miastenia Gravis/sangre , Unión Neuromuscular/metabolismo , Unión Neuromuscular/patologíaRESUMEN
Cryoglobulinaemia consists of circulating monoclonal and/or polyclonal immunoglobulins with rheumatoid factor (RF) activity that precipitate at temperatures <37°C. Cryoglobulinaemic syndrome, characterised by clinical signs of systemic vasculitis, is associated with chronic infection of hepatitis C virus (HCV) and might evolve in B-cell malignancies. In about one third of all HCV infection cases, serum autoantibodies are commonly found. This is probably due directly to the transformation of infected B cells but, also, indirectly, to the viral chronic stimulation of a pool of autoreactive B cells. The pattern of IgG subclasses seems to contribute to the worsening progression of HCV infection into lymphoproliferative and/or autoimmune diseases. Many evidences showed that B cells circulating in patients with HCV-associated mixed cryoglobulinaemia (MC) are profoundly abnormal; moreover, in most of cases, normal B cells are replaced by expanded clonal B cells characterized by the low expression of CD21. After viral eradication, these cells persist in circulation and their occurrence does not correlate with serum cryoglobulins nor with vasculitis response or relapse. It is probably due to the persistence of monoclonal B cells producing RF, that in course of MC can be reactivated by circulating immune complexes, highly produced during infections or tumours. Here, we aimed to review current literature focusing the pathogenesis of MC referring to specificity and immunochemical characteristics of the immunoglobulins involved in cryoprecipitation.
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Crioglobulinemia , Hepatitis C , Inmunidad Adaptativa , Crioglobulinas , Hepacivirus , HumanosRESUMEN
Hepatitis C virus (HCV) represents the major risk factor for mixed cryoglobulinemia (MC), a small-vessel vasculitis that may evolve into an overt B-cell non-Hodgkin's lymphoma. Here, we aimed to identify a biomarker signature for the early diagnosis of minimal residual disease (MRD). We assessed free light chains (FLCs), IgM k,and IgM λ heavy/light chain (HLC) pairs, and vascular endothelial growth factor (VEGF) in sera from 34 patients with MC vasculitis (32 HCV- and 2 HBV-related), treated with low-dose rituximab (RTX). FLCs and IgM HLCs were measured by turbidimetric assay; VEGF by an enzyme-linked immunosorbent assay. After RTX, the positive (complete + partial) clinical and laboratory responses were of 85.29% and 50%, respectively; in contrast, the mean levels of FLCs, IgM HLCs, and VEGF were substantially unaffected in most patients and still above the normal range. In those achieving a reduction of FLCs and IgM k and λ chains values within the range of normality, we found that post-treatment free λ chains and IgM k values correlated with clinical and laboratory response. Our results suggest that high levels of FLCs, IgM HLCs, and VEGF could represent the signature of "dormant" B cell clones' activity that could be very useful to identify MRD indicative of possible relapse or worsening outcome.
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Crioglobulinemia , Inmunoglobulina M/sangre , Cadenas kappa de Inmunoglobulina/sangre , Cadenas lambda de Inmunoglobulina/sangre , Rituximab/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Crioglobulinemia/sangre , Crioglobulinemia/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In the natural history of SARS-CoV-2 infection, liver injury is frequent but quite mild and it is defined as any liver damage occurring during disease progression and treatment of infection in patients with or without pre-existing liver diseases. The underlying mechanisms for hepatic injury in patients with COVID-19 are still unclear but the liver damage in SARS-CoV-2 infection seems to be directly caused by virus-induced cytopathic effects. In this review, we will summarize all data of updated literature, regarding the relationship between SARS-CoV-2 infection, acute response and liver involvement. An overview will be given on liver injury, liver transplant and the possible consequences of COVID-19 in patients with pre-existing liver diseases.
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COVID-19/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Hepatopatías/inmunología , Hígado/inmunología , SARS-CoV-2/inmunología , Antivirales/inmunología , Antivirales/uso terapéutico , COVID-19/epidemiología , COVID-19/virología , Síndrome de Liberación de Citoquinas/metabolismo , Citocinas/inmunología , Citocinas/metabolismo , Hepatocitos/inmunología , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Hígado/patología , Hígado/fisiopatología , Hepatopatías/fisiopatología , Hepatopatías/terapia , Pandemias/prevención & control , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/fisiologíaRESUMEN
BACKGROUND: Synaptopathy is critical in pathophysiology of Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of neurogranin (NG) and amyloid-ß42 (Aß42) are considered markers of synaptic dysfunction in neurodegenerative diseases. OBJECTIVE: To evaluate the CSF synaptopathy-related biomarkers, especially the novel Aß42/NG ratio, in PD, establishing possible associations with cognitive level and other clinical parameters. METHODS: Levels of NG, Aß42, amyloid-ß40, total and phosphorylated tau, and Aß42/NG ratio were measured in 30 PD patients and 30 controls and correlated with cognitive and motor parameters. The accuracy in distinguishing the cognitive status was determined. RESULTS: NG and Aß42 were significantly reduced in PD, with higher NG levels in patients with worse cognition. The Aß42/NG ratio showed a direct correlation with Mini-Mental State Examination, independently from age and sex, and differentiated cognitively impaired patients with 92% sensitivity and 71.4% specificity, accuracy higher than NG alone. No correlations resulted with motor disturbances or therapy. CONCLUSIONS: The novel Aß42/NG ratio couples either presynaptic or postsynaptic markers of synaptic dysfunction, representing a potential global index of synaptopathy, useful to track cognitive functions in PD.