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Neutrophils release neutrophil extracellular traps (NETs) as a defense strategy in response to broad-spectrum infections and sterile triggers. NETs consist of a DNA scaffold decorated with antimicrobial peptides (AMPs) and enzymatically active proteases, including peptidyl arginine deiminase type 4 (PAD4). Susceptibility to infections and inflammatory dysregulation are hallmarks of alcohol-related liver disease (ALD). Sixty-two patients with ALD were prospectively recruited, and they were followed for 90 days. Twenty-four healthy volunteers served as the control group. PAD4 concentrations were quantified using immunoenzymatic ELISAs. Correlation coefficients between PAD4 blood concentrations and markers of systemic inflammation; liver dysfunction severity scores; and ALD complications were calculated. The receiver operating curves (ROCs) and their areas under the curve (AUCs) were checked in order to assess the accuracy of PAD4 expression in predicting the degree of liver failure and the development of ALD complications. Systemic concentrations of PAD4 were significantly increased in the patients with ALD in comparison with controls. PAD4 levels correlated with the standard markers of inflammation and revealed a good predictive AUC (0.76) for survival in the whole ALD group. PAD4 seems to be an inflammatory mediator and may be potentially applied as a predictor of patient survival in ALD.
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Biomarcadores , Hepatopatías Alcohólicas , Neutrófilos , Arginina Deiminasa Proteína-Tipo 4 , Humanos , Arginina Deiminasa Proteína-Tipo 4/metabolismo , Masculino , Femenino , Neutrófilos/metabolismo , Persona de Mediana Edad , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/patología , Adulto , Biomarcadores/sangre , Trampas Extracelulares/metabolismo , Anciano , Curva ROC , Estudios de Casos y ControlesRESUMEN
Paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS) is a new systemic inflammatory disease that mainly affects children. Its course in many features resembles that of acute rheumatic fever (ARF). Therefore, it is interesting that the experiences with ARF can be used in the management of patients with PIMS-TS. The aim of the article is to analyse the current data on PIMS-TS in relation to ARF. PIMS-TS and ARF are associated with an abnormal immune response to specific pathogens (SARS-CoV-2 and group A streptococcus, respectively). The main symptoms of both diseases are fever and cardiac involvement. Current therapy for PIMS-TS is based on anti-inflammatory treatment: intravenous immunoglobulin (first-line), intravenous glucocorticoids (second-line), or biological therapy (third-line; including interleukin [IL]-1 antagonists, IL-6 receptor blockers, and anti-tumour necrosis factor agents). Vaccination might be good prophylaxis, but the efficacy and safety of the vaccines against SARS-CoV-2 have not yet been established in children. Interesting insights may be gained by considering PIMS-TS in light of what is known of ARF due to their similar courses, but there are still many unanswered questions surrounding this disease and its pathogenesis.
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COVID-19/patología , Fiebre Reumática/patología , SARS-CoV-2/patogenicidad , Síndrome de Respuesta Inflamatoria Sistémica/patología , COVID-19/complicaciones , COVID-19/etiología , COVID-19/virología , Vacunas contra la COVID-19/inmunología , Citocinas/metabolismo , Glucocorticoides/uso terapéutico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Fiebre Reumática/microbiología , SARS-CoV-2/aislamiento & purificación , Streptococcus pyogenes/patogenicidad , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Tratamiento Farmacológico de COVID-19RESUMEN
NKT cells comprise three subsets-type I (invariant, iNKT), type II, and NKT-like cells, of which iNKT cells are the most studied subset. They are capable of rapid cytokine production after the initial stimulus, thus they may be important for polarisation of Th cells. Due to this, they may be an important cell subset in autoimmune diseases. In the current review, we are summarising results of NKT-oriented studies in major neurological autoimmune diseases-multiple sclerosis, myasthenia gravis, and Guillain-Barre syndrome and their corresponding animal models.
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Síndrome de Guillain-Barré/inmunología , Células Asesinas Naturales/inmunología , Esclerosis Múltiple/inmunología , Miastenia Gravis/inmunología , Células T Asesinas Naturales/inmunología , Animales , Síndrome de Guillain-Barré/patología , Humanos , Inflamación/inmunología , Inflamación/patología , Células Asesinas Naturales/patología , Esclerosis Múltiple/patología , Miastenia Gravis/patología , Células T Asesinas Naturales/patologíaRESUMEN
Multiple myeloma (MM) is a plasma cell neoplasm characterized by an abnormal proliferation of clonal, terminally differentiated B lymphocytes. Current approaches for the treatment of MM focus on developing new diagnostic techniques; however, the search for prognostic markers is also crucial. This enables the classification of patients into risk groups and, thus, the selection of the most optimal treatment method. Particular attention should be paid to the possible use of immune factors, as the immune system plays a key role in the formation and course of MM. In this review, we focus on characterizing the components of the immune system that are of prognostic value in MM patients, in order to facilitate the development of new diagnostic and therapeutic directions.
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Mieloma Múltiple/inmunología , Mieloma Múltiple/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Quimiocinas , Citocinas , Humanos , Factores Inmunológicos/uso terapéutico , Péptidos y Proteínas de Señalización Intercelular , Interferón gamma , Mieloma Múltiple/tratamiento farmacológico , Pronóstico , Factores de Necrosis TumoralRESUMEN
BACKGROUND: COVID-19, a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly presents as fever, cough, dyspnea, and myalgia or fatigue. Although the majority of patients with COVID-19 have mild symptoms, some are more prone to serious outcomes, including pneumonia, acute respiratory distress syndrome (ARDS), and even death. Hemophagocytic lymphohistiocytosis (HLH) is a severe, life-threatening inflammatory syndrome associated with intense cytokine release (also known as a "cytokine storm"). Similar to COVID-19, HLH is characterized by aggressive course leading to multi-organ failure. MAIN TEXT: The purpose of this review article is to draw attention to the possibility of the complication of HLH in patients with the severe course of COVID-19. Indeed, some of the clinical characteristics observed in the more severe cases of COVID-19 are reminiscent of secondary HLH (which can be triggered by infections, malignancies, rheumatological diseases, or autoimmune/immunodeficiency conditions). The pathogenesis of SARS-CoV-2 infection also suggests that HLH or a similar hyperinflammatory syndrome is the cause of the severe course of the infection. CONCLUSION: The pathogenesis and clinical symptoms of severe COVID-19 indicate that an increased inflammatory response corresponding to HLH is occurring. Therefore, patients with severe COVID-19 should be screened for hyperinflammation using standard laboratory tests to identify those for whom immunosuppressive therapy may improve outcomes.
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Infecciones por Coronavirus/complicaciones , Síndrome de Liberación de Citoquinas/virología , Linfohistiocitosis Hemofagocítica/virología , Neumonía Viral/complicaciones , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/terapia , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/terapia , Pandemias , Neumonía Viral/terapia , SARS-CoV-2RESUMEN
Toll-like-receptor (TLR) family members were detected in the central nervous system (CNS). TLR occurrence was noticed and widely described in glioblastomamultiforme (GBM) cells. After ligand attachment, TLR-4 reorients domains and dimerizes, activates an intracellular cascade, and promotes further cytoplasmatic signaling. There is evidence pointing at a strong relation between TLR-4 signaling and micro ribonucleic acid (miRNA) expression. The TLR-4/miRNA interplay changes typical signaling and encourages them to be a target for modern immunotherapy. TLR-4 agonists initiate signaling and promote programmed death ligand-1 (PD-1L) expression. Most of those molecules are intensively expressed in the GBM microenvironment, resulting in the autocrine induction of regional immunosuppression. Another potential target for immunotreatment is connected with limited TLR-4 signaling that promotes Wnt/DKK-3/claudine-5 signaling, resulting in a limitation of GBM invasiveness. Interestingly, TLR-4 expression results in bordering proliferative trends in cancer stem cells (CSC) and GBM. All of these potential targets could bring new hope for patients suffering from this incurable disease. Clinical trials concerning TLR-4 signaling inhibition/promotion in many cancers are recruiting patients. There is still a lot to do in the field of GBM immunotherapy.
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Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Proteínas de Punto de Control Inmunitario/metabolismo , MicroARNs/genética , Receptor Toll-Like 4/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Ensayos Clínicos como Asunto , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Inmunoterapia , Células Madre Neoplásicas/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Wnt/metabolismoRESUMEN
Recurrent infection with human alphaherpesvirus 1 (HHV-1) may be associated with immune exhaustion that impairs virus elimination. Thymic peptides enhance immune function and thus could overcome immune exhaustion. In this study, we investigated whether reactivation of herpes infections was associated with immune exhaustion. Moreover, we examined the impact of treatment with thymostimulin on the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) on T and B lymphocytes in patients suffering from recurrent HHV-1 reactivation. We also assessed the effector function of peripheral blood mononuclear cells (PBMCs) after stimulation with thymic peptides. We enrolled 50 women with reactivated HHV-1 infections and healthy volunteers. We measured the expression of various activation and exhaustion markers on the surface of PBMCs using flow cytometry. In ex vivo experiments, we measured the secretion of inflammatory cytokines by PBMCs cultured with thymostimulin. Compared with controls, patients with reactivated HHV-1 infections had increased percentages of CD3+ co-expressing CD25, an activation marker (p < 0.001). Moreover, these patients had increased percentages of CD4+ and CD8+ cells co-expressing the inhibitory markers PD-1 and PD-L1. In cultures of PBMCs from the patients, thymostimulin increased the secretion of interferon gamma (p < 0.001) and interleukin (IL)-2 (p = 0.023), but not IL-4 or IL-10.Two-month thymostimulin therapy resulted in no reactivation of HHV-1 infection during this period and the reduction of PD-1 and PD-L1 expression on the surface of T and B lymphocytes (p < 0.001). In conclusion, reactivation of herpes infection is associated with immune exhaustion, which could be reversed by treatment with thymic peptides.
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Adyuvantes Inmunológicos/uso terapéutico , Herpes Simple/tratamiento farmacológico , Herpesvirus Humano 1/efectos de los fármacos , Infección Latente/tratamiento farmacológico , Extractos del Timo/uso terapéutico , Adyuvantes Inmunológicos/farmacología , Adulto , Antivirales/farmacología , Antivirales/uso terapéutico , Células Cultivadas , Citocinas/inmunología , Femenino , Herpes Simple/inmunología , Herpesvirus Humano 1/inmunología , Humanos , Infección Latente/inmunología , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/inmunología , Extractos del Timo/farmacologíaRESUMEN
Based on genome sequencing, it is estimated that over 90% of genes stored in human genetic material are transcribed, but only 3% of them contain the information needed for the production of body proteins. This group also includes micro RNAs representing about 1%-3% of the human genome. Recent studies confirmed the hypothesis that targeting molecules called Immune Checkpoint (IC) open new opportunities to take control over glioblastoma multiforme (GBM). Detection of markers that indicate the presence of the cancer occupies a very important place in modern oncology. This function can be performed by both the cancer cells themselves as well as their components and other substances detected in the patients' bodies. Efforts have been made for many years to find a suitable marker useful in the diagnosis and monitoring of gliomas, including glioblastoma.
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Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , MicroARNs/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Genoma Humano/genética , Glioblastoma/diagnóstico , Glioblastoma/terapia , Glioma/diagnóstico , Glioma/genética , Glioma/terapia , Humanos , Oncología Médica/métodos , Oncología Médica/estadística & datos numéricos , Sensibilidad y EspecificidadRESUMEN
One of the major challenges faced by modern nephrology is the identification of biomarkers associated with histopathological patterns or defined pathogenic mechanisms that may assist in the non-invasive diagnosis of kidney disease, particularly glomerulopathy. The identification of such molecules may allow prognostic subgroups to be established based on the type of disease, thereby predicting response to treatment or disease relapse. Advances in understanding the pathogenesis of diseases, such as membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, IgA (immunoglobulin A) nephropathy, and diabetic nephropathy, along with the progressive development and standardization of plasma and urine proteomics techniques, have facilitated the identification of an increasing number of molecules that may be useful for these purposes. The growing number of studies on the role of TLR (toll-like receptor) receptors in the pathogenesis of kidney disease forces contemporary researchers to reflect on these molecules, which may soon join the group of renal biomarkers and become a helpful tool in the diagnosis of glomerulopathy. In this article, we conducted a thorough review of the literature on the role of TLRs in the pathogenesis of glomerulopathy. The role of TLR receptors as potential marker molecules for the development of neoplastic diseases is emphasized more and more often, as prognostic factors in diseases on several epidemiological backgrounds.
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Biomarcadores/metabolismo , Enfermedades Renales/metabolismo , Receptores Toll-Like/metabolismo , Animales , Humanos , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/patología , PronósticoRESUMEN
Alterations to the programmed cell death protein-1 (PD-1) pathway were previously shown to be involved in a poorer prognosis for patients with proliferative glomerulonephritis (PGN). Here, we investigated the association between several infectious agents and the expression of PD-1 and its ligand (PD-L1) on T and B lymphocytes in patients with PGN and nonproliferative glomerulonephritis (NPGN). A cohort of 45 newly-diagnosed patients (23 with PGN and 22 with NPGN) and 20 healthy volunteers was enrolled. The percentage of peripheral blood mononuclear cells expressing PD-1 and PD-L1 antigens was determined by flow cytometry. We found PD-1 and PD-L1 expression on T and B lymphocytes was higher in PGN patients than in NPGN patients and controls. We also found that reactivation of the Epstein-Barr virus (EBV) correlated with the expression of PD-1/PD-L1 antigens in patients with PGN. Further receiver operating characteristic analysis indicated that PD-1 expression could distinguish EBV-positive PGN patients from those with NPGN or healthy controls. The use of PD-1 expression as a non-invasive marker of PGN should be further investigated.
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Linfocitos B/metabolismo , Antígeno B7-H1/metabolismo , Infecciones por Virus de Epstein-Barr/complicaciones , Glomerulonefritis/virología , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T/metabolismo , Adulto , Anciano , Estudios de Casos y Controles , Infecciones por Virus de Epstein-Barr/inmunología , Femenino , Glomerulonefritis/inmunología , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Curva ROC , Regulación hacia Arriba , Adulto JovenRESUMEN
At present, secondary immune deficiencies have become a clinical problem, recognized in different specialties. The aim of this paper was to increase awareness and support the need for screening at-risk populations. Secondary immune deficiencies result in variety of conditions, but not all of them require immunoglobulin replacement therapy, as specific antibody response might be preserved. Moreover, the management of secondary immune deficiencies vary between countries and different medical disciplines. This literature review presents the most common causes and clinical presentation of secondary immunodeficiencies with predominant impaired antibody production. We present diagnostic guidelines for patients at-risk, with an emphasis on the role of prophylactic vaccination as a treatment and diagnostic tool. This review considers the specificity and disparities of the Polish healthcare system and ultimately, suggests that management teams should include a clinical immunologist experienced in the treatment of humoral immunodeficiencies.
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INTRODUCTION: Patients with psoriasis and psoriatic arthritis (PsA) have metabolic disturbances, which may be due to chronic inflammation. AIM: Because interleukin-6 (IL-6) regulates both metabolic and inflammatory processes, we evaluated IL-6 as a potential marker of inflammation and metabolic disturbances in psoriasis. MATERIAL AND METHODS: This study involved 93 patients with psoriasis, including 31 patients with concurrent PsA. We investigated whether serum markers of lipid metabolism and inflammation, including IL-6, were related to each other and to disease activity. RESULTS: We found that concurrent PsA was associated with higher serum concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and IL-6. In patients with psoriasis alone, the IL-6 serum concentration correlated positively with the concentrations of TC and LDL-c and with erythrocyte sedimentation rates (ESRs). Moreover, IL-6 concentrations tended to correlate positively with the percentage of the body area affected by psoriatic lesions. Among all patients, those with normal blood lipids had lower ESRs and IL-6 concentrations than patients with abnormal blood lipids. A logistic regression model showed that PsA, Psoriasis Area Severity Index (PASI), and ESR were significant predictors of the serum IL-6 concentration. CONCLUSIONS: Interleukin-6 may be an indicator of inflammatory activity in psoriasis. Moreover, IL-6 may be related to lipid abnormalities in patients with this disease.
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Programmed cell death receptor 1 (PD-1) is one of the major immune checkpoints. Due to the lack of reports on PD-1- and PD-L1-positive lymphocyte proportions in patients with recurrent furunculosis, we aimed to evaluate percentages of those cells in the peripheral blood and to assess their correlations with other lymphocyte subsets, and the level of cell activation measured by the expression of CD25 and CD69 molecules on T lymphocytes. We recruited 30 patients with recurrent furunculosis and 15 controls. The amount of 5â¯mL of peripheral blood was collected for laboratory tests. Patients with chronic furunculosis presented with the similar number of lymphocytes, CD4+ T lymphocytes, CD8+CD3+ T suppressor lymphocytes, and CD19â¯+ B lymphocytes to controls, but significant differences were found between subpopulation of those cells. Furunculosis patients had the significantly elevated percentage of lymphocytes with PD-1 and PD-L1 on their surface. Early onset of furunculosis was correlated with a higher percentage of CD19 + PD1 B lymphocytes. Greater number of skin lesions correlated with a decrease in the CD4PDL1+ cells, which subsequently was associated with an increase in the percentage of Treg cells, NKT cells, CD8+CD3+ lymphocytes and B lymphocytes. Changes in the proportion of immune cells may lead to reduced inflammatory reactions in patients with recurrent furunculosis. In the light of mechanisms of S. aureus invasion, the degree of immune impairments in the scope of adaptive immunity seems to play a significant role in the course of furunculosis. PD-1 and PD-L1 molecules change the host response and affect the ongoing inflammatory process.
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Antígenos CD19/inmunología , Linfocitos B/inmunología , Antígeno B7-H1/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Forunculosis/inmunología , Receptor de Muerte Celular Programada 1/inmunología , Adolescente , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Antígeno B7-H1/sangre , Femenino , Forunculosis/sangre , Forunculosis/microbiología , Humanos , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Lectinas Tipo C/metabolismo , Recuento de Linfocitos , Subgrupos Linfocitarios , Masculino , Persona de Mediana Edad , Células T Asesinas Naturales/inmunología , Receptor de Muerte Celular Programada 1/sangre , Infecciones Estafilocócicas/sangre , Infecciones Estafilocócicas/inmunología , Staphylococcus aureus/inmunología , Staphylococcus aureus/patogenicidad , Linfocitos T Reguladores/inmunología , Adulto JovenRESUMEN
Despite the ongoing progress in cancer research, the global cancer burden has increased to 18.1 million new cases and 9.6 million deaths in 2018. Gynecological cancers, such as ovarian, endometrial, and cervical cancers, considerably contribute to global cancer burden, leading to $5,862.6, $2,945.7, and $1,543.9 million of annual costs of cancer care, respectively. Thus, the development of effective therapies against gynecological cancers is still a largely unmet medical need. One of the novel therapeutic approaches is to induce anti-cancer immunity by the inhibition of the immune checkpoint pathways using monoclonal antibodies. The molecular targets for monoclonal antibodies are cytotoxic T lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1). The rationale for the use of immune checkpoint inhibitors in patients with gynecological cancers was based on the immunohistological studies showing high expression levels of PD-1 and PD-L1 in those cancers. Currently available immune checkpoint inhibitors include nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and ipilimumab. The efficacy and safety of these inhibitors, used as monotherapy and with combination with chemotherapy, is being currently evaluated in several clinical studies. As the results are promising, more clinical trials are being planned, which may lead to the development of efficient therapies for gynecological cancer patients.
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Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de los Genitales Femeninos , Proteínas de Neoplasias , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/inmunología , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Neoplasias de los Genitales Femeninos/inmunología , Humanos , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/inmunologíaRESUMEN
Glioblastoma (GBM) is the most popular primary central nervous system cancer and has an extremely expansive course. Aggressive tumor growth correlates with short median overall survival (OS) oscillating between 14 and 17 months. The survival rate of patients in a three-year follow up oscillates around 10%. The interaction of the proteins programmed death-1 (PD-1) and programmed cell death ligand (PD-L1) creates an immunoregulatory axis promoting invasion of glioblastoma multiforme cells in the brain tissue. The PD-1 pathway maintains immunological homeostasis and protects against autoimmunity. PD-L1 expression on glioblastoma surface promotes PD-1 receptor activation in microglia, resulting in the negative regulation of T cell responses. Glioblastoma multiforme cells induce PD-L1 secretion by activation of various receptors such as toll like receptor (TLR), epidermal growth factor receptor (EGFR), interferon alpha receptor (IFNAR), interferon-gamma receptor (IFNGR). Binding of the PD-1 ligand to the PD-1 receptor activates the protein tyrosine phosphatase SHP-2, which dephosphorylates Zap 70, and this inhibits T cell proliferation and downregulates lymphocyte cytotoxic activity. Relevant studies demonstrated that the expression of PD-L1 in glioma correlates with WHO grading and could be considered as a tumor biomarker. Studies in preclinical GBM mouse models confirmed the safety and efficiency of monoclonal antibodies targeting the PD-1/PD-L1 axis. Satisfactory results such as significant regression of tumor mass and longer animal survival time were observed. Monoclonal antibodies inhibiting PD-1 and PD-L1 are being tested in clinical trials concerning patients with recurrent glioblastoma multiforme.
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Antígeno B7-H1/metabolismo , Glioblastoma/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Animales , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Proliferación Celular , Receptores ErbB/metabolismo , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/mortalidad , Humanos , Ratones , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/inmunología , Receptor de Interferón alfa y beta/genética , Receptor de Interferón alfa y beta/metabolismo , Receptores de Interferón/genética , Receptores de Interferón/metabolismo , Transducción de Señal , Linfocitos T/inmunología , Receptor de Interferón gammaRESUMEN
Graves' disease (GD) is an autoimmune disease that affects the thyroid. The development of autoimmunity is associated with innate immune responses where the prominent role plays Toll-like receptors (TLRs). The aim of our study was to assess the relationship between the expression levels of TLR-2 and TLR-4 on CD4+ and CD8+ T as well as CD19+ B lymphocytes in patients with GD and selected clinical parameters. The study group consisted of 32 women with GD, the control group consisted of 20 healthy women. Immunophenotyping was performed using the flow cytometry and cytokines concentrations were assessed using ELISA assay. The mean percentage of CD4+/TLR-2+ and CD8+/TLR-2+ T cells in patients with GD was higher than in the control group (p < 0.0001). After obtaining euthyroidism, the mean percentage of CD4+/TLR-2+ T cells in patients with GD decreased (p < 0.0001). The expression level of TLR-2 on CD4+ T lymphocytes correlated with serum FT3 concentration in patients with GD (r = 0.47, p = 0.007). The mean percentage of CD8+/TLR-2+ T cells in patients with GD before treatment compared to patients with GD after obtaining euthyroidism was higher (p = 0.0163). Similar findings were found for TLR-4. Thus the TLR-2 and TLR-4 can be a prognostic marker for Graves' disease.
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Enfermedad de Graves/etiología , Enfermedad de Graves/metabolismo , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismo , Adulto , Linfocitos B/inmunología , Linfocitos B/metabolismo , Biomarcadores , Citocinas/metabolismo , Femenino , Expresión Génica , Humanos , Persona de Mediana Edad , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/genéticaRESUMEN
Graves' disease (GD) it the most common chronic organ-specific thyroid disorder without a fully recognized etiology. The pathogenesis of the disease accounts for an interaction between genetic, environmental, and immunological factors. The most important environmental factors include viral and bacterial infections. The Epstein-Barr virus (EBV) is one of the most common latent human viruses. Literature has suggested its role in the development of certain allergic and autoimmune diseases. EBV also exhibits oncogenic properties. The aim of the study was to analyze and compare the presence of EBV DNA in peripheral blood mononuclear cells (PBMCs) in patients with newly recognized GD and to find a correlation between EBV infection and the clinical picture of GD. The study included 39 untreated patients with newly diagnosed GD and a control group of 20 healthy volunteers who were gender and age matched. EBV DNA was detected with reverse transcription polymerase chain reaction (RT PCR) assay. The studies showed a significantly higher incidence of EBV copies in PBMCs among GD patients compared to the control group. Whereas, no significant correlations were found between the incidence of EBV copies and the evaluated clinical parameters. Our results suggest a probable role of EBV in GD development. EBV infection does not affect the clinical picture of Graves' disease.
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Infecciones por Virus de Epstein-Barr/epidemiología , Enfermedad de Graves/virología , Adulto , Anciano , ADN Viral/sangre , Infecciones por Virus de Epstein-Barr/sangre , Femenino , Enfermedad de Graves/epidemiología , Enfermedad de Graves/etiología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Incidencia , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is defined as a severe, progressive lymphoproliferative disorder associated with active EBV infection persisting longer than 6 months and developing in patients without recognised immunodeficiency. Rarely, interstitial pneumonitis (IP) occurs as a serious complication in CAEBV patients. The standard therapeutic regimen for IP in CAEBV has not yet been defined. Although interferon alpha (IFN-alpha) is known to suppress viral DNA replication by affecting its basal promoter activation process, it is rarely used in CAEBV patients. CASE PRESENTATION: A 22-year-old Caucasian woman, diagnosed with CAEBV 1.5 years earlier, was admitted to the Immunology Clinic due to a 4-week history of productive cough, fever and general weakness. Cultures of blood, urine and sputum were negative, but EBV DNA copies were found in the sputum, whole blood, isolated peripheral blood lymphocytes as well as in the blood plasma. Cytokine assessment in peripheral blood revealed the lack of IFN-alpha synthesis. Disseminated maculate infiltrative areas in both lungs were observed on a computed tomography (CT) chest scan. The patient was not qualified for the allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to the risk of immunosuppression-related complications of infectious IP. Inhaled (1.5 million units 3 times a day) and subcutaneous (6 million units 3 times a week) IFN-alpha was implemented. To the best of our knowledge, this was the first documented use of inhaled IFN-alpha in a patient with CAEBV and concomitant IP. Patient's status has improved, and she was eventually qualified to allo-HSCT with reduced conditioning. Currently, the patient feels well, no EBV was detected and further regression of pulmonary changes was documented. CONCLUSIONS: CAEBV should be considered in patients who present with interstitial lung infiltration and involvement of other organs. Although more promising results have been obtained with allo-HSCT, inhaled IFN-alpha may also be a therapeutic option in patients with CAEBV and a concomitant IP.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedad Crónica , Femenino , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/patogenicidad , Humanos , Enfermedades Pulmonares Intersticiales/virología , Adulto JovenRESUMEN
The cause of endometriosis remains unknown. However, studies investigating the link between this condition and the immune system revealed several immunological abnormalities focused on cell-mediated immunity. As a major immune checkpoint, programmed cell death protein 1 (PD-1) displays an important inhibitory function in the maintenance of peripheral tolerance. The expression of PD-1 and its ligand (PD-L1) may contribute to continuous T cell activation and development of inflammation and injury of the tissue. To our knowledge, this is the first study evaluating frequencies of PD-1-positive T CD3+ cells (CD4+ and CD8+) and B cells (CD19+) in patients with endometriosis. Peripheral blood (PB) samples from 25 female patients and 20 healthy age and sex-matched subjects serving as controls were used in the study. Using flow cytometric analysis, we assessed the differences in the frequencies of PD-1-positive T and B lymphocytes in the study group and healthy individuals. Alteration of the PD-1/PD-L1 axis may contribute to the pathogenesis of endometriosis, as patients with advanced disease are characterized by higher frequencies of PD-1-positive T and B cells. Expression of PD-1 and PD-L1 on T and B cells could represent the hallmark of immune system reaction to chronic antigenic exposition in patients with endometriosis.
Asunto(s)
Endometriosis/metabolismo , Linfocitos/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Antígenos CD19/metabolismo , Linfocitos B/metabolismo , Femenino , Humanos , Activación de Linfocitos/fisiología , MasculinoRESUMEN
Although fungal colonization is implicated in the pathogenesis of psoriasis, its prevalence remains unclear. The aim of this systematic review and meta-analysis was to provide an overview on the prevalence of Candida species in patients with psoriasis. We searched databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and http://clinicaltrials.gov) to identify studies involving subjects of any age with an established diagnosis of psoriasis and healthy controls, who were tested for carriage of Candida spp. on the skin or mucosal membranes (or saliva and stool), or presented with clinical candidiasis with microbiologically confirmed etiology. We identified nine cross-sectional studies including a total of 1038 subjects with psoriasis (psoriatics) and 669 controls. We found Candida species detection rates for psoriatics were significantly higher than those in the controls, especially in the oral mucosa milieux. These results suggest psoriasis may be one of the systemic diseases that predispose to oral Candida spp. carriage and infection.