RESUMEN
Therapeutic apheresis refers to a group of extracorporeal blood processing procedures used in the treatment of a variety of systemic diseases. These complex procedures are burdened by adverse reactions related to both procedures and underlying medical conditions. Given the importance of centralizing the collection and the analysis of information on therapeutic apheresis, the Italian National Blood Center (NBC), at the request of the Italian Scientific Society of Hemapheresis and Cell Manipulation (SIdEM), implemented the Italian Registry of Therapeutic Apheresis (IRTA) including it in the Information System of Transfusion Services (SISTRA), coordinated by the NBC. In 2022, a total of 34,702 therapeutic apheresis procedures was carried out in 8,781 patients, including paediatric patients, with an average of 3.9 procedures per patient. The 2022 IRTA data indicate that the patient with hematological and/or neurological disorders mainly turns to the apheresis centers. These results confirm the IRTA data from years 2020 and 2021. In the hematological field, the apheresis centers supply hematopoietic stem cells collection for autologous transplantation as well as mononuclear cell collection for extracorporeal photopheresis. With regard to the neurological field, myasthenia, chronic inflammatory demyelinating polyneuropathy and Guillain-Barré syndrome along with other neurological pathologies related to immune disorders are the most treated. In conclusion, this manuscript presents 2022 activity data of IRTA providing institutions and scientific societies with a wide range of information including type and number of therapeutic procedures, adverse events and patients' outcome.
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Eliminación de Componentes Sanguíneos , Fotoféresis , Humanos , Niño , Eliminación de Componentes Sanguíneos/métodos , Sistema de Registros , Trasplante Autólogo , ItaliaRESUMEN
In 2019, the Italian National Blood Center (NBC), at the request of the Italian Scientific Society of Haemapheresis and Cell Manipulation (SIdEM), included the Italian Registry of Therapeutic Apheresis (IRTA) in the Information System of Transfusion Services (SISTRA), whose activity is coordinated by the NBC. The IRTA provides institutions and scientific societies with a wide range of information including therapeutic procedures and outcomes of treated patients. The Italian National Health Service offers therapeutic apheresis for patients with various conditions, but it is mainly the patient with haematological and/or neurological disorders who turns to the apheresis centres as evidenced by the activity data of 2021. In the haematological field, the apheresis centres mainly supply haematopoietic stem cells for autologous or allogeneic transplantation as well as mononuclear cell collection for extracorporeal photopheresis (ECP), a therapeutic approach of II line in post-transplant Graft versus Host Disease. The activity of 2021 in the neurological field confirms the data of 2019, the pre-pandemic year, and indicates that myasthenia, chronic inflammatory demyelinating polyneuropathy and Guillain-Barré syndrome along with other neurological pathologies related to immune disorders are the diseases in which apheresis procedures are most used. In conclusion, the IRTA is a valuable tool for monitoring the activity of apheresis centres carried out at a national level and above all for providing an overall picture of how the use of this therapeutic tool evolves and changes over time.
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Eliminación de Componentes Sanguíneos , Enfermedad Injerto contra Huésped , Fotoféresis , Humanos , Medicina Estatal , Eliminación de Componentes Sanguíneos/métodos , Sistema de Registros , Italia , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) caused outbreaks of the pandemic starting from the end of 2019 and, despite ongoing vaccination campaigns, still influences health services and economic factors globally. Understanding immune protection elicited by natural infection is of critical importance for public health policy. This knowledge is instrumental to set scientific parameters for the release of "immunity pass" adopted with different criteria across Europe and other countries and to provide guidelines for the vaccination of COVID-19 recovered patients. Here, we characterized the humoral response triggered by SARS-CoV-2 natural infection by analyzing serum samples from 94 COVID-19 convalescent patients with three serological platforms, including live virus neutralization, pseudovirus neutralization, and ELISA. We found that neutralization potency varies greatly across individuals, is significantly higher in severe patients compared with mild ones, and correlates with both Spike and receptor-binding domain (RBD) recognition. We also show that RBD-targeting antibodies consistently represent only a modest proportion of Spike-specific IgG, suggesting broad specificity of the humoral response in naturally infected individuals. Collectively, this study contributes to the characterization of the humoral immune response in the context of natural SARS-CoV-2 infection, highlighting its variability in terms of neutralization activity, with implications for immune protection in COVID-19 recovered patients.
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Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Dominios Proteicos/inmunología , SARS-CoV-2/inmunología , Adulto , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/prevención & control , Línea Celular , Chlorocebus aethiops , Convalecencia , Ensayo de Inmunoadsorción Enzimática , Europa (Continente) , Femenino , Células HEK293 , Humanos , Inmunidad Humoral/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Glicoproteína de la Espiga del Coronavirus/inmunología , Células Vero , Adulto JovenRESUMEN
OBJECTIVES AND BACKGROUND: Convalescent plasma (CP) has been used worldwide to contrast SARS-CoV-2 infection. Since April 2020, it has also been used in the treatment of patients with COVID-19 in the Veneto region (Italy), along with all the other available drugs and therapeutic tools. Here we report data analysis and clinical results in 1,517 COVID-19 inpatients treated with CP containing high-titre neutralizing anti-SARS-CoV-2 antibodies (CCP). Mortality after 30 days of hospitalization has been considered primary outcome, by comparing patients treated with CCP vs all COVID-19 patients admitted to hospitals of the Veneto region in a one-year period (from April 2020 to April 2021). PATIENTS AND METHODS: Adult inpatients with a severe form of COVID-19 have been enrolled, with at least one of the following inclusion criteria: 1) tachypnea with respiratory rate (RR) ≥ 30 breaths/min; 2) oxygen saturation (SpO2) ≤ 93% at rest and in room air; 3) partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤ 200 mmHg, 4) radiological picture and/or chest CT scan showing signs of interstitial disease and/or rapid progression of lung involvement. Patients received a maximum of three therapeutic fractions (TFs) of CCP with a neutralizing antibody titre of ≥ 1:160, administered over a period of 3-5 days. If TFs of CCP with titre ≥ 1:160 were unavailable, 2 with antibody titre of ≥ 1:80 have been administered. RESULTS: Of the 1,517 patients treated with CCP, 209 deceased at the 30-day follow-up (14%). Death was significantly associated with an older age (p<0.001), a longer time of hospitalization before CCP infusion (p<0.001), a greater number of inclusion criteria (p<0.001) and associated comorbidities (p<0.001). Conditions significantly associated with an increased frequency of death were PaO2/FiO2 ≤ 200 (p<0.001) and tachypnea with RR>30 (p<0.05) at entry, concurrent arterial hypertension (p<0.001), cardiovascular disease (p<0.001), chronic kidney disease (p<0.001), dyslipidemia (p<0.05) and cancer (p<0.05). Moreover, factors leading to an unfavorable prognosis were a life-threatening disease (p<0.001), admission to Intensive Care Unit (p<0.001), high flow oxygen therapy or mechanical ventilation (p<0.05) and a chest X-ray showing consolidation area (p<0.001). By analyzing the regional report of hospitalized patients, a comparison of mortality by age group, with respect to our series of patients treated with CCP, has been made. Mortality was altogether lower in patients treated with CCP (14% v. 25%), especially in the group of the elderly patients (23% vs 40%,), with a strong significance (p<0.001). As regards the safety of CCP administration, 16 adverse events were recorded out of a total of 3,937 transfused TFs (0,4%). CONCLUSIONS: To overcome the difficulties of setting up a randomized controlled study in an emergency period, a data collection from a large series of patients with severe COVID-19 admitted to CCP therapy with well-defined inclusion criteria has been implemented in the Veneto region. Our results have shown that in patients with severe COVID-19 early treatment with CCP might contribute to a favourable outcome, with a reduced mortality, in absence of relevant adverse events.
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COVID-19 , SARS-CoV-2 , Adulto , Anciano , COVID-19/terapia , Humanos , Inmunización Pasiva , Pacientes Internos , Sistema de Registros , Resultado del Tratamiento , Sueroterapia para COVID-19RESUMEN
The National Blood Centre (NBC) at the request of the Italian Scientific Society of Haemapheresis and Cell Manipulation (SIdEM) has funded and developed a software dedicated to the collection of data related to therapeutic apheresis procedures, known as the Italian Registry of Therapeutic Apheresis (IRTA). Although on a voluntary basis, participation in the registry was widespread. The data collected includes type and number of procedures, patients treated and their outcomes, and reported adverse events to the procedures. For the years 2019 and 2020, the therapeutic apheresis procedure was widely used in the field of haematology, transplantation and rheumatology and was mainly associated with mild adverse events, thus showing a high level of safety. In addition to allowing the competent institution to monitor an important activity in the transfusion medicine field, the Registry is a new starting point for collaboration between transfusion centres distributed throughout the national territory and could encourage the design of major clinical trials.
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Eliminación de Componentes Sanguíneos/métodos , Transfusión Sanguínea/métodos , Humanos , Italia , Sistema de RegistrosRESUMEN
The psychosocial consequences of the COVID-19 pandemic caused multifaceted challenges in clinical and therapeutic practices. This was the case at the Therapeutic Apheresis Unit of the Padua University Hospital too. Several published reports describe the increase in alcohol and food addiction diseases. In this context, during the last months, the Padua Therapeutic Apheresis Unit treated many more patients with acute pancreatitis due to severe hypertriglyceridemia with therapeutic plasma exchange than in the previous ten years. Furthermore, retrospective cohort studies have been recently published describing the onset of acute pancreatitis during the COVID-19 infection even if, to date, there is still insufficient evidence to estabilish a direct causality. Anyway, the COVID-19 pandemic translated into changes of the overall disease prevalence scenario and therefore the Padua Therapeutic Apheresis Unit will need to reorganise its Therapeutic Apheresis activity.
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Hipertrigliceridemia/complicaciones , Pancreatitis/etiología , Pancreatitis/fisiopatología , Pancreatitis/terapia , Intercambio Plasmático/métodos , Adulto , COVID-19 , Femenino , Humanos , Hipertrigliceridemia/fisiopatología , Masculino , Persona de Mediana Edad , SARS-CoV-2RESUMEN
BACKGROUND: Convalescent plasma (CP) has been used in the past in various pandemics, in particular in H1N1, SARS and MERS infections. In Spring 2020, when ongoing the SARS-CoV-2 pandemics, the Veneto Region (V-R) has proposed setting-up an anti-SARS-CoV-2 CP (CCP) Bank, with the aim of preparing a supply of CCP immediately available in case of subsequest epidemic waves. MATERIALS AND METHODS: Key-points to be developed for a quick set-up of the V-R CCP Bank have been recruitment of donors recovered from COVID-19 infection, laboratory analysis for the biological qualification of the CCP units, including titre of neutralizing antibodies and reduction of pathogens, according to National Blood Centre (CNS) Directives, adaptation of the V-R Information Technology systems and cost analysis. Some activities, including diagnostic and viral inactivation processes, have been centralized in 2 or 3 sites. Laboratory analysis upon preliminary admission of the donor included all tests required by the Italian laws and the CNS directives. RESULTS: From April to August 2020, 3,298 people have contacted the V-R Blood Transfusion Services: of these, 1,632 have been evaluated and examined as first time donors and those found to be suitable have carried out 955 donations, from which 2,626 therapeutic fractions have been obtained, at a cost around 215,00 Euro. Since October 2020, the number of COVID-19 inpatients has had a surge with a heavy hospital overload. Moreover, the high request of CCP therapy by clinicians has been just as unexpected, showing a wide therapeutic use. CONCLUSIONS: The organizational model here presented, which has allowed the rapid collection of a large amount of CCP, could be useful when facing new pandemic outbreaks, especially in low and middle income countries, with generally acceptable costs.
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Bancos de Sangre/organización & administración , COVID-19/terapia , Defensa Civil/organización & administración , Pandemias , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Bancos de Sangre/economía , Donantes de Sangre , Seguridad de la Sangre/métodos , Infecciones de Transmisión Sanguínea/prevención & control , Costos y Análisis de Costo , Selección de Donante/legislación & jurisprudencia , Humanos , Inmunización Pasiva/estadística & datos numéricos , Italia , Modelos Organizacionales , Plasma , SARS-CoV-2/inmunología , Inactivación de Virus , Sueroterapia para COVID-19RESUMEN
Mosquitoes of the Aedes genus transmit arboviruses of great importance to human health as dengue, chikungunya, Zika and yellow fever. The tiger mosquito Aedes albopictus can play an important role as arboviral vector, especially when Aedes aegypti is absent or present at low levels. Remarkably, the rapid worldwide spreading of the tiger mosquito is expanding the risk of arboviral transmission also to temperate areas, and the autochthonous cases of chikungunya, dengue and Zika in Europe emphasize the need for improved monitoring and control. Proteomic and transcriptomic studies on blood feeding arthropod salivary proteins paved the way toward the exploitation of genus-specific mosquito salivary proteins for the development of novel tools to evaluate human exposure to mosquito bites. We previously found that the culicine-specific 34k2 salivary protein from Ae. albopictus (al34k2) evokes specific IgG responses in experimentally exposed mice, and provided preliminary evidence of its immunogenicity to humans. In this study we measured IgG responses to al34k2 and to Ae. albopictus salivary gland protein extracts (SGE) in individuals naturally exposed to the tiger mosquito. Sera were collected in two areas of Northeast Italy (Padova and Belluno) during two different time periods: at the end of the low- and shortly after the high-density mosquito seasons. Anti-SGE and anti-al34k2 IgG levels increased after the summer period of exposure to mosquito bites and were higher in Padova as compared to Belluno. An age-dependent decrease of anti-saliva IgG responses was found especially in Padova, an area with at least 25 years history of Ae. albopictus colonization. Moreover, a weak correlation between anti-saliva IgG levels and individual perception of mosquito bites by study participants was found. Finally, determination of anti-al34k2 IgG1 and IgG4 levels indicated a large predominance of IgG1 antibodies. Overall, this study provides a convincing indication that antibody responses to al34k2 may be regarded as a reliable candidate marker to detect temporal and/or spatial variation of human exposure to Ae. albopictus; a serological tool of this kind may prove useful both for epidemiological studies and to estimate the effectiveness of anti-vectorial measures.
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Aedes , Infección por el Virus Zika , Virus Zika , Animales , Formación de Anticuerpos , Europa (Continente) , Humanos , Inmunoglobulina G , Italia , Ratones , Mosquitos Vectores , Proteómica , Proteínas y Péptidos SalivalesRESUMEN
Passive immunotherapy with plasma derived from patients convalescent from SARS-CoV-2 infection can be a promising approach in the treatment of COVID-19 patients. It is important that Blood Establishments are prepared to satisfy requests for immune plasma by defining the requirements applicable to plasma donors and the standards for preparation, qualification, storage, distribution and control of use of the product. This position paper is aimed to give recommendations on biological characteristics of a plasma preparation from convalescent donors and to support the evaluation of this therapeutic approach in more rigorous investigations.
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Betacoronavirus/inmunología , Infecciones por Coronavirus/terapia , Inmunización Pasiva , Neumonía Viral/terapia , Anticuerpos Antivirales/sangre , Eliminación de Componentes Sanguíneos/métodos , Donantes de Sangre , COVID-19 , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/inmunología , Selección de Donante/normas , Humanos , Sueros Inmunes/efectos adversos , Sueros Inmunes/aislamiento & purificación , Inmunización Pasiva/efectos adversos , Inmunización Pasiva/métodos , Pandemias , Neumonía Viral/sangre , Neumonía Viral/inmunología , Etiquetado de Productos , Riesgo , SARS-CoV-2 , Sueroterapia para COVID-19RESUMEN
Passive immunotherapy with plasma derived from convalescent patients recovering from SARS-CoV-2 infection can be a promising approach in the treatment of COVID-19 patients. It is important that blood establishments are ready to satisfy requests for immune plasma by defining the requirements applicable to plasma donors and the standards for preparation, qualification, storage, distribution, and control of product use. This Position paper aims to give recommendations on the biological characteristics of a plasma preparation from convalescent donors and to support the evaluation of this therapeutic approach in more rigorous investigations.
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Anticuerpos Antivirales/uso terapéutico , Betacoronavirus/inmunología , Infecciones por Coronavirus/terapia , Inmunización Pasiva/métodos , Plasma/inmunología , Neumonía Viral/terapia , Anticuerpos Antivirales/efectos adversos , Bancos de Sangre/organización & administración , Bancos de Sangre/normas , Donantes de Sangre/legislación & jurisprudencia , COVID-19 , Europa (Continente) , Humanos , Esquemas de Inmunización , Inmunización Pasiva/efectos adversos , Inmunización Pasiva/normas , Consentimiento Informado , Italia , Pandemias , SARS-CoV-2 , Sueroterapia para COVID-19RESUMEN
Introduction. Parathyroid hormone (PTH) is a linear peptide constituted by 84 amino acids and active in its 1-84 form, but a wide range of PTH forms produced by its post-transcriptional modifications are present in blood. Many assays with different specificities are commercially available. The aim of our study was to compare a 2nd and 3rd generation in healthy population in order to better define the reference range in the healthy population residing in our region. Materials and Methods. 108 subjects (53 females and 55 males) referring to the transfusion donor were enrolled in the study centre in April 2016 and underwent PTH levels measurements with a 3rd generation kit (chemiluminescent immunoassay DiaSorin Liaison) and with a 2nd generation kit (immunoradiometric assay Total Intact PTH Assay (Coated Tube), Scantibodies). Also calcium, phosphate, creatinine, and 25OHD3 were measured. A questionnaire on lifestyle and dietary habits was obtained. RESULTS: The median PTH values obtained with the 2nd generation assay and the whole 3rd generation assay were 20.26 pg/ml and 23.11 pg/ml, respectively. Bland-Altman method showed substantial concordance between the two PTH assays, although with an overestimation of the 3rd generation method over the 2nd generation method. There was no correlation between 3rd generation PTH and 25OHD3 and creatinine. Calcium was negatively correlated with PTH only when measured with 3rd generation kit. CONCLUSIONS: On the basis of our data, obtained from healthy subjects, we can conclude that the reference range used by our laboratory was too narrow and was necessary to reestablish normal ranges according to our population. This is useful to avoid hyperparathyroidism misdiagnosis.
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INTRODUCTION: Therapeutic apheresis (TA) represents a treatment option for pre-existing conditions or diseases occurring during gestation. Although pregnancy is not a contraindication per se, due to the lack of evidence-based guidelines and presumed risk of maternal/fetal adverse events there is a general resistance to its application. MATERIAL AND METHODS: Between January 2005 and August 2017, at the Apheresis Unit of the University Hospital of Padua 936 TA procedures were performed during 57 pregnancies in 48 patients: 813 Plasma Exchange sessions, 119 Immunoadsorptions, 4 Red Blood Cell exchanges. The treated disease were as follows: antiphospholipid syndrome (18 patients), autoimmune congenital heart block (18), myasthenia gravis (3), Rh alloimmunization (2), systemic sclerosis (1), suspected autoimmune encephalitis (1), severe hypertriglyceridaemia (1), post partum hemolytic-uremic syndrome (1), sickle cell disease (1), lupus nephritis (1) and thrombotic thrombocytopenic purpura (1). RESULTS: In the time period considered the apheresis sessions applied to pregnant women were 7.1% of the total (nâ¯=â¯13.251). The median age at the first treatment was 33 years. The median week of gestation (WG) at the beginning of treatments was 21. Twenty (2.1%) sessions were complicated by adverse events, none requiring or prolonging hospitalization. There were 50 live births, 5 spontaneous abortions and 2 voluntary terminations of pregnancy. Median WG at delivery was 35 and caesarean section was performed in 46 cases. CONCLUSIONS: Our data showed that TA in pregnancy is well tolerated. Close collaboration between clinician, obstetrician and TA specialist is crucial to ensure a good outcome of high-risk pregnancies.
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Intercambio Plasmático , Complicaciones del Embarazo/terapia , Resultado del Embarazo , Adulto , Femenino , Humanos , Embarazo , Complicaciones del Embarazo/sangre , Estudios RetrospectivosRESUMEN
The priority objectives of the Italian Transfusion System are self-sufficiency for blood components and for plasma-derived products. Currently the collection activity guarantees self-sufficiency of blood components, including plasma for clinical use, but not for plasma-derived drugs, ie albumin and immunoglobulins in particular. The National Plasma Program of 2016-2020, issued a Ministerial Decree on December, 2, 2016, aims to achieve this goal, both by increasing the collection of plasma and therefore its transfer to plasma derivation companies, and by increasing the appropriateness of the requests. Currently, the companies Grifols SpA, Kedrion SpA, CSL Behring, and Baxter-Baxalta Srl are present on the Italian market, individually or in business associations, with which the various Italian regions have established an agreement based on the national legislation.
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Transfusión de Componentes Sanguíneos , Plasma , Humanos , ItaliaRESUMEN
The medieval history of several populations often suffers from scarcity of contemporary records resulting in contradictory and sometimes biased interpretations by historians. This is the situation with the population of the island of Crete, which remained relatively undisturbed until the Middle Ages when multiple wars, invasions, and occupations by foreigners took place. Historians have considered the effects of the occupation of Crete by the Arabs (in the 9th and 10th centuries C.E.) and the Venetians (in the 13th to the 17th centuries C.E.) to the local population. To obtain insights on such effects from a genetic perspective, we studied representative samples from 17 Cretan districts using the Illumina 1 million or 2.5 million arrays and compared the Cretans to the populations of origin of the medieval conquerors and settlers. Highlights of our findings include (1) small genetic contributions from the Arab occupation to the extant Cretan population, (2) low genetic contribution of the Venetians to the extant Cretan population, and (3) evidence of a genetic relationship among the Cretans and Central, Northern, and Eastern Europeans, which could be explained by the settlement in the island of northern origin tribes during the medieval period. Our results show how the interaction between genetics and the historical record can help shed light on the historical record.
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Genética de Población , Población Blanca/genética , Cruzamientos Genéticos , Bases de Datos Genéticas , Etnicidad/genética , Variación Genética , Genética de Población/historia , Genoma Humano , Genómica/métodos , Genotipo , Geografía , Grecia , Historia Medieval , Migración Humana , Humanos , Población Blanca/historiaRESUMEN
In Italy therapeutic apheresis procedures were carried out for the first time in the '70s. in the '80s the Italian Society of Hemapheresis was founded, formerly named SIDE, now SIdEM (Italian Society of Hemapheresis and Cellular Manipulation). From the beginning, the collection and the analysis of activity data have been seen as a way to improve the knowledge on mechanisms of action, to identify the correct rationale in order to intervene in the most appropriate clinical indications. Over the years the data collection has been refreshed and today we can rely on information representing the evolution of TA in Italy, from an organizational/technological viewpoint and according to clinical indications. Over the years the aspects that have mainly changed are the technologies, the organizational and managerial aspects and, above all, the clinical indications. The primary indication for therapeutic apheresis is still today the thrombotic thrombocytopenic purpura, but corrently, whenever a disease recognizes an autoimmune pathogenesis, the use of apheresis may be a valid therapeutic tool in the event of failure or partial efficacy of conventional drug therapy. The continuous monitoring of apheresis activity through Registries is a useful tool to follow the evolution of the apheresis practice.
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Eliminación de Componentes Sanguíneos , Sistema de Registros , Eliminación de Componentes Sanguíneos/historia , Eliminación de Componentes Sanguíneos/métodos , Historia del Siglo XX , Historia del Siglo XXI , Humanos , ItaliaRESUMEN
BACKGROUND: Alteration of T-follicular helper (TFH) and regulatory (TFR) subpopulations may contribute to the development of auto-reactive B-cell. OBJECTIVE: To investigate whether changes in TFH and TFR subsets are associated with abnormal IgG synthesis in blood and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. METHODS: Paired blood and CSF samples were obtained from 31 untreated relapsing-remitting multiple sclerosis (RRMS) patients at diagnosis. Peripheral blood TFH (CD3+CD4+CXCR5+CD25-CD127+), TFR (CD3+CD4+CXCR5+CD25+CD127dim), conventional T-Helper (TH, CD3+CD4+CXCR5-CD25-CD127+), and regulatory T-cells (T-Reg, CD3+CD4+CXCR5-CD25+CD127dim) were analyzed in all RRMS patients and in 13 healthy controls (HCs). Qualitative and quantitative intrathecal IgG synthesis was evaluated in RRMS patients, who were then further subclassified according to the presence of IgG oligoclonal bands in blood and/or CSF. RESULTS: Compared to HC, RRMS had lower TFR percentage ( p < 0.01) and higher TFH/TFR ratio ( p < 0.001). In RRMS, TFH/TFR ratio correlated with both qualitative ( r = 0.56, p < 0.005) and quantitative intrathecal IgG synthesis (IgG Index: r = 0.78; IgGLoc: r = 0.79; IgGIF: r = 0.76, all p < 0.001). Patients with the highest TFH/TFR ratios had higher percentages of circulating B-cells (36.1 ± 35.2%, p < 0.05). CONCLUSION: In RRMS, increased TFH/TFR ratio associates with abnormal IgG production in blood and CSF, suggesting that antibody-producing cells, derived from deregulated peripheral germinal center reaction, colonize the CNS.