Person: Sánchez Ramón, Silvia María
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First Name
Silvia María
Last Name
Sánchez Ramón
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Inmunología, Oftalmología y ORL
Area
Inmunología
Identifiers
11 results
Search Results
Now showing 1 - 10 of 11
- Project number: PIMCD118/23-24
Item El podcast como herramienta de innovación docente: “reumatología para estudiantes de medicina”(2024) Gómez Martínez, Ana María; Toledano Martínez, María Esther; Candelas Rodríguez, Gloria Del Mar; Montilla Morales, Carlos A.; Sánchez Ramón, Silvia María; Calatayud Gastardi, Joaquín Item Specific Cellular and Humoral Immune Responses to the Neoantigen RBD of SARS-CoV-2 in Patients with Primary and Secondary Immunodeficiency and Healthy Donors(Biomedicines, 2023) Mohamed, Kauzar Mohamed; Guevara Hoyer, Kissy; Jiménez García, Carlos; García Bravo, Laura; Rodríguez de la Peña, Antonia; Mediero Valeros, Beatriz; Cañizares Velázquez, Cristina; Culebras López, Esther; Cabello, Noemí; Estrada Pérez, Vicente; Fernández Arquero, Miguel; Ocaña, Alberto; Delgado-Iribarren García-Campero, Albert; Martínez-Novillo González, Mercedes; Bolaños, Estefanía; Anguita Mandly, Eduardo Luis; Peña Cortijo, Ascensión; Benavente Cuesta, Celina; Benítez Fuentes, Javier David; Pérez Segura, Pedro; Sánchez Ramón, Silvia MaríaPatients with antibody deficiency disorders, such as primary immunodeficiency (PID) or secondary immunodeficiency (SID) to B-cell lymphoproliferative disorder (B-CLPD), are two groups vulnerable to developing the severe or chronic form of coronavirus disease caused by SARS-CoV-2 (COVID-19). The data on adaptive immune responses against SARS-CoV-2 are well described in healthy donors, but still limited in patients with antibody deficiency of a different cause. Herein, we analyzed spike-specific IFN-γ and anti-spike IgG antibody responses at 3 to 6 months after exposure to SARS-CoV-2 derived from vaccination and/or infection in two cohorts of immunodeficient patients (PID vs. SID) compared to healthy controls (HCs). Pre-vaccine anti-SARS-CoV-2 cellular responses before vaccine administration were measured in 10 PID patients. Baseline cellular responses were detectable in 4 out of 10 PID patients who had COVID-19 prior to vaccination, perceiving an increase in cellular responses after two-dose vaccination (p < 0.001). Adequate specific cellular responses were observed in 18 out of 20 (90%) PID patients, in 14 out of 20 (70%) SID patients and in 74 out of 81 (96%) HCs after vaccination (and natural infection in some cases). Specific IFN-γ response was significantly higher in HC with respect to PID (1908.5 mUI/mL vs. 1694.1 mUI/mL; p = 0.005). Whereas all SID and HC patients mounted a specific humoral immune response, only 80% of PID patients showed positive anti-SARS-CoV-2 IgG. The titer of anti-SARS-CoV-2 IgG was significantly lower in SID compared with HC patients (p = 0.040), without significant differences between PID and HC patients (p = 0.123) and between PID and SID patients (p =0.683). High proportions of PID and SID patients showed adequate specific cellular responses to receptor binding domain (RBD) neoantigen, with a divergence between the two arms of the adaptive immune response in PID and SID patients. We also focused on the correlation of protection of positive SARS-CoV-2 cellular response to omicron exposure: 27 out of 81 (33.3%) HCs referred COVID-19 detected by PCR or antigen test, 24 with a mild course, 1 with moderate symptoms and the remaining 2 with bilateral pneumonia that were treated in an outpatient basis. Our results might support the relevance of these immunological studies to determine the correlation of protection with severe disease and for deciding the need for additional boosters on a personalized basis. Follow-up studies are required to evaluate the duration and variability in the immune response to COVID-19 vaccination or infection.Item A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections(Frontiers in Immunology, 2021) Martín De La Cruz, Leticia; Sevilla Ortega, Carmen ; Benito Villalvilla, Cristina; Díez Rivero, Carmen; Sánchez Ramón, Silvia María; Subiza Garrido-Lestache, José Luis; Palomares Gracia, ÓscarRecurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems with high socio-economic impact worldwide. Antibiotic and antifungal prophylaxis remain the gold standard treatments for RUTIs and RVVCs, contributing to the massive rise of antimicrobial resistance, microbiota alterations and co-infections. Therefore, the development of novel vaccine strategies for these infections are sorely needed. The sublingual heat-inactivated polyvalent bacterial vaccine MV140 shows clinical efficacy for the prevention of RUTIs and promotes Th1/Th17 and IL-10 immune responses. V132 is a sublingual preparation of heat-inactivated Candida albicans developed against RVVCs. A vaccine formulation combining both MV140 and V132 might well represent a suitable approach for concomitant genitourinary tract infections (GUTIs), but detailed mechanistic preclinical studies are still needed. Herein, we showed that the combination of MV140 and V132 imprints human dendritic cells (DCs) with the capacity to polarize potent IFN-γ– and IL-17A–producing T cells and FOXP3+ regulatory T (Treg) cells. MV140/V132 activates mitogen-activated protein kinases (MAPK)-, nuclear factor-κB (NF-κB)- and mammalian target of rapamycin (mTOR)-mediated signaling pathways in human DCs. MV140/V132 also promotes metabolic and epigenetic reprogramming in human DCs, which are key molecular mechanisms involved in the induction of innate trained immunity. Splenocytes from mice sublingually immunized with MV140/V132 display enhanced proliferative responses of CD4+ T cells not only upon in vitro stimulation with the related antigens contained in the vaccine formulation but also upon stimulation with phytohaemagglutinin. Additionally, in vivo sublingual immunization with MV140/V132 induces the generation of IgG and IgA antibodies against all the components contained in the vaccine formulation. We uncover immunological mechanisms underlying the potential mode of action of a combination of MV140 and V132 as a novel promising trained immunity-based vaccine (TIbV) for GUTIs.Item Inherited human ezrin deficiency impairs adaptive immunity(Journal of Allergy and Clinical Immunology, 2023) García-Solís, Blanca et al.; Rebeca Pérez de Diego; Martínez Martínez, Laura María; Recio Hoyas, María José; Fernández Arquero, Miguel; Sánchez Ramón, Silvia MaríaBackground Inborn errors of immunity (IEI) are a group of monogenic diseases that confer susceptibility to infection, autoimmunity, and cancer. Despite the life-threatening consequences of some IEI, their genetic cause remains unknown in many patients. Objective We investigated a patient with an IEI of unknown genetic etiology. Methods Whole-exome sequencing identified a homozygous missense mutation of the gene encoding ezrin (EZR), substituting a threonine for an alanine at position 129. Results Ezrin is one of the subunits of the ezrin, radixin, and moesin (ERM) complex. The ERM complex links the plasma membrane to the cytoskeleton and is crucial for the assembly of an efficient immune response. The A129T mutation abolishes basal phosphorylation and decreases calcium signaling, leading to complete loss of function. Consistent with the pleiotropic function of ezrin in myriad immune cells, multidimensional immunophenotyping by mass and flow cytometry revealed that in addition to hypogammaglobulinemia, the patient had low frequencies of switched memory B cells, CD4+ and CD8+ T cells, MAIT, γδ T cells, and centralnaive CD4+ cells. Conclusions Autosomal-recessive human ezrin deficiency is a newly recognized genetic cause of B-cell deficiency affecting cellular and humoral immunity.Item Cost-minimization analysis of immunoglobulin treatment of primary immunodeficiency diseases in Spain(The European Journal of Health Economics, 2021) Alsina, Laia; Montoro, J. Bruno; Moral, Pedro Moral; Neth, Olaf; Ortiz Pica, Marta; Sánchez Ramón, Silvia María; Presa, María; Oyagüez, Itziar; Casado, Miguel Ángel; González Granado, Luis IgnacioPrimary immunodefciency diseases (PID), which are comprised of over 400 genetic disorders, occur when a component of the immune system is diminished or dysfunctional. Patients with PID who require immunoglobulin (IG) replacement therapy receive intravenous IG (IVIG) or subcutaneous IG (SCIG), each of which provides equivalent efcacy. We developed a costminimization model to evaluate costs of IVIG versus SCIG from the Spanish National Healthcare System perspective. The base case modeled the annual cost per patient of IVIG and SCIG for the mean doses (per current expert clinical practice) over 1 year in terms of direct (drug and administration) and indirect (lost productivity for adults and parents/guardians of pediatric patients) costs. It was assumed that all IVIG infusions were administered in a day hospital, and 95% of SCIG infusions were administered at home. Drug costs were calculated from ex-factory prices obtained from local databases minus the mandatory deduction. Costs were valued on 2018 euros. The annual modeled costs were €4,266 lower for patients with PID who received SCIG (total €14,466) compared with those who received IVIG (total €18,732). The two largest contributors were diferences in annual IG costs as a function of dosage (– €1,927) and hospital administration costs (– €2,688). However, SCIG incurred training costs for home administration (€695). Sensitivity analyses for two dose-rounding scenarios were consistent with the base case. Our model suggests that SCIG may be a cost-saving alternative to IVIG for patients with PID in Spain.Item Combined Immune Defect in B-Cell Lymphoproliferative Disorders Is Associated with Severe Infection and Cancer Progression(Biomedicines, 2022) Ochoa Grullón, Juliana Lucía; Guevara Hoyer, Kissy; Pérez López, Cristina; Pérez de Diego, Rebeca; Peña Cortijo, Ascensión; Polo, Marta; Mateo Morales, Marta; Anguita Mandley, Eduardo; Jiménez García, Carlos; Bolaños, Estefanía; Íñigo, Belén; Medina, Fiorella; Rodríguez de la Peña, Antonia; Izquierdo Delgado, Carmen; Fuente Muñoz, Eduardo de la; Mayol, Elsa; Fernandez Arquero, Miguel; González Fernández, Ataúlfo; Benavente Cuesta, Celina; Sánchez Ramón, Silvia MaríaB cell chronic lymphoproliferative diseases (B-CLPD) are associated with secondary antibody deficiency and other innate and adaptive immune defects, whose impact on infectious risk has not been systematically addressed. We performed an immunological analysis of a cohort of 83 B-CLPD patients with recurrent and/or severe infections to ascertain the clinical relevance of the immune deficiency expression. B-cell defects were present in all patients. Patients with combined immune defect had a 3.69-fold higher risk for severe infection (p = 0.001) than those with predominantly antibody defect. Interestingly, by Kaplan–Meier analysis, combined immune defect showed an earlier progression of cancer with a hazard ratio of 3.21, than predominantly antibody defect (p = 0.005). When B-CLPD were classified in low-degree, high-degree, and plasma cell dyscrasias, risk of severe disease and cancer progression significantly diverged in combined immune defect, compared with predominantly antibody defect (p = 0.001). Remarkably, an underlying primary immunodeficiency (PID) was suspected in 12 patients (14%), due to prior history of infections, autoimmune and granulomatous conditions, atypical or variegated course and compatible biological data. This first proposed SID classification might have relevant clinical implications, in terms of predicting severe infections and cancer progression, and might be applied to different B-CLPD entities.Item Unveiling the value of C-reactive Protein as a Severity Biomarker and the IL4/IL13 Pathway as a Therapeutic Target in Recessive Dystrophic Epidermolysis Bullosa: a multiparametric cross-sectional study(Experimental Dermatology, 2024) Quintana Castanedo, Lucía; Sánchez Ramón, Silvia María; Illera, Nuria; Zuluaga Arias, María Del Pilar; Martínez Santamaría, Lucía; Fernández Arquero, Miguel; Río, Marcela del; Vicente López, María Ángeles; Escámez, María José; Sacedón Ayuso, RosaPatients with recessive dystrophic epidermolysis bullosa (RDEB) experience numerous complications, which are exacerbated by inflammatory dysregulation and infection. Understanding the immunological mechanisms is crucial for selecting medications that balance inflammation control and immunocompetence. In this cross-sectional study, aiming to identify potential immunotherapeutic targets and inflammatory biomarkers, we delved into the interrelationship between clinical severity and systemic inflammatory parameters in a representative RDEB cohort. Encompassing 84 patients aged 1 to 67 and spanning all three Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) severity categories, we analyzed the interrelationship of infection history, standard inflammatory markers, systemic cytokines, and Ig levels to elucidate their roles in RDEB pathophysiology. Our findings identify C-reactive protein as an excellent biomarker for disease severity in RDEB. A Type 2 inflammatory profile prevails among moderate and severe RDEB patients, correlating with dysregulated circulating IgA and IgG. These results underscore the IL4/IL13 pathways as potential evidence-based therapeutic targets. Moreover, the complete inflammatory scenario aligns with Staphylococcus aureus virulence mechanisms. Concurrently, abnormalities in IgG, IgE, and IgM levels suggest an immunodeficiency state in a substantial number of the cohort's patients. Our results provide new insights into the interplay of infection and immunological factors in the pathogenesis of RDEB.Item Clinical and Immunological Features of Human BCL10 Deficiency(Frontiers in Immunologý, 2021) Garcia Solis, Blanca; Allende Martínez, Luis Miguel; Fernández Arquero, Miguel; Sánchez Ramón, Silvia María; Recio Hoyas, María José; Pérez de Diego, RebecaThe CARD-BCL10-MALT1 (CBM) complex is critical for the proper assembly of human immune responses. The clinical and immunological consequences of deficiencies in some of its components such as CARD9, CARD11, and MALT1 have been elucidated in detail. However, the scarcity of BCL10 deficient patients has prevented gaining detailed knowledge about this genetic disease. Only two patients with BCL10 deficiency have been reported to date. Here we provide an in-depth description of an additional patient with autosomal recessive complete BCL10 deficiency caused by a nonsense mutation that leads to a loss of expression (K63X). Using mass cytometry coupled with unsupervised clustering and machine learning computational methods, we obtained a thorough characterization of the consequences of BCL10 deficiency in different populations of leukocytes. We showed that in addition to the near absence of memory B and T cells previously reported, this patient displays a reduction in NK, γδT, Tregs, and TFH cells. The patient had recurrent respiratory infections since early childhood, and showed a family history of lethal severe infectious diseases. Fortunately, hematopoietic stem-cell transplantation (HSCT) cured her. Overall, this report highlights the importance of early genetic diagnosis for the management of BCL10 deficient patients and HSCT as the recommended treatment to cure this disease.Item Executive Summary of the Consensus Document on the Diagnosis and Management of Patients with Primary Immunodeficiencies(The Journal of Allergy and Clinical Immunology: In Practice, 2020) Cordero, Elisa; Goycochea Valdivia, Walter; Mendez Echevarría, Ana; M. Allende, Luis; Alsina, Laia; Bravo García Morato, María; Gil Herrera, Juana; Gudiol, Carlota; Len Abad, Óscar; López Medrano, Francisco; Moreno Pérez, David; Muñoz, Patricia; Olbrich, Peter; Sánchez Ramón, Silvia María; Soler Paracín, Pere; Aguilera Cros, Clara; Arostegui, Juan Ignacio; Badell Serra, Isabel; Carbone Campoverde, Javier Alberto; Fortún, Jesús; González Granado, Luis Ignacio; López Granados, Eduardo; Lucena, José Manuel; Parody, Rocío; Ramakers, Jan; Regueiro González-Barros, José Ramón; Rivière, Jacque G; Roca Oporto, Cristina; Rodríguez Pena, Rebeca; Santos Pérez, Juan Luis; Rodríguez Gallego, Carlos; Neth, OlafPrimary immunodeficiencies (PIDs) are rare, undiagnosed and potentially fatal diseases. Clinical manifestations of PID can be fatal or leave sequelae that worsen the quality of life of patients. Traditionally, the treatment of PIDs has been largely supportive, with the exception of bone marrow transplantation and, more recently, gene therapy. The discovering of new affected pathways, the development of new molecules and biologics, and the increasing understanding of the molecular basis of these disorders have created opportunities in PIDs therapy. This document aims to review current knowledge and to provide recommendations about the diagnosis and clinical management of adults and childre with PIDs based on the available scientific evidence taking in to account current practice and future challenges. A systematic review was conducted, and evidence levels based on the available literature are given for each recommendation where available. � 2020 American Academy of Allergy, Asthma & Immunology; Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica [Published by Elsevier Inc./Elsevier Espana]. All rights reserved.Item Human BCL10 Deficiency due to Homozygosity for a Rare Allele(Journal of Clinical Immunology, 2020) Van Den Rym, Ana; Perez de Diego, Rebeca; Sánchez Ramón, Silvia María; Amin SafaThe CARD-BCL10-MALT1 (CBM) complex is critical for the proper assembly of human immune responses. The clinical and immunological consequences of deficiencies in some of its components such as CARD9, CARD11, and MALT1 have been elucidated in detail. However, the scarcity of BCL10 deficient patients has prevented gaining detailed knowledge about this genetic disease. Only two patients with BCL10 deficiency have been reported to date. Here we provide an in-depth description of an additional patient with autosomal recessive complete BCL10 deficiency caused by a nonsense mutation that leads to a loss of expression (K63X). Using mass cytometry coupled with unsupervised clustering and machine learning computational methods, we obtained a thorough characterization of the consequences of BCL10 deficiency in different populations of leukocytes. We showed that in addition to the near absence of memory B and T cells previously reported, this patient displays a reduction in NK, γδT, Tregs, and TFH cells. The patient had recurrent respiratory infections since early childhood, and showed a family history of lethal severe infectious diseases. Fortunately, hematopoietic stem-cell transplantation (HSCT) cured her. Overall, this report highlights the importance of early genetic diagnosis for the management of BCL10 deficient patients and HSCT as the recommended treatment to cure this disease.