Person:
Juárez Martín-Delgado, Ignacio

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First Name
Ignacio
Last Name
Juárez Martín-Delgado
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Inmunología, Oftalmología y ORL
Area
Inmunología
Identifiers
UCM identifierORCIDScopus Author IDDialnet ID

Search Results

Now showing 1 - 10 of 14
  • Publication
    HLA genetic study in Iran Saqqez-Baneh Kurds: no genetic trace of Aryan invasions in Anatolian Turks and Kurds is found
    (Elsevier, 2022-08-03) Suarez Trujillo, Fabio; Juárez Martín-Delgado, Ignacio; Palacio Grüber, José Manuel de; Martin Villa, Jose Manuel; Amirzargar, Ali; Arnaiz Villena, Antonio
    Kurds are living at Middle East region comprising several countries (38 million people) and also have emigrated to Asia, Europe and America. Kurds from Iran have been HLA typed in the present work from Saqqez and Baneh towns, Kordestan province, Iran. Origin of Kurds is considered autochthonous from Anatolia and surrounding mountains :they have been referred as “the mountain people” by classic Persian, Greek and Roman authors. Present day Turks are also autochthonous from Anatolia, but they were not recognized by classical authors as living in the mountains and they speak a language of Asian origin that was imposed to Anatolia by a “elite” invasion without a noticeable high Asian gene input. Most frequent class I and class II HLA alleles found in Iranian Kurds population are: HLA‐A*24:02, A*02:01 and HLA‐B*35:01, and HLA‐DRB1*11:01, DRB1*03:02 and HLA‐DQB1*03:01; also, most frequent HLA extended haplotypes from this Iran Kurdish sample are not shared with Iranians but with Mediterranean, Turkish and Caucasus people. This is confirmed by Neighbour‐Joining and correspondence analysis studied together with the corresponding populations. Finally, our studies show that both Kurds and Turks are genetically original from Anatolian Peninsula and surrounding countries and that an apparent Asian genetic or Aryan invasion does not exist in the area.
  • Publication
    Higher prevalence of LAP+ (Latency TGFβ-Associated Peptide) T cells at the tissue level in patients with early gastric cancer
    (Elsevier, 2022-10-28) Aguinaga Barrilero, Ana; Juárez Martín-Delgado, Ignacio; Vaquero Yuste, Christian; Molina Alejandre, Marta; Gutiérrez Calvo, Alberto; Lasa, Inmaculada; López, Adela; Gómez, Remedios; Molanes López, Elisa M.; Martin Villa, Jose Manuel
    The presence of cells with regulatory functions in patients with cancer is one of the mechanisms whereby the immune system cannot confront tumor growth. We sought to determine the prevalence of immunoregulatory Tcell subpopulations, expressing the latency TGFβ-associated peptide (LAP), in patients with gastric adenocarcinoma. T cells were enriched from blood or gastric tissue (tumoral, TT or tumor-free, TF) samples from 22 patients, 6 with early (EGC) and 16 with advanced gastric cancer (AGC). CD4, CD8, LAP, FoxP3 and IFN-γ were measured by cytometry. CD8 + LAP + cells were increased at tumoral sites, especially in early stages of the disease, as compared to tumor-free explants (EGC 5.28 % [4.67–6.64]*; AGC 2.90 % [1.37–4.44]; TF 3.14 % [2.33–4.16]; *p < 0.05 vs TF). Likewise, the LAP+/CD8 + LAP- ratio is increased in gastric samples from patients with early disease (EGC 0.38 [0.30–0.45]*, AGC 0.12 [0.07–0.14]; TF 0.12 [0.09–0.31]; *p < 0.05 vs AGC). Disease progression is accompanied by decreased LAP membrane expression and, probably, increased LAP secretion, therefore limiting the response to the tumor.
  • Publication
    A Reliable and Standardizable Differential PCR and qPCR Methodology Assesses HER2 Gene Amplification in Gastric Cancer
    (MDPI, 2021-06-10) Juárez Martín-Delgado, Ignacio; Toro Fernandez, Juan Francisco; Vaquero Yuste, Christian; Molina Alejandre, Marta; Lasa, Inmaculada; Gomez, Remedios; Lopez, Adela; Martin Villa, Jose Manuel; Gutierrez, Alberto
    We have applied two PCR techniques, differential PCR (diffPCR) and qPCR for the identification of HER2 gene amplifications in genomic DNA of tumor and distal gastric samples from patients with gastric cancer. The diffPCR technique consists of the simultaneous amplification of the HER2 gene and a housekeeping gene by conventional PCR and the densitometric analysis of the bands obtained. We established a cut-off point based on the mean and standard deviation analyzing the DNA of 30 gastric tissues from patients undergoing non-cancer gastrectomy. diffPCR and qPCR yielded consistent results. HER2-overexpression was detected in 25% of patients and was further confirmed by immunohistochemistry and immunofluorescence. The approaches herein described may serve as complementary and reliable methods to assess HER2 amplification.
  • Publication
    Estudio de marcadores genéticos e inmunitarios relacionados con inmunoterapia en cáncer gástrico
    (Universidad Complutense de Madrid, 2021-07-12) Juárez Martín-Delgado, Ignacio; Martín Villa, José Manuel; Tsokos, George C.
    El cáncer es una enfermedad multifactorial con una serie de características definitorias: mantenimiento de las señales de proliferación, resistencia a la muerte celular, inmortalidad replicativa, inducción de angiogénesis, motilidad y metástasis, inestabilidad genómica y mutación, inflamación pro-tumoral, reprogramación del metabolismo energético y evasión de la respuesta inmunitaria antitumoral. Como parte de esta última característica, destaca la implicación del sistema inmunitario en la respuesta antitumoral, siguiendo un proceso denominado inmunoedición, que se compone de tres fases: eliminación del tumor por parte del sistema inmunitario, equilibrio entre la respuesta inmunitaria y los mecanismos supresores del tumor y, finalmente, escape del tumor e invasión de tejidos adyacentes y distales. El cáncer gástrico es el quinto tipo de tumor más frecuente en la población mundial, con más de un millón de muertes anuales en todo el mundo. Es uno de los tumores con mayor prevalencia de mutaciones somáticas, lo que facilita la formación de neo-antígenos tumorales y hace susceptible estos tumores para su tratamiento con diversos tipos de inmunoterapia. La inmunoterapia comprende una serie de tratamientos que promueven la estimulación del sistema inmunitario tendentes a la prevención o tratamiento de una enfermedad. La inmunoterapia contra el cáncer tiene como objetivo el bloqueo de vías de señalización protumorales, así como la estimulación (directa o indirecta) de la respuesta inmunitaria contra los tumores. En el caso concreto del cáncer gástrico, el tratamiento con anticuerpos bloqueantes de HER2 (trastuzumab) se emplea en emplea en pacientes HER+, mientras que los inhibidores de puntos del control del sistema inmunitaria únicamente están aprobados para el tratamiento de pacientes en estadios muy avanzados de la enfermedad, con enfermedad diseminada, y refractarios a quimio y radioterapia. La dificultad para el tratamiento de estos pacientes radica en la correcta determinación de biomarcadores que identifiquen a pacientes susceptibles de recibir inmunoterapia...
  • Publication
    Evolution and molecular interactions of major histocompatibility complex (MHC)-G, -E and -F genes
    (Springer Link, 2022-08) Suarez-Trujillo, Fabio; Juarez, Ignacio; Rodríguez-Sainz, Carmen; Palacio-Gruber, José; Vaquero-Yuste, Christian; Molina-Alejandre, Marta; Fernández-Cruz, Eduardo; Martin-Villa, José Manuel; Arnaiz Villena, Antonio; Juárez Martín-Delgado, Ignacio; Fernández-Cruz Pérez, Eduardo; Martín Villa, José Manuel
    AbstractClassicalHLA(Human Leukocyte Antigen) is the Major Histocompatibility Complex (MHC) in man. HLA genes and disease association has been studied at least since 1967 and no firm pathogenic mechanisms have been established yet.HLA-Gimmune modulation gene (and also-Eand-F) are starting the same arduous way: statistics and allele association are the trending subjects with the same few results obtained byHLAclassical genes, i.e., no pathogenesis may be discovered after many years of a great amount of researchers’ effort. Thus, we believe that it is necessary to follow different research methodologies: (1) to approach this problem, based on how evolution has worked maintaining together a cluster of immune-related genes (the MHC) in a relatively short chromosome area since amniotes to human at least, i.e., immune regulatory genes (MHC-G, -E and -F), adaptive immune classical class I and II genes, non-adaptive immune genes like (C2, C4 and Bf) (2); in addition to using new in vitro models which explain pathogenetics ofHLAand disease associations. In fact, this evolution may be quite reliably studied during about 40 million years by analyzing the evolution ofMHC-G, -E, -F, and their receptors (KIR—killer-cell immunoglobulin-like receptor, NKG2—natural killer group 2-, or TCR-T-cell receptor—among others) in the primate evolutionary lineage, where orthology of these molecules is apparently established, although cladistic studies show thatMHC-GandMHC-Bgenes are the ancestral class I genes, and that New World apesMHC-Gis paralogous and not orthologous to all other apes and manMHC-Ggenes. In the present review, we outline past and possible future research topics: co-evolution of adaptiveMHCclassical (class I and II), non-adaptive (i.e., complement) and modulation (i.e., non-classical class I) immune genes may imply that the study of full or part of MHC haplotypes involving several loci/alleles instead of single alleles is important for uncovering HLA and disease pathogenesis. It would mainly apply to starting research on HLA-G extended haplotypes and disease association and not only using single HLA-G genetic markers.
  • Publication
    A Reliable and Standardizable Differential PCR and qPCR Methodology Assesses HER2 Gene Amplification in Gastric Cancer
    (MDPI, 2021-06-10) Juárez Martín-Delgado, Ignacio; Toro Fernandez, Juan Francisco; Vaquero Yuste, Christian; Molina Alejandre, Marta; Lasa, Inmaculada; Gomez, Remedios; Lopez, Adela; Martín Villa, José Manuel; Gutierrez, Alberto
    We have applied two PCR techniques, differential PCR (diffPCR) and qPCR for the identification of HER2 gene amplifications in genomic DNA of tumor and distal gastric samples from patients with gastric cancer. The diffPCR technique consists of the simultaneous amplification of the HER2 gene and a housekeeping gene by conventional PCR and the densitometric analysis of the bands obtained. We established a cut-off point based on the mean and standard deviation analyzing the DNA of 30 gastric tissues from patients undergoing non-cancer gastrectomy. diffPCR and qPCR yielded consistent results. HER2-overexpression was detected in 25% of patients and was further confirmed by immunohistochemistry and immunofluorescence. The approaches herein described may serve as complementary and reliable methods to assess HER2 amplification.
  • Publication
    HLA-G: Too Much or Too Little? Role in Cancer and Autoimmune Disease
    (Frontiers, 2022-01-27) Martín Villa, José Manuel; Juárez Martín-Delgado, Ignacio; Fernández-Cruz Pérez, Eduardo; Arnaiz Villena, Antonio; Christian Vaquero-Yuste; Marta Molina-Alejandre; Fabio Suárez-Trujillo; Adrián López-Nares; José Palacio‐Gruber; Luis Barrera-Gutiérrez; Carmen Rodríguez-Sainz
    HLA-G is a non-classical HLA class I molecule with immunomodulatory properties. It was initially described at the maternal-fetal interface, and it was later found that this molecule was constitutively expressed on certain immuneprivileged tissues, such as cornea, endothelial and erythroid precursors, and thymus. The immunosuppressive effect of HLA-G is exerted through the interaction with its cognate receptors, expressed on immunocompetent cells, like ILT2, expressed on NK, B, T cells and APCs; ILT4, on APCs; KIR, found on the surface of NK cells; and finally, the co-receptor CD8. Because of these immunomodulatory functions, HLA-G has been involved in several processes, amongst which organ transplantation, viral infections, cancer progression, and autoimmunity. HLA-G neo-expression on tumors has been recently described in several types of malignancies. In fact, tumor progression is tightly linked to the presence of the molecule, as it exerts its tolerogenic function, inhibiting the cells of the immune system and favoring tumor escape. Several polymorphisms in the 3’UTR region condition changes in HLA-G expression (14bp and +3142C/G, among others), which have been associated with both the development and outcome of patients with different tumor types. Also, in recent years, several studies have shown that HLA-G plays an important role in the control of autoimmune diseases. The ability of HLA-G to limit the progression of these diseases has been confirmed and, in fact, levels of the molecule and several of its polymorphisms have been associated with increased susceptibility to the development of autoimmune diseases, as well as increased disease severity. Thus, modulating HLA-G expression in target tissues of oncology patients or patients with autoimmune diseases may be potential therapeutic approaches to treat these pathological conditions.
  • Publication
    Higher prevalence of LAP+ (Latency TGFβ-Associated Peptide) T cells at the tissue level in patients with early gastric cancer
    (Elsevier, 2022-12) Aguinaga Barrilero, Ana; Juárez Martín-Delgado, Ignacio; Vaquero Yuste, Christian; Molina Alejandre, Marta; Gutiérrez Calvo, Alberto; Lasa, Inmaculada; López, Adela; Gómez, Remedios; Molanes López, Elisa María; Martín Villa, José Manuel
    The presence of cells with regulatory functions in patients with cancer is one of the mechanisms whereby the immune system cannot confront tumor growth. We sought to determine the prevalence of immunoregulatory T-cell subpopulations, expressing the latency TGFβ-associated peptide (LAP), in patients with gastric adenocarcinoma. T cells were enriched from blood or gastric tissue (tumoral, TT or tumor-free, TF) samples from 22 patients, 6 with early (EGC) and 16 with advanced gastric cancer (AGC). CD4, CD8, LAP, FoxP3 and IFN-γ were measured by cytometry. CD8 + LAP + cells were increased at tumoral sites, especially in early stages of the disease, as compared to tumor-free explants (EGC 5.28 % [4.67-6.64]*; AGC 2.90 % [1.37-4.44]; TF 3.14 % [2.33-4.16]; *p < 0.05 vs TF). Likewise, the LAP+/CD8 + LAP- ratio is increased in gastric samples from patients with early disease (EGC 0.38 [0.30-0.45]*, AGC 0.12 [0.07-0.14]; TF 0.12 [0.09-0.31]; *p < 0.05 vs AGC).Disease progression is accompanied by decreased LAP membrane expression and, probably, increased LAP secretion, therefore limiting the response to the tumor.
  • Publication
    Splicing factor SRSF1 controls T cell homeostasis and its decreased levels are linked to lymphopenia in systemic lupus erythematosus
    (Oxford University Press, 2020-03-24) Katsuyama, Takayuki; Juárez Martín-Delgado, Ignacio; Krishfield, Suzanne M; Kyttaris, Vasileios C; Moulton, Vaishali R
    Objective: Lymphopenia is a frequent clinical manifestation and risk factor for infections in SLE, but the underlying mechanisms are not fully understood. We previously identified novel roles for the RNA-binding protein serine arginine-rich splicing factor 1 (SRSF1) in the control of genes involved in signalling and cytokine production in human T cells. SRSF1 is decreased in T cells from patients with SLE and associates with severe disease. Because SRSF1 controls the expression of apoptosis-related genes, we hypothesized that SRSF1 controls T cell homeostasis and, when reduced, leads to lymphopenia. Methods: We evaluated SRSF1 expression in T cells from SLE patients by immunoblots and analysed its correlation with clinical parameters. T cell conditional Srsf1 knockout mice were used to evaluate lymphoid cells and apoptosis by flow cytometry. Quantitative PCR and immunoblots were used to assess Bcl-xL mRNA and protein expression. SRSF1 overexpression was performed by transient transfections by electroporation. Results: We found that low SRSF1 levels correlated with lymphopenia in SLE patients. Selective deletion of Srsf1 in T cells in mice led to T cell lymphopenia, with increased apoptosis and decreased expression of the anti-apoptotic Bcl-xL. Lower SRSF1 expression correlated with low Bcl-xL levels in T cells and lower Bcl-xL levels associated with lymphopenia in SLE patients. Importantly, overexpression of SRSF1 rescued survival of T cells from patients with SLE. Conclusion: Our studies uncovered a previously unrecognized role for SRSF1 in the control of T cell homeostasis and its reduced expression as a molecular defect that contributes to lymphopenia in systemic autoimmunity.
  • Publication
    An Experimental DUAL Model of Advanced Liver Damage
    (Lippincott, Williams & Wilkins, 2021-06) Benede Ubieto, Raquel; Estévez Vázquez, Olga; Guo, Feifei; Chen, Chaobo; Gómez Del Moral Martín-Consuegra, Manuel María; Lamas Paz, Aranzazu; Morán, Laura; López Alcántara, Nuria; S. Mazariegos, Marina; Zheng, Kang; Juárez Martín-Delgado, Ignacio; Martín Villa, José Manuel; Asensio, Iris; Vaquero Martín, Francisco Javier; Peligros Gómez, María Isabel; Romero Gómez, Manuel; Bañares Cañizares, Rafael; Cubero Palero, Francisco Javier; Nevzorova, Yulia
    Individuals exhibiting an intermediate alcohol drinking pattern in conjunction with signs of metabolic risk present clinical features of both alcohol-associated and metabolic-associated fatty liver diseases. However, such combination remains an unexplored area of great interest, given the increasing number of patients affected. In the present study, we aimed to develop a preclinical DUAL (alcohol-associated liver disease plus metabolic-associated fatty liver disease) model in mice. C57BL/6 mice received 10% vol/vol alcohol in sweetened drinking water in combination with a Western diet for 10, 23, and 52 weeks (DUAL model). Animals fed with DUAL diet elicited a significant increase in body mass index accompanied by a pronounced hypertrophy of adipocytes, hypercholesterolemia, and hyperglycemia. Significant liver damage was characterized by elevated plasma alanine aminotransferase and lactate dehydrogenase levels, extensive hepatomegaly, hepatocyte enlargement, ballooning, steatosis, hepatic cell death, and compensatory proliferation. Notably, DUAL animals developed lobular inflammation and advanced hepatic fibrosis. Sequentially, bridging cirrhotic changes were frequently observed after 12 months. Bulk RNA-sequencing analysis indicated that dysregulated molecular pathways in DUAL mice were similar to those of patients with steatohepatitis. Conclusion: Our DUAL model is characterized by obesity, glucose intolerance, liver damage, prominent steatohepatitis and fibrosis, as well as inflammation and fibrosis in white adipose tissue. Altogether, the DUAL model mimics all histological, metabolic, and transcriptomic gene signatures of human advanced steatohepatitis, and therefore serves as a preclinical tool for the development of therapeutic targets.