Juárez Martín-Delgado, Ignacio

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First Name
Last Name
Juárez Martín-Delgado
Universidad Complutense de Madrid
Faculty / Institute
Inmunología, Oftalmología y ORL
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Now showing 1 - 9 of 9
  • 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
    Major histocompatibility complex complement (MHC) Bf alleles show trans species evolution between man and chimpanzee
    (Nature, 2023-10-04) Arnaiz Villena, Antonio; Juárez Martín-Delgado, Ignacio; Martín Villa, José Manuel; Ignacio Juarez; Alejandro Sánchez-Orta; José Manuel Martín-Villa; Fabio Suarez-Trujillo
    AbstractHLA and disease studies by using single allele statistics have been fruitless during the last 40 years for explaining association pathogenesis of the associated diseases.Other approaches are necessary to untangle this puzzle. We aim to revisit complement alleleism in humans and primates for both studying MHC and disease association to complotypes and extended MHC haplotypes in order to also explain the positive directional selection of maintaining immune response genes (complement, MHC adaptive and MHC non-specific genes) that keeps these three type of genes together in a short chromosome stretch (MHC) for million years. These genes may be linked to conjointly avoid microbes attack and autoimmunity. In the present paper, it is obtained a new Bf chimpanzee allele, provisionaly named Patr-Bf*A:01,that differs from other Bf alleles by having CTG at eleventh codon of exon 2 in order to start the newly suggested methodology and explain functional and evolutionary MHC obscure aspects. Exons 1 to 6 of Ba fragment of Bf gene were obtained from chimpanzee. This new chimpanzee Factor B allele (Patr-Bf*A:01) is to be identical to a infrequent human Bf allele (SNP rs641153); it stresses the strong evolutive pressure upon certain alleles that are trans specific. It also may apply to MHC extended haplotipes which may conjointly act to start an adequate immune response. It is the first time that a complement MHC class III allele is described to undergo trans species evolution,in contrast to class I and class II alleles which had already been reported . Allelism of complement factors are again proposed for studying MHC complement genes, complotypes, and extended MHC haplotypes which may be more informative that single MHC marker studies.
  • Publication
    HLA study in Mexico Nahua/Aztec Amerindians: Close relatedness to the ancient Central America ethnic groups
    (Elsevier, 2023-05) Suarez Trujillo, Fabio; Vargas Alarcon, Gilberto; Juárez Martín-Delgado, Ignacio; Gil Martin, Roberto; Granados, Julio; Vaquero Yuste, Christian; Martín Villa, José Manuel; Arnaiz Villena, Antonio
    Nahua population (also named Aztec or Mexica) was studied for HLA class II genes in a Mexican rural city (Santo Domingo Ocotitlan, Morelos State) belonging to the nowadays Náhuatl speaking areas in Mexico. The most frequent HLA class II alleles were typical Amerindian (HLA-DRB1*04:07, DQB1*03:01 DRB1*04:03 or DRB1*04:04) and also were some calculated extended haplotypes (HLA-DRB1*04:07-DQB1*03:02,DRB1*08:02-DQB1*04:02, or DRB1*10:01-DQB1*05:01 among others). When using HLA-DRB1 Neís genetic distances, our isolated Nahua population was found to be close to other Central America Amerindians like the ancient-established Mayans or Mixe. This may suggest that Nahuas origin was also from Central America. It contrasts to legend that assumes they came from the North, and they built the Aztec Empire after submitting Central America neighbouring ethnic groups before 1519 CE when Spaniards led by Hernán Cortés arrived to Mexico
  • 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
    HLA in North Colombia Chimila Amerindians
    (Elsevier, 2018-04-13) Arnaiz Villena, Antonio; Palacio Grüber, Jose; Juárez Martín-Delgado, Ignacio; Hernández, Ennio; Muñiz, Ester; Bayona, Brayan; Campos, Cristina; Nieto, Jorge; Martín Villa, José Manuel; Silvera, Carlos
    HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.
  • 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
    HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients
    (Frontiers Media, 2021-09-07) Vaquero Yuste, Christian; Juárez Martín-Delgado, Ignacio; Molina Alejandre, Marta; Molanes López, Elisa María; López Nares, Adrián; Suárez Trujillo, Fabio; Gutiérrez Calvo, Alberto; Fernández-Cruz Pérez, Eduardo; Rodríguez Sainz, Carmen; Martín Villa, José Manuel; Arnaiz Villena, Antonio
    HLA-G is a non-classical class I HLA molecule that induces tolerance by acting on receptors of both innate and adaptive immune cells. When overexpressed in tumors, limits surveillance by the immune system. The HLA-G gene shows several polymorphisms involved in mRNA and protein levels. We decided to study the implication of two polymorphisms (rs371194629; 14bp INS/DEL and rs1063320; +3142 C/G) in paired tissue samples (tumoral and non-tumoral) from 107 Spanish patients with gastric adenocarcinoma and 58 healthy control individuals, to assess the possible association of the HLA-G gene with gastric adenocarcinoma susceptibility, disease progression and survival. The presence of somatic mutations involving these polymorphisms was also analyzed. The frequency of the 14bp DEL allele was increased in patients (70.0%) compared to controls (57.0%, p=0.025). In addition, the haplotype formed by the combination of the 14bp DEL/+3142 C variants is also increased in patients (54.1% vs 44.4%, p=0.034, OR=1.74 CI95% 1.05-2.89). Kaplan-Meier analysis revealed that 14bp DEL/DEL patients showed lower 5-year life-expectancy than INS/DEL or INS/INS (p=0.041). Adjusting for TNM staging (Cox regression analysis) disclosed a significant difference in death risk (p=0.03) with an expected hazard 2.6 times higher. Finally, no somatic mutations were found when comparing these polymorphisms in tumoral vs non-tumoral tissues, which indicates that this is a preexisting condition in patients and not a de novo, tumor-restricted, event. In conclusion, the variants predominant in patients were those increasing HLA-G mRNA stability and HLA-G expression, clearly involving this molecule in gastric adenocarcinoma susceptibility, disease progression and survival and making it a potential target for immunotherapeutic approaches.
  • Publication
    HLA‐G: Function, polymorphisms and pathology
    (Wiley, 2020-10) Suarez‐Trujillo, Fabio; López‐Nares, Adrián; Vaquero, Christian; Palacio‐Gruber, Jose; Arnaiz Villena, Antonio; Juárez Martín-Delgado, Ignacio; Martín Villa, José Manuel
    HLA-G immune modulatory genes and molecules are presently being studied by a widespread number of research groups. In the present study, we do not aim to be exhaustive since the number of manuscripts published every year is overwhelming. Instead, our aim is pointing out facts about HLA-G function, polymorphism and pathology that have been confirmed by several different researchers, together with exposing aspects that may have been overlooked or not sufficiently remarked in this productive field of study. On the other hand, we question whether performing mainly studies on HLA-G and disease associations is going to give a clear answer in the future, since 40 years of study of classical HLA molecules association with disease has still given no definite answer on this issue.
  • Publication
    HLA alleles and haplotypes in Sudanese population and their relationship with Mediterraneans
    (Nature, 2023-09-27) Juárez Martín-Delgado, Ignacio; Arnaiz Villena, Antonio; Martín Villa, José Manuel; Fabio Suarez-Trujillo; Sayda El-Safi; José Palacio-Gruber; Alejandro Sanchez-Orta; José Manuel Martin-Villa; Antonio Arnaiz-Villena
    AbstractThe contribution of migrated people from once green Sahara (about 10,000–6000 years bc) towards Mediterranean area had probably a double effect: both genetic and cultural connections have been described between Western Europe and North Africa. Sudanese populations from different ethnicities have been studied for HLA-A, -B, -DRB1 and -DQB1 antigens by a standard microlymphotoxicity method. Results found show that Nubians are genetically related with African Sub-Saharan populations and distant from other Sudanese tribes, who are closer to Mediterranean populations than to Sub-Saharan ones. This is concordant with other authors and meta-analysis data. Our present work is, to our knowledge, the first and only one HLA research that studies Sudanese people according to different Sudan ethnic groups: samples were collected before Sudan partition between North and South. A prehistoric genetic and peoples exchange between Africa and the Mediterranean basin may be observed and is supported with the results obtained in this Sudanese HLA study. However, demic diffusion model of agriculture and other anthropological traits from Middle East to West Europe/Maghreb do not exist: a more detailed Sahel and North African countries ancient and recent admixture studies are also being carried out which may clearer explain pastoralists/agriculture innovations origins in Eurafrican Mediterranean and Atlantic façade.