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[Abstract] Creating project-based learning experiences in the classroom where students learn in a team to solve complex problems and to develop creative and critical thinking is a challenge. Design Sprint (DS) is an agile methodology (implemented in 5 days) with the goal of creating innovative design based on user needs (User Experience). The objective of this work was to develop an Engineering Drawing classroom experience linked to the context of the current COVID-19 pandemic with the Design Sprint methodology. The experience had to involve the integration of theory and practice, the application of knowledge, the development of both hard and soft skills, and the empowerment of students to conduct research. 56 first-year students following three STEAM degrees at the University of A Coruña participated in this experience. The activities were designed for both face-to-face and remote learning. Microsoft Teams and Moodle were used for tutoring and for monitoring student progress. The Moodle Workshop tool was used for the evaluation of the prototypes that were developed and the projects were evaluated by video. The students defended their projects through a presentation in lightning talk format (Ignite). Evaluation rubrics were used following a triple approach: co-evaluation, hetero-evaluation and self-evaluation. The 3D design of the projects was developed with Autodesk software. A total of 18 projects were developed. Once the projects were completed, a survey was administered to evaluate the levels of student satisfaction. The survey results were very positive. The Design Sprint projects also showed positive effects on grades. The Design Sprint method has promoted an interactive learning environment. In addition to its simplicity, a further advantage of DS method is that all student dedication is planned. Students were therefore less likely to feel overloaded, all of which helps with better time management. The DS methodology is multipurpose, so it can be applied to various fields and subjects.

[Resumo] A metodoloxía de Deseño Centrado en Humanos (DCH) busca analizar un problema desde un punto de vista máis aberto, dinámico e creativo. No contexto educativo, o DCH permite a creación de experiencias que integran teoría e práctica. Ademais, o método de DCH fomenta a participación activa do alumnado. Neste traballo, recóllese unha experiencia dun traballo desenvolvido empregando a metodoloxía DCH cun enfoque de Aprendizaxe-Servizo (ApS) no contexto dos proxectos STEMbach ofertados pola Escola Politécnica de Enxeñaría de Ferrol (EPEF) da Universidade da Coruña. En concreto, tratouse dun proxecto de Deseño, Modelado e Impresión 3D pertencente ao bienio 2020-2022 con alumnado do Colexio Tirso de Molina de Ferrol. O obxectivo do proxecto foi a creación de recursos didácticos para axudar a nenos e nenas do primeiro ciclo de educación primaria con dificultades no proceso de lectoescritura. Neste proxecto traballaron en equipo un total de 4 alumnas titorizadas por dous docentes do centro. O proxecto foi dirixido por cinco docentes universitarios. [Abstract] The Human-Centered Design (HCD) methodology seeks to analyze a problem from a more open, dynamic, and creative point of view. In the educational context, the HCD allows the creation of experiences that integrate theory and practice. In addition, the HCD method encourages the active participation of students. This work describes, an experience of a work developed using the HCD methodology with a Service-Learning approach in the context of the STEMbach projects offered by the Polytechnic School of Engineering of Ferrol (EPEF) of the University of A Coruña. Specifically, it describes the development of a project of Design, Modeling and 3D Printing with students from the Tirso de Molina School of Ferrol. The objective of the project was the creation of didactic resources to help children of the first cycle of primary education (6-8 years old) with difficulties in the process of reading and writing. A total of 4 students worked as a team, supervised by two teachers of the school. The project was directed by five university teachers. http://hdl.handle.net/2183/32493

13 pages, 5 tables, 7 figures.-- This is an open access article distributed under the Creative Commons Attribution License, Every year, millions of tons of fish waste are generated from fishing activities, and a similar amount is discarded and returned to the sea as unwanted catches. This material can be used as a biological source for many potential new added-value products, such asobtaining hyaluronic acid from fish eyeballs or extracting collagen from fish skin, but there are not many utilities for fish bones yet. This work tackles the transformation of fish discards into calcium phosphates. Discards from scorpionfish (Scorpaena scrofa) and Atlantic horse mackerel (Trachurus trachurus), as well as by-products generated from aquaculture activities (heads and trimmings frames) of salmon (Salmon salar), were used to obtain calcium phosphate. Biphasic carbonated hydroxyapatite (HA) /beta-tricalcium phosphate (TCP) material was obtained. The biphasic HA-TCP material has a promising range of applications in the biomedical field based on its similarity to calcium phosphates found in human bones in terms of crystallite size and carbonate content. The presence of Na, Mg, Sr, and K ions in the HA-TCP material is very beneficial, since they contribute to bone metabolism and cell adhesion, This work was partially supported by the EU research project Bluehuman (EAPA_151/2016 Interreg Atlantic Area), and by Xunta de Galicia (ED431C 2019/23, ED481D 2017/010, ED481B 2016/047-0). REVAL-Lab also wants to thank to GAIN (EU, Horizon 2020 Framework Research and Innovation Programme under GA n. 773330) and Xunta de Galicia (Grupos de Potencial Crecimiento, IN607B 2018/19) for the financial support of this investigation

[Resumo] Crear experiencias de aprendizaxe a través de proxectos na aula nas que os alumnos aprendan en equipo a resolver problemas complexos e desenvolvan o pensamento creativo e crítico, resulta un desafío. Design Thinking é unha metodoloxía cuxa meta é crear un deseño innovador baseado nas necesidades do usuario (User Experience). Empregando esta ferramenta, desenvolveuse na materia de Expresión Gráfica unha experiencia de deseño, modelado e impresión 3D ligada ao contexto actual de pandemia producida polo COVID-19. Nesta experiencia participaron estudantes de primeiro curso de tres graos do ámbito STEAM da Universidade de A Coruña. As actividades expuxéronse de tal maneira que se puidesen facer de forma presencial ou a distancia. A titorización e seguimento do progreso dos alumnos fíxose a través de Microsoft Teams e Moodle. Empregouse a ferramenta Taller de Moodle para a avaliación dos prototipos desenvolvidos. Os resultados da enquisa foron moi positivos. Os proxectos Design Thinking tamén tiveron un efecto positivo nas cualificacións. [Abstract] Creating learning experiences through classroom projects in which students learn as a team to solve complex problems and develop creative and critical thinking is a challenge. Design Thinking is a methodology whose goal is to create an innovative design based on the user's needs (User Experience). Using this tool, an experience of design, modeling and 3D printing linked to the current context of the pandemic produced by COVID-19 was developed in the subject of Graphic Expression. This experience involved first year students of three STEAM degrees of the University of A Coruña. The activities were planned in such a way that they could be done in person or remotely. Tutoring and monitoring of student progress was done through Microsoft Teams and Moodle. The Moodle Workshop tool was used for the evaluation of the developed prototypes. The survey results were very positive. Design Thinking projects also had a positive effect on the grades. http://hdl.handle.net/2183/28796

The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses, trimming peptides and loading onto HLA class I molecules. Coding single nucleotide polymorphisms within ERAP1 are associated with autoimmune diseases, viral infections, and cancer development. Our purpose was to analyze the influence of ERAP1 variants on fibrogenesis in hepatitis C virus (HCV)–infected patients. A range of ERAP1 polymorphisms were genotyped in 722 unrelated Caucasian patients diagnosed with chronic HCV from two Spanish cohorts. Patients were classified according to their fibrosis stage. Paraffin-embedded tissue microarrays were constructed to assess ERAP1 expression (HCV = 38; alcoholic = 20) by immunohistochemistry. A statistical algorithm was applied to derive a fibrogenesis prediction model. The ERAP1 variants rs30187/T (K528, pc

Currently, there is great interest in reducing the consumption of fossil fuels (and other non-renewable energy sources) in order to preserve the environment, smart buildings are commonly proposed for this purpose as they are capable of producing their own energy and using it optimally. However, at times, solar energy is not able to supply the energy demand fully, it is mandatory to know the quantity of energy needed to optimize the system. This research focuses on the prediction of output temperature from a solar thermal collector. The aim is to measure solar thermal energy and optimize the energy system of a house (or building). The dataset used in this research has been taken from a real installation in a bio-climate house located on the Sotavento Experimental Wind Farm, in north-west Spain. A hybrid intelligent model has been developed by combining clustering and regression methods such as neural networks, polynomial regression, and support vector machines. The main findings show that, by dividing the dataset into small clusters on the basis of similarity in behavior, it is possible to create more accurate models. Moreover, combining different regression methods for each cluster provides better results than when a global model of the whole dataset is used. In temperature prediction, mean absolute error was lower than 4 ∘ C.

An important factor affecting the success in the setting of related haploidentical hematopoietic stem cell transplantation (HSCT) is the graft-versus-leukemia effect mediated by natural killer (NK) cells when the donor displays NK alloreactivity versus the recipient. NK cell function is regulated by killer immunoglobulin-like receptors (KIR) and it has been described that donor KIR genotype influences transplantation outcome. This has led to a requirement of laboratories to have a quality assurance program for validation and control of their KIR genotyping methods. The goal of the 1st and 2nd Spanish KIR Genotyping Workshops was to provide an external proficiency testing program in KIR genotyping for Spanish immunology and transplant laboratories. These workshops were conducted during the years 2014-2016 and consisted of 17 participating laboratories typing a set of 20 samples. The presence/absence of 16 mandatory KIR loci (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DP1, 3DL1, 3DL2, 3DL3, 3DS1, and 3DP1) was evaluated per sample. Methods for KIR genotyping included polymerase chain reaction with the use of sequence-specific primers and sequence-specific oligoprobes. Consensus typing was reached in all samples, and the performance of laboratories in external proficiency testing was satisfactory in all cases. The polymorphism detected in the small sample studied in both workshops is indicative of an ample variety of KIR gene profiles in the Spanish population.

Superparamagnetic nanoparticles (MNP) have attracted much interest for medical applications, like magnetic cell separation, magnetic resonance imaging, drug delivery and hyperthermia In this work, 10 nm MNP were functionalized with human α-MICA antibody, via biotin-streptavidin conjugation, due to the importance of MICA receptor in antitumor immunity. The potentiality of the nanoparticles has been tested in vitro with two different cell lines: HeLa (with MICA ligands on surface) and HL-60 (without MICA ligands). MNP tagged HeLa cells were effectively separated by application of a magnetic field gradient. TEM micrographs were performed after magnetic separation, proving intracellular presence of the functionalized MNP. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Servicio de Inmunologia, Hospital Universitario Virgen de la Arrixaca, Murcia, Espana Servicio de Inmunologia, Hospital Marques de Valdecilla, Santander, Espana Histocompatibilidad, Centro de Transfusion de la Comunidad de Madrid, Madrid, Espana Unidad de Inmunologia, Hospital Insular de Gran Canaria, Las Palmas de Gran Canaria, Espana Unidad de Inmunologia, Hospital Clinico, Salamanca, Espana Servicio de Inmunologia, Hospital Infanta Cristina, Badajoz, Espana Servicio de Inmunologia, Hospital Virgen del Rocio, Sevilla, Espana Servicio de Inmunologia, Hospital 12 de Octubre, Madrid, Espana Unidad de Inmunologia, Hospital San Pedro, Logrono, Espana Servicio de Inmunologia, Complejo Hospitalario Universitario, A Coruna, Espana Servicio de Inmunologia, Hospital Carlos Haya, Malaga, Espana Servicio de Inmunologia, Clinica Universitaria de Navarra, Pamplona, Espana Unidad de Inmunologia, Hospital General, Albacete, Espana ana

Introduction The activating MICA/NKG2D interaction is involved in the response of intraepithelial lymphocytes (IELs) in coeliac disease (CD). The aim of this study was to investigate the expression of NKG2D ligands (MICA, MICB), IL-15 and NKG2D receptor in gut mucosa of CD patients, and the correlation with the severity of histological damage. Patients and methods Intestinal biopsies from 20 CD patients and five healthy controls were selected. All patients were positive for anti-transglutaminase 2 antibodies and for DQ2 or DQ8. Patients were divided into two groups according to their grade of mucosal impairment: ten each with mild and severe mucosal damage (MMD and SMD, respectively). The expression of proposed genes was determined at mRNA level. MICA expression was also determined by immunohistochemistry. Results Overexpression of MICA and MICB was observed in biopsies from coeliac patients compared to healthy controls ( P P Conclusions Our results suggest that NKG2D ligands may play an important role during the onset of the inflammatory process in the early stages of the development of coeliac disease.

[Resumen]El presente trabajo de investigación aborda el problema del bajo rendimiento académico alcanzado en los estudios de Ingeniería. Se realiza el análisis estadístico descriptivo y de correlación de los resultados académicos del alumnado que ha cursado las titulaciones de Ingeniería Técnica Industrial, especialidades Electricidad y Electrónica Industrial, pertenecientes a la Universidad de A Coruña, tal como figuran en su expediente académico. Mediante la aplicación de técnicas avanzadas de regresión, se desarrollan modelos de predicción del itinerario académico del estudiantado a lo largo de toda su carrera universitaria, de tal forma que, se logra predecir las calificaciones obtenidas y las convocatorias agotadas en las materias que cada alumno curse durante el primer año académico, a partir de la nota de acceso a la universidad. El resto de calificaciones y convocatorias de las materias que componen la titulación se pueden predecir en cualquier momento de la trayectoria académica del estudiante, incorporando al modelo las notas de las materias según se vayan superando. Los modelos desarrollados permiten conseguir el principal objetivo propuesto de conocer por adelantado el rendimiento académico de cada estudiante, y se pueden aplicar para la predicción del rendimiento individual del alumnado, [Resumo]O presente traballo de investigación aborda o problema do baixo rendemento académico alcanzado nos estudos de Enxeñaría. Realízase a análise estatístico descritivo e de correlación dos resultados académicos do alumnado que cursou as titulacións de Enxeñaría Técnica Industrial, especialidades Electricidade e Electrónica Industrial, pertencentes á Universidade da Coruña, tal como figuran no seu expediente académico. Mediante a aplicación de técnicas avanzadas de regresión, desenvólvense modelos de predición do itinerario académico do alumnado ao longo de toda a súa carreira universitaria, de tal forma que, se logra predicir as cualificacións obtidas e as convocatorias esgotadas nas materias que cada alumno curse durante o primeiro ano académico, a partir da nota de acceso á universidade. O resto de cualificacións e convocatorias das materias que compoñen a titulación pódense predicir en calquera momento da traxectoria académica do estudante, incorporando ao modelo as notas das materias segundo se vaian superando. Os modelos desenvolvidos permiten conseguir o principal obxectivo proposto de coñecer por adiantado o rendemento académico de cada estudante, e pódense aplicar para a predición do rendemento individual do alumnado., [Abstract]In this work, we deal with the problem of poor academic performance among students of Engineering Degrees. We carry out the statistical descriptive and correlation analysis of the academic achievements of the undergraduates of the Electrical and Industrial Electronics specialities in the Technical Industrial Engineering from the University of A Coruña. Applying advanced regression techniques, prediction models for the academic performance of the students are developed. Therefore, the marks and the number of failed exams throughout the first year of the degree are obtained from the corresponding of secondary education. The marks and the number of left exams needed in order to pass the remaining courses can be predicted at any time during the degree. In order to do that, the marks already achieved are included into the model. Eventually, the main goal of this work is accomplished; the performance of each student can be anticipated. Moreover, the developed models can be applied for the prediction of the individual academic achievements of each student.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that primarily involves the axial skeleton and the sacroiliac joint, but may also affect peripheral joints and entheses. AS susceptibility is clearly attributable to genetic factors and the link between human leukocyte antigen (HLA)-B27 and AS is the strongest association between an HLA class I molecule and a disease. However, there is evidence for the involvement of other, non-B27 factors within the major histocompatibility complex (MHC) in AS susceptibility. MHC class I is clearly the most significant genetic region for the disease, although most of the genetic association of this region is driven by HLA-B27. Moreover, several studies have investigated the MHC class II region and its association with AS. This review summarizes the current findings concerning the MHC genetics of the disease, focusing in particular on the associations of HLA with AS found in different ethnic populations throughout the world, and the possible mechanisms underlying them.

High-pressure ventilation triggers different inflammatory and matrix remodeling responses within the lung. Although some of them may cause injury, the involvement of these mediators in repair is largely unknown. To identify mechanisms of repair after ventilator-induced lung injury (VILI), mice were randomly assigned to baseline conditions (no ventilation), injury [90 min of high-pressure ventilation without positive end-expiratory pressure (PEEP)], repair (injury followed by 4 h of low-pressure ventilation with PEEP), and ventilated controls (low-pressure ventilation with PEEP for 90 and 330 min). Histological injury and lung permeability increased during injury, but were partially reverted in the repair group. This was accompanied by a proinflammatory response, together with increases in TNF-α and IFN-γ, which returned to baseline during repair, and a decrease in IL-10. However, macrophage inflammatory protein-2 (MIP-2) and matrix metalloproteinases (MMP)-2 and -9 increased after injury and persisted in being elevated during repair. Mortality in the repair phase was 50%. Survivors showed increased cell proliferation, lower levels of collagen, and higher levels of MIP-2 and MMP-2. Pan-MMP or specific MMP-2 inhibition (but not MIP-2, TNF-α, or IL-4 inhibition) delayed epithelial repair in an in vitro wound model using murine or human alveolar cells cultured in the presence of bronchoalveolar lavage fluid from mice during the repair phase or from patients with acute respiratory distress syndrome, respectively. Similarly, MMP inhibition with doxycycline impaired lung repair after VILI in vivo. In conclusion, VILI can be reverted by normalizing ventilation pressures. An adequate inflammatory response and extracellular matrix remodeling are essential for recovery. MMP-2 could play a key role in epithelial repair after VILI and acute respiratory distress syndrome.

The role of natural killer (NK) cells in solid organ transplantation is not well established, although several recent reports highlight the importance of the activating receptor NKG2D and its ligands in the development of rejection during transplantation. The human NKG2D ligands (MICA and MICB) are induced in allografts during acute and chronic rejection, and the presence of anti-MICA antibodies is correlated with a higher incidence of rejection. The binding of these ligands to its receptor NKG2D activates NK cells, enhances the functions of effectors, and allows NK cells to function as a bridge between innate and adaptive immunity associated with the transplantation. In fact, blockage of NKG2D with the anti-NKG2D monoclonal antibodies prolongs graft survival and prevents CD28-independent rejection in heart and skin allograft mouse models. Furthermore, the current immunosuppressive therapies can modulate the expression of NK cell receptors and consequently the effector functions of NK cells. That is particularly important during the first few months after transplantation, when the susceptibility to opportunistic viral infections is higher and NKG2D has an essential role. In this review, we analyze in detail the potential role of the NKG2D-activating receptor and its ligands in the immune responses during the outcome of solid organ transplantation. These findings open a new pathway for therapeutic intervention that can contribute to tolerance in solid organ transplantation.

Objective The killer cell immunoglobulin-like receptors (KIRs) form a group of regulatory molecules that specifically recognize HLA class I molecules. The aim of this study was to analyze the possible contribution of the KIR3DL1 and KIR3DS1 alleles, in addition to HLA–B27, in the susceptibility to ankylosing spondylitis (AS) in a population of individuals from Spain. Methods We genotyped the KIR3DS1 and KIR3DL1 alleles in 2 cohorts of patients with AS and healthy control subjects. In total, 270 patients with AS and 435 healthy, HLA–B27–positive matched control subjects from Spain were enrolled. The KIR3DS1 and KIR3DL1 alleles were genotyped by sequence-specific oligonucleotide probe–polymerase chain reaction, and their association with AS was analyzed. All individuals were typed for HLA–B. Results The KIR3DS1*013 allele was solely responsible for the increased frequency of the activator receptor KIR3DS1 in patients with AS compared with healthy HLA–B27–positive control subjects (35.7% versus 22.6% [P = 10−6], odds ratio 1.90, 95% confidence interval 1.50–2.40). The increased frequency of the KIR3DS1*013 allele in patients with AS was independent of the presence or absence of the HLA–Bw4I80 epitope. Moreover, the null allele KIR3DL1*004 was a unique inhibitory KIR3DL1 allele that showed a negative association with AS in the presence of HLA–Bw4I80. Conclusion The increased frequency of the KIR3DS1*013 allele in patients with AS is clearly independent of the presence of the HLA–Bw4I80 epitope, whereas the presence of inhibitory allotypes such as KIR3DL1*004 demonstrated a negative association in patients with AS in the presence of HLA–Bw4I80. As a consequence, the influence of KIR genotypes on AS susceptibility would be mediated by a general imbalance between protective/inhibitory and risk/activating allotypes.

Background. Noninvasive tests measuring cellular immunity could help predict immunologic risk and subsequent allograft dysfunction in transplant patients. CD25 is a promising marker of activation. Recent descriptions of CD127 expression as a discriminating factor between regulatory and activated T cells suggest its potential utility. Methods. Expression of CD 127 in CD4+CD25 high T cells was analyzed by flow cytometry in peripheral blood from 62 renal transplanted patients and 30 healthy controls. Forty patients presented stable graft function and 22 suffered renal failure. Results. Renal transplant patients showed higher levels of CD127 high and a lower frequency of CD 127 low than healthy controls (0.63% vs. 0.29% [P

Background. Several reports showed a contribution of anti-MICA (major histocompatibility complex class I chain-related molecule A) antibodies (Abs) to the development of acute and chronic rejection. Identification of the epitopes to which the Abs bind may help to determine immunoreactive regions essential for the major histocompatibility complex compatibility between donor and recipients, leading to the best outcome of the transplant. Methods. Sera from 284 kidney transplant patients were screened for anti-MICA Abs by Luminex assay. MICA allele typing of the recipients was determined. The epitopes of MICA were mapped by screening a synthesized library of overlapping peptides from the extracellular domains of the protein against the sera from kidney transplant patients with anti-MICA Abs. Results. Antibodies against MICA were detected in 50 of 284 patients (17.6%) and correlated with the development of acute rejection. Nine antigenic regions were immunoreactive with anti-MICA Abs in the sera samples. Four of these continuous epitopes mapped to polymorphic amino acids (aa). Five antigenic regions were shared epitopes found in all the MICA alleles. The polymorphic residues, 173 (E/K), 175 (S/G), and 181 (R/T), had determined allele-specific epitopes (reactivity patterns 1 and 2). In contrast, the aa 208Y and 213T were implicated in the cross-reactivity among alleles. Conclusions. The presence of anti-MICA Abs could be an important marker for diagnosis because of their contribution to the outcome of the graft, regardless of presence of anti-HLA Abs. Additionally, the identification of epitopes revealed the in vivo antigens of the transplant and is spurring the development of new matching strategies to reduce the incidence of acute and chronic rejection.

NKG2D is one of the best characterized activating receptors on Natural Killer (NK) and CD8+ T cells. This receptor recognizes several different ligands (MICA/MICB and ULBPs) induced by cellular stress and infection. In addition to the role described in cancer surveillance, recent data highlight the importance of NKG2D and its ligands in organ transplantation. Allografts show evidence of MICA and MICB expression in both acute and chronic rejection. The presence of anti-MICA antibodies has been correlated with incidence of graft rejection. Furthermore, NKG2D-ligand engagement activates NK cells, which provides T-cell costimulation, and enhances antigen specific CTL-mediated cytotoxicity. Activated NK cells may function as a bridge between innate and adaptive immunity associated with transplantation. Activated NK cells in response to IL-15 can also trigger organ rejection through NKG2D and affect the maturation of both donor and recipient antigen presenting cells (APCs) and ultimately the T-cell allogeneic response. Regulatory T cells, which modulate T-cell responses in organ transplantation and infections, were reduced in numbers by NK cells exposed to intracellular pathogens, possibly via interaction with one NK2GD receptor. Blockage of NKG2D-NKG2D-L interactions provides a novel pathway for development of inhibitors. These studies have important clinical and therapeutic implications in solid organ transplantation.

NKG2D is an activating receptor expressed by NK and T cells. NKG2D ligands show a restricted expression in normal tissues, but they are frequently overexpressed in cancer and infected cells. The binding of NKG2D to its ligands activates NK and T cells and promotes cytotoxic lysis of the cells expressing these molecules. The mechanisms involved in the expression of the ligands of NKG2D play a key role in the recognition of stressed cells by the immune system and represent a promising therapeutic target for improving the immune response against cancer or autoimmune disease. In this review, we analyse the recent advances in understanding the regulation of NKG2D ligand expression and their therapeutic implications.

The role of MICA antibodies in acute heart allograft rejection was examined utilizing 190 pre- and post-transplant serum samples from 44 patients collected during the first year after transplantation. MICA antibodies were detected by CDC test on recombinant cell lines and by the newly developed Luminex MICA antibody detection assay. Additionally, MICA expression was analyzed by 'real time' RT-PCR and by immunohistochemistry in 10 endomyocardial biopsies. Only two subjects had HLA antibodies post-transplant. Nevertheless, MICA antibodies were found in a significant number of subjects. The prevalence of MICA antibodies was significantly higher among those with severe acute rejection (AR) than in those without rejection (60.7% vs. 14.3%, p = 0.0038 by CDC; 55.5% vs. 5.7%, p = 0.0020 by Luminex). In most cases, the appearance of MICA antibodies post-transplant precedes AR. Following transplantation, MICA up-regulation correlated with histological evidence of severe rejection. Monitoring for MICA antibodies post-transplant may be useful to establish new risk factors for acute rejection.

The objective of this retrospective study was to evaluate the role of MICA in heart graft acceptance. Pre- and post-transplant sera from 31 patients were evaluated for MICA antibodies by cytotoxicity on recombinant cell lines and soluble MICA (sMICA) concentrations by ELISA. The results demonstrated that the patients with post-transplant anti-MICA antibodies were at a high risk for the development of severe acute rejection (AR) (p

It is well known that certain HLA class II alleles confer an increased risk for developing multiple sclerosis (MS). Recent studies have suggested HLA class I as a region that may also contribute to the development of MS. In this study, we investigated the association between HLA-DR, HLA-B alleles, and major histocompatibility complex (MHC) class I-chain-related gene A (MICA) transmembrane (MICA-TM) polymorphisms and disease progression in 104 MS patients and 116 healthy controls. DR1 was found to be decreased in patients when compared with controls (p(c) = 0.012). Neither HLA-B nor HLA-DR alleles were found to be associated with MS susceptibility. Furthermore, the prevalence of MICA-A5 in patients with relapsing MS was 9% while the prevalence in progressive forms was 42% (p(c) = 0.0015). The extended haplotypes related to MICA-TM5 that were found in our population were DR7-MICA5-B64 (EH 64.1, delta(s) = 0.38), DR4-MICA5-B62 (EH 62.1, delta(s) = 0.28), and DR11-MICA5-B35 (EH35.1, delta(s) = 0.10), but none of them were found to be associated to MS susceptibility or disease progression. Our data could indicate a possible role of MICA-TM in MS prognosis.

The HLA-Cw*0602 has been associated with psoriasis in different ethnic groups. But, it remains unclear whether HLA-C is the PSORS1 gene (the psoriasis gene in the MHC). Thus, several case-control studies have been performed in order to investigate whether HLA-C itself determines the susceptibility to the disease. We studied 59 Jewish patients with type I psoriasis and 79 matched controls. Polymorphic genes and markers from HLA-B (centromeric to HLA-C) to the corneodesmosin (CDSN) gene (telomeric to HLA-C) were genotyped in order to determine their contribution to the susceptibility to psoriasis. Neither HLA-Cw*0602 nor the allele CDSN*TTC were significantly associated with psoriasis with the size of the sample studied. The genes and markers telomeric to HLA-C such as the microsatellite C1_4_4 (OR = 2.6, 95% CI = 1.4-4.7, p(c) = 0.018) the octamer transcription factor (OTF)-3 gene (OR = 2.6, 95% CI = 1.6-4.3, p(c) = 0.0001) and the alpha-helix coiled-coil rod homologue (HCR) gene (OR = 2.5, 95% CI = 1.3-4.5, p(c) = 0.004), however, were associated with the disease. These results suggest that a major psoriasis susceptibility gene is likely to be located within a region of 150 kb telomeric to HLA-C and centromeric to the CDSN gene.

Objective To analyze the HLA distribution in a population of individuals from Zambia in order to establish a possible relationship between the progression of human immunodeficiency virus (HIV) infection and the development of spondylarthropathy (SpA). Methods A large epidemiologic analysis of rheumatology patients living in Zambia was performed in order to identify those who had SpA. We selected 64 patients with SpA and found that 54 also had HIV type 1 (HIV-1) infection; only 10 were HIV negative. Additionally, we selected 57 HIV-infected individuals without SpA and 43 healthy controls. Among all of the HIV-1–infected patients, 25 SpA-positive and 24 SpA-negative patients were classified as slow progressors to acquired immunodeficiency syndrome (AIDS), and 8 SpA-positive and 26 SpA-negative patients were classified as rapid progressors. All patients were typed for HLA–B alleles. Results Of the 64 patients with SpA, HIV infection was observed in 54 (84%). The frequency of B*5703 was increased in patients who were SpA positive and HIV positive compared with patients who were SpA negative and HIV positive (P = 0.0002, odds ratio [OR] 8.28). Among patients who were slow progressors to AIDS, this allele was overrepresented in those with SpA compared with those without SpA (corrected P = 0.001, OR 26.25). Conclusion HLA–B*5703 seems to be a protective allele against the progression of HIV infection but could influence the increased incidence of SpA observed in this population.

The aim of this study was to investigate the association of MHC genes in the development of celiac disease (CD) and its diverse clinical forms in a Saharawi population.One hundred and twenty-five CD patients and 98 healthy controls were selected from the Saharawi refugee camps in Tindouf. All were investigated for the presence of antitransglutaminase 2 antibodies. Patients were divided into two groups according to their clinical manifestations: 70 typical and 55 atypical. Patients and controls were typed for HLA-B, DRB1, DQB1, and DQA1, and for MICA transmembrane polymorphism.The frequency of HLA-DQ2 in Saharawi controls was notably increased compared with other populations. No differences in the distribution of DQ2 in either group of patients were found. However, the haplotype B8/DR3/DQ2 was notably overrepresented in atypical patients compared to typical ones (pc= 0.001). The MICA-A5.1 allele was increased in atypical CD patients compared to those with typical forms (pc= 0.0006). Finally, we found that the increased frequency of MICA-A5.1 in the atypical group was independent of the linkage disequilibrium with B8/DR3/DQ2 haplotype (p= 0.02).The elevated prevalence of CD in Saharawi seems to be related to the high frequency of HLA-DQ2 in this population. However, the development of atypical or typical forms of the disease may be due to a gene or genes located in the class I side of the haplotype B8/DR3/DQ2, especially MICA. This appears not to be implicated in the susceptibility to CD but may play an important role in the development of the different forms of the disease.

We have studied the polymorphism of HLA class I in two West African Pygmy populations, namely, the Bakola from Cameroon and the Mbenzele from the Central African Republic. A unique number of HLA alleles and haplotypes showed specific patterns of these populations. In this study, we identify two alleles (B*37, B*41) and three haplotypes (A*30-B*37, A*66-B*41 and A*68-B*58) that appear to be 'private' or typical of Western Pygmies. These data reflect similarities with the AKA Pygmies from the Central African Republic. On the other hand, we failed to identify alleles that are found at high frequencies among other sub-Saharan populations (B*42, B*51). Allelic and haplotypic frequency distributions show differences between the two Pygmy groups, e.g. B*35 was very common in the Mbenzele but has been found to be absent in the Bakola. In contrast, B*53, which is found in the Bakola, has been found to be rare in the Mbenzele Pygmies. In order to analyse the genetic relationships of the Bakola and Mbenzele Pygmies with other sub-Saharan populations, HLA gene frequencies were subjected to the Neighbour-Joining tree analysis. The Mbenzele, Bakola and AKA were found to be relatively close to each other and isolated from other sub-African populations. However, both the genetic distances and the within-group variation suggests that the Bakola are more admixed with Bantu farmers than Mbenzele.

Recent evidence from several studies has suggested a genetic predisposition in the pathogenesis of ulcerative colitis (UC), which is especially related with major histocompatibility complex (MHC) genes. The aim of this study was to investigate the possible association of human leukocyte antigen (HLA-B, HLA-DR) and MHC class I chain-related-transmembrane (MICA-TM) polymorphism with the behavior and extension of UC. We selected 121 unrelated patients with UC. These were divided into two groups according to the extension of the disease: 31 patients with distal UC and 90 with wide extension UC; 116 blood donors were also selected as healthy controls, all of whom were typed for HLA-B, HLA-DR, and MICA-TM alleles. HLA-B7 was found to be overrepresented in distal UC patients compared with those with extensive UC (p(c) = 0.007, OR = 5.33) and healthy controls (p(c) = 0.03, OR = 4.09). The MICA-A5.1 allele was also increased in distal UC (p(c) = 0.015, OR = 3.82) when compared with extensive forms. These alleles are in strong linkage disequilibrium in our population. The MICA-A5 allele was significantly increased in extensive forms when compared with healthy controls(p(c) = 0.02, OR = 2.4). According to our results, MICA-A5.1 allele seems to be protective against extensive forms of UC, and MICA-A5 may condition a worse progression of the disease. These results are in agreement with other studies that suggest a similar role of such alleles in other diseases, such as insulin-dependent diabetes mellitus and celiac disease.

Objective Tumor necrosis factor-α (TNF-α) plays a key role in the inflammatory response and pathogenesis of Crohn’s disease (CD). TNF-α −308A polymorphism within the TNF-α gene promoter has been associated with enhanced TNF-α production in vitro. The aim of this study was to investigate the effect of TNF-α promoter polymorphism at −308 on the susceptibility and phenotypic expression of fistulizing CD.

Objective To investigate the contribution of HLA class I alleles in the susceptibility to primary ankylosing spondylitis (AS) in West African patients living in Togo. Methods A large epidemiologic analysis of 9,065 West African rheumatology patients living in Togo was performed in order to identify those who had AS. Eight Togolese patients with AS were identified. HLA was typed by polymerase chain reaction using sequence-specific oligonucleotide probes. DNA typing was also performed on a control population of 85 healthy subjects matched for ethnic background. Results A significant association between AS and B*14 was identified. This allele was found in 62.5% of the AS patients (odds ratio 69), but was carried by only 2% of the healthy controls. Analysis for B14 subtypes showed that B*1403 was the predominant allele in AS patients (odds ratio 171), and that this allele was absent in healthy controls. B27 was virtually absent, being observed in only 1 AS patient (B*2705). Conclusion HLA–B*1403 shows the B27 “supertype” motif and may exert an effect on AS susceptibility according to the arthritogenic peptide model. The association of B*1403 with AS has not previously been reported in either population.

Background and aims: Coeliac disease (CD) is an enteropathic disorder characterised by a strong association with major histocompatibility complex (MHC) heterodimer HLA-DQ2. It has been suggested that other HLA class I genes in combination with DQ may also contribute to CD susceptibility. The aim of this study was to investigate whether other candidate genes modify the risk of developing different clinical forms of CD. Patients and methods: We studied 133 Spanish coeliac patients, divided according to their clinical presentation into typical and atypical groups, and 116 healthy controls. All were typed by polymerase chain reaction-sequence specific primers (PCR-SSP) at HLA-B, DRB1, DQA1, and DQB1 loci and for exon 5 of the MHC class I chain related gene A (MICA). Results: No differences were found in the frequency of the DQA1*0501/DQB1*0201 heterodimer in either group. The risk of typical CD was significantly associated with the DR7/DQ2 haplotype (pc=0.02, odds ratio (OR)=3.4, ethiological fraction (EF)=0.4). Extended haplotype (EH) 8.1 (B8/DR3/DQ2) was found to be overrepresented in the atypical form compared with the typical form (pc=0.001, OR=4.19, EF=0.56). The trinucleotide repeat polymorphism MICA-A5.1 was found to be increased in the atypical group of patients compared with the typical group (pc=0.00006, OR=8.63, EF=0.81). This association was independent of linkage disequilibrium with EH8.1 as this was also found to be increased in EH8.1 negative atypical patients compared with the typical group (pc=0.004, OR=6.66, EF=0.56). Conclusions: Our results showed that the risk of developing typical forms of CD was associated with DR7/DQ2 haplotype, and the presence of B8/DR3/DQ2 was significantly increased in atypical patients. In these, the MICA-A5.1 allele confers an additive effect to the DR3/DQ2 haplotype that may modulate the development of CD.

We have characterized HLA-B27 alleles in a sample of the population from the Azores (n=46) with the aim of investigating the contribution of different subtypes to ankylosing spondylitis (AS). The study was carried out using PCR-SSOP and in some samples genomic sequencing was conducted. Some significant new finding have arisen from this study. First, B*2705,B*2702,B*2703,B*2707 and B*2708 alleles were found to be represented in this population. The polymorphism of B27 alleles found in a sample of the population from the Azores is higher than the Caucasian groups described. B*2703 and B*2707 have not previously been described to be represented in Caucasians and this could indicate admixtures with different populations of the world. In addition, the B*2708 allele was found to be associated with AS in a large family from the Azores. This association has not been previously reported in either ethnic group and needs to be confirmed in other population studies. This is of considerable interest since has only been described as a rare subtype underrepresented in the British population and has not been previously found to be associated with AS. B*2708 carries the sequence specifying the Bw6 epitope in contrast to most B27 alleles which carry a Bw4 sequence. Differences in this region (residues 77-83) can alter the F-pocket and affect T-cell recognition. The importance that these molecular changes can play in the pathogenesis of AS is discussed.