The past, present, and future in antinuclear antibodies (ANA)

Autoantibodies are a hallmark of autoimmunity and, specifically, antinuclear antibodies (ANAs) are the most relevant autoantibodies present in systemic autoimmune rheumatic diseases (SARDs). Over the years, different methods from LE cell to HEp-2 indirect immunofluorescence (IIF), solid-phase assays (SPAs), and finally multianalyte technologies have been developed to study ANA-associated SARDs. All of them provide complementary information that is important to provide the most clinically valuable information. The identification of new biomarkers together with multianalyte platforms will help close the so-called "seronegative ga" and to correctly classify and diagnose patients with SARDs. Finally, artificial intelligence and machine learning is an area still to be exploited but in a next future will help to extract patterns within patient data, and exploit these patterns to predict patient outcomes for improved clinical management

Utilidad de la medición de adenosina 5'-trifosfato intracelular en células CD4+ en trasplante renal

ImmuKnow is an in vitro diagnosis method that uses patient samples of whole blood polyclonally stimulated with phytohaemagglutinin. It also measures adenosine triphosphate (ATP) production by CD4+ T cells. The test aims to offer an objective and overall measurement of each individual's cellular immune response. The assay was designed with the idea of individually monitoring the immunosuppression administered to transplant patients. At the same time, it aims to help achieve a balance as a way of avoiding immunosuppression excess and the associated adverse effects (infections, cancer, etc.) or an immunosuppression defect and the subsequent risk of allograft rejection. The majority of studies that have evaluated its clinical usefulness display great diversity in terms of patient recruitment, the immunosuppressant treatment received, the clinical variables analysed and, above all, the time between performing ImmuKnow and the evaluated clinical event. The most consistent data show that this assay on CD4+ T cell functioning is useful for predicting the risk of infection in renal transplant patients. However, its use as a rejection risk indicator is unclear. Lastly, given the great variability of immune response amongst individuals and that of existing publications, it can be deduced that the isolated ImmuKnow value does not have diagnostic capacity and only individual serial monitoring could provide definitive assistance in clinical decision making and immunosuppressant treatment changes. Other aspects of ImmuKnow application in the clinical routine, such as assay cycles, require randomised prospective studies for more comprehensive information.ImmuKnow® es un método diagnóstico in vitro que emplea sangre completa del paciente estimulada policlonalmente con fitohemaglutinina y mide la producción de adenosina 5'-trifosfato (ATP) por las células T CD4+. La prueba tiene como objetivo proporcionar una medida objetiva y global de la respuesta inmunitaria celular de cada individuo. El ensayo se diseñó con la idea de monitorizar la inmunosupresión administrada al paciente trasplantado de forma individualizada intentando ayudar a conseguir el equilibrio para evitar un exceso de inmunosupresión con los efectos adversos que conlleva (infecciones, cáncer, etc.) o un defecto de la inmunosupresión con el consiguiente riesgo de rechazo del aloinjerto. La mayoría de los trabajos que han evaluado su utilidad clínica muestra una gran diversidad en cuanto al modo de reclutamiento de los pacientes, el tratamiento inmunosupresor recibido, las variables clínicas analizadas y, sobre todo, el tiempo entre la realización de ImmuKnow® y el evento clínico evaluado. Los datos más consistentes muestran que este ensayo de función de las células T CD4+ resulta útil para predecir el riesgo de infección en trasplantados renales. Sin embargo, no está claro su empleo como marcador de riesgo de rechazo. Por último, dada la enorme variabilidad de la respuesta inmunitaria entre individuos y las publicaciones existentes, se deduce que un valor aislado de ImmuKnow® no tiene capacidad diagnóstica y solo un seguimiento seriado individualizado ayudaría más definitivamente a tomar decisiones clínicas y de cambios en el tratamiento inmunosupresor. Otros aspectos en relación con la aplicación de ImmuKnow® en la rutina clínica, como por ejemplo la periodicidad de la realización de la prueba, precisan estudios prospectivos aleatorizados para una más completa información

Differentiation of autoimmune pancreatitis from pancreas cancer: utility of anti-amylase and anti-carbonic anhydrase II autoantibodies.

Purpose: To investigate the utility of different combinations of serum anti-carbonic anhydrase II antibodies (CA II Abs), anti-α amylase antibodies (AMY-α Abs) and IgG4 levels for the diagnosis of autoimmune pancreatitis (AIP). Methods: We recruited 93 patients with clinical suspicion for AIP and 94 patients as control groups between June 2003 and October 2009. Serum antibodies were measured using homemade enzyme linked immunosorbent assay and IgG4 levels were determined by nephelometry. Results: Both CA-II Abs and AMY-α Abs had the highest sensitivity (83%) although AMY-α Abs (89%) were more specific than CA-II Abs (75%). The presence of increased IgG4 levels was the most specific serological marker (94%), but it had the lowest sensitivity (58%). The combination of the three serological markers altogether had the highest specificity (99%) and positive predictive value (PPV) (86%), but they had a rather low sensitivity (50%). When we combined CA-II Abs and AMY-α Abs without IgG4 levels, we got the highest sensitivity (75%) and negative predictive value (98%) but the specificity and the PPV decreased to 93 and 50%, respectively. Importantly, AMY-α Abs were not detected in pancreas cancer. Conclusions: The presence of serum CA-II and AMY-α Abs with increased IgG4 is useful in the differential diagnosis of AIP from pancreatic cancer

Review: Ischemia Reperfusion Injury?A Translational Perspective in Organ Transplantation

Thanks to the development of new, more potent and selective immunosuppressive drugs together with advances in surgical techniques, organ transplantation has emerged from an experimental surgery over fifty years ago to being the treatment of choice for many end-stage organ diseases, with over 139,000 organ transplants performed worldwide in 2019. Inherent to the transplantation procedure is the fact that the donor organ is subjected to blood flow cessation and ischemia during harvesting, which is followed by preservation and reperfusion of the organ once transplanted into the recipient. Consequently, ischemia/reperfusion induces a significant injury to the graft with activation of the immune response in the recipient and deleterious effect on the graft. The purpose of this review is to discuss and shed new light on the pathways involved in ischemia/reperfusion injury (IRI) that act at different stages during the donation process, surgery, and immediate post-transplant period. Here, we present strategies that combine various treatments targeted at different mechanistic pathways during several time points to prevent graft loss secondary to the inflammation caused by IRI

The Crosstalk between Hypoxia and Innate Immunity in the Development of Obesity-Related Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) has become a major health issue in western countries in parallel with the dramatic increase in the prevalence of obesity and all obesity related conditions, including respiratory diseases as obstructive sleep apneahypopnea syndrome (OSAHS). Interestingly, the severity of the liver damage in obesity-relatedNAFLD has been associatedwith the concomitant presence of OSAHS. In the presence of obesity, the proinflammatory state in these patients together with intermittent episodes of hypoxia, characteristic of OSAHS pathogenesis,may lead to an enhanced inflammatory response mediated by a positive feedback loop mechanism that implicates HIF-1 and NF????.Thus, the severity of liver involvement in obese NAFLD patients with a concomitant diagnosis of OSAHS could be explained. In this review, we focus on the molecularmechanisms underlying the hepatic response to chronic intermittent hypoxia and its interaction with innate immunity in obesity-related NAFLD

Socio-economic factors do also matter: comments on the article "can climatic factors explain the differences in COVID-19 incidence and severity across the SPANISH regions?: an ecological study"

Phosri et al., commented on our previous study about the influence of climate variables at the beginning of the SARS-CoV-2 pandemic in Spain. They showed the impact of the association of gross domestic product (GDP) with the cumulative COVID-19 incidence per 105 inhabitants in our country and the rise of several methodologic issues. Here we discussed the main advantages and disadvantages of ecological studies and we advocate to test the hypothesis created in this type of studies using individual-level research designs

Can climatic factors explain the differences in COVID-19 incidence and severity across the Spanish regions?: An ecological study

Background: Environmental factors play a central role in seasonal epidemics. SARS-CoV-2 infection in Spain has shown a heterogeneous geographical pattern This study aimed to assess the influence of several climatic factors on the infectivity of SARS-CoV-2 and the severity of COVID-19 among the Spanish Autonomous Communities (AA.CC.). Methods: Data on coronavirus infectivity and severity of COVID-19 disease, as well as the climatic variables were obtained from official sources (Ministry of Health and Spanish Meteorological Agency, respectively). To assess the possible influence of climate on the development of the disease, data on ultraviolet radiation (UVR) were collected during the months before the start of the pandemic. To analyze its influence on the infectivity of SARS-CoV-2, data on UVR, temperature, and humidity were obtained from the months of highest contagiousness to the peak of the pandemic. Results: From October 2019 to January 2020, mean UVR was significantly related not only to SARS-CoV-2 infection (cumulative incidence -previous 14 days- × 105 habitants, rho = - 0.0,666; p = 0.009), but also with COVID-19 severity, assessed as hospital admissions (rho = - 0.626; p = 0.017) and ICU admissions (rho = - 0.565; p = 0.035). Besides, temperature (February: rho = - 0.832; p < 0.001 and March: rho = - 0.904; p < 0.001), was the main climatic factor responsible for the infectivity of the coronavirus and directly contributed to a different spread of SARS-CoV-2 across the Spanish regions. Conclusions: Climatic factors may partially explain the differences in COVID-19 incidence and severity across the different Spanish regions. The knowledge of these factors could help to develop preventive and public health actions against upcoming outbreaks of the disease

Clinical significance of donor-specific human leukocyte antigen antibodies in liver transplantation

Antibody-mediated rejection (AMR) caused by donorspecific anti-human leukocyte antigen antibodies (DSA) is widely accepted to be a risk factor for decreased graft survival after kidney transplantation. This entity also plays a pathogenic role in other solid organ transplants as it appears to be an increasingly common cause of heart graft dysfunction and an emerging issue in lung transplantation. In contrast, the liver appears relatively resistant to DSA-mediated injury. This “immune-tolerance” liver property has been sustained by a low rate of liver graft loss in patients with preformed DSA and by the intrinsic liver characteristics that favor the absorption and elimination of DSA; however, alloantibody-mediated adverse consequences are increasingly being recognized, and several cases of acute AMR after ABO-compatible liver transplant (LT) have been reported. Furthermore, the availability of new solid-phase assays, allowing the detection of low titers of DSA and the refinement of objective diagnostic criteria for AMR in solid organ transplants and particularly in LT, have improved the recognition and management of this entity. A cost-effective strategy of DSA monitoring, avoidance of class ? human leukocyte antigen mismatching, judicious immunosuppression attached to a higher level of clinical suspicion of AMR, particularly in cases unresponsive to conventional antirejection therapy, can allow a rational approach to this threat

Heparan sulfate differences in rheumatoid arthritis versus healthy sera

Heparan sulfate (HS) is a complex and highly variable polysaccharide, expressed ubiquitously on the cell surface as HS proteoglycans (HSPGs), and found in the extracellular matrix as free HS fragments. Its heterogeneity due to various acetylation and sulfation patterns endows a multitude of functions. In animal tissues, HS interacts with a wide range of proteins to mediate numerous biological activities; given its multiple roles in inflammation processes, characterization of HS in human serum has significant potential for elucidating disease mechanisms. Historically, investigation of HS was limited by its low concentration in human serum, together with the complexity of the serum matrix. In this study, we used a modified mass spectrometry method to examine HS disaccharide profiles in the serum of 50 women with rheumatoid arthritis (RA), and compared our results to 51 sera from healthy women. Using various purification methods and online LC–MS/MS, we discovered statistically significant differences in the sulfation and acetylation patterns between populations. Since early diagnosis of RA is considered important in decelerating the disease's progression, identification of specific biomolecule characterizations may provide crucial information towards developing new therapies for suppressing the disease in its early stages. This is the first report of potential glycosaminoglycan biomarkers for RA found in human sera, while acknowledging the obvious fact that a larger population set, and more stringent collection parameters, will need to be investigated in the future.The authors gratefully acknowledge the financial support provided by the National Institutes of Health (Grant GM 47356)

Contraespacios públicos. Procesos y miradas desde Oriente

Desde mediados del siglo pasado ya era posible intuir que los procesos relativos a la democracia de masas tendrían sus repercusiones. La ciudad va transformándose poco a poco en el peligroso y anodino escenario de lo postpolítico, entendiendo éste como el marco global desarrollado en las últimas décadas por autores como Jacques Rancière o Slavoj Žižek. Precisamente desde esta lógica son las estructuras económicas las que controlan la actividad política y social, buscando eliminar toda diferencia o conflicto interno mediante consensos creados de forma artificial y contraria a lo que se entiende por auténtica política. Al contemplar las nuevas formas de urbanismo, vinculadas en muchas ocasiones a un control casi militar de la población e impregnadas de una obsesión exacerbada por incrementar el potencial económico de la ciudad como ente competitivo dentro de un mercado global, podemos afirmar que una espacialización -incluso de una territorialización- de lo postpolítico no es ya algo que se nos escape en el tiempo. De nuevo la arquitectura y el urbanismo como disciplinas del espacio parecen quedar abocadas a su viejo papel de instrumentos organizadores. Ante esta situación, surge la necesidad de posicionarse, detectar las formas de espacialización postpolíticas y, sobre todo, prestar atención a las posibilidades de espacios políticos emergentes. Dado que las posibilidades son infinitas, se hará especial énfasis en situaciones políticas determinadas y localizadas en Oriente, ya que el arco que trazan resulta aún bastante desconocido, o quizás poco asimilado, por determinadas áreas de pensamiento occidental, lo que no significa que sean menos reveladoras: más bien al contrario, completan la imagen que tenemos del mundo, e incluso de nosotros mismos. No es casualidad, por tanto, que el presente trabajo busque conclusiones y formas de actuar en tres ciudades en un principio lejanas a nuestro ámbito occidental más próximo –Pekín, Varsovia, Estambul- y desde temporalidades diferentes, ya que contemplando su reflejo (y el nuestro propio, que su superficie nos devuelve) estaremos reconociendo parte de ese “nosotros” que muchas veces resulta desconocido, o pasa desapercibido por encontrarse, precisamente, demasiado lejos. De este modo, se explorarán las condiciones del contraespacio desde su vertiente política, siendo el espacio, y no el tiempo, el elemento principal de concatenación.Ayudas para realizar congresos y reuniones científicas con proyección internacional. (III.1)-(Conv. 2013. Universidad de Sevilla