Anticuerpos antifosfolípido no convencionales como marcadores de disfunción endotelial residual en mujeres con preeclampsia

RESUMEN: La preeclampsia se encuentra asociada a un elevado riesgo cardiovascular futuro de las mujeres que la han padecido. El presente trabajo plantea que el desarrollo de preeclampsia en mujeres sin criterios de síndrome antifosfolípido, se encuentra asociado a una respuesta autoinmune que se puede objetivar mediante la detección de anticuerpos antifosfolípido no convencionales. Estos anticuerpos podrían asociarse a la disfunción endotelial generalizada que se origina en la preeclampsia y afectar negativamente al riesgo cardiovascular futuro de la madre, lo que podría objetivarse mediante el análisis de parámetros de afectación vascular como la velocidad de onda de pulso (VOP) y el índice tobillo brazo (ITB). Para ello, se llevó a cabo, tres meses después del parto, la determinación de anticuerpos antifosfolípido no convencionales, VOP e ITB en un grupo de mujeres con preeclampsia y un grupo control de mujeres cuya gestación se desarrolló sin trastornos hipertensivos del embarazo. El análisis estadístico mostró que las mujeres con preeclampsia presentan una prevalencia de anticuerpos antifosfatidilserina/protrombina IgM (aPS/PT IgM) hasta tres veces superior a la de mujeres con embarazos normales. Igualmente, se identificó una importante asociación de los anticuerpos aPS/PT IgM con el desarrollo y severidad de la preeclampsia, así como una fuerte correlación lineal positiva con la VOP y una correlación moderada e inversa con el ITB. Por ello, se propone que en aquellas pacientes que desarrollan preeclampsia, la positividad postparto para anticuerpos aPS/PT IgM se asocia con la existencia de disfunción endotelial definida como presencia de valores alterados de VOP o ITB, lo cual podría constituir un biomarcador de utilidad para la estratificación del riesgo cardiovascular, ayudando a la identificación de mujeres que podrían beneficiarse de una monitorización más estrecha.ABSTRACT: Preeclampsia is associated with a high future cardiovascular risk in women who have suffered this disease. The present work, suggests that the development of preeclampsia in women without criteria of antiphospholipid syndrome is associated with an autoimmune response that can be demonstrated by detecting unconventional antiphospholipid antibodies. These antibodies could be associated with the generalized endothelial dysfunction originated in preeclampsia and affect negatively to the future cardiovascular risk of the mother. Cardiovascular risk could be identified by analyzing parameters of vascular involvement such as pulse wave velocity (PWV) and ankle brachial index (ABI). For this purpose, three months after delivery, unconventional antiphospholipid antibodies, PWV and ABI were determined in a group of women with preeclampsia and in a control group of women whose gestation was developed without hypertensive disorders of pregnancy. Statistical analysis showed that women with preeclampsia have a prevalence of antiphosphatidylserine/prothrombin IgM antibodies (IgM aPS/PT) three times higher than those women with normal pregnancies. Likewise, an important association of IgM aPS/PT antibodies with the development and severity of preeclampsia was identified, as well as a strong positive linear correlation with PWV and a moderate and inverse correlation with ABI. Therefore, it is proposed that in those patients who develop preeclampsia, postpartum positivity for IgM aPS/PT antibodies is associated with the existence of endothelial dysfunction defined as altered values of PWV or ABI. This finding could constitute a useful biomarker for cardiovascular risk stratification, helping to identify women who could benefit from closer monitoring

COVID-19-related collapse of transplantation systems: A heterogeneous recovery?

The coronavirus disease‐2019 (COVID‐19) pandemic has pushed healthcare systems to the limit worldwide. Hospital resources have been compromised, especially in intensive care units (ICUs). Regarding that, some nephrologists have alerted about the potential shortages of our ability to deliver kidney replacement therapy to all patients who need it (1). Simultaneously, two reports have highlighted the collapse of organ transplantation figures in several countries such as France (91%), the US (51%) and Spain (87%), mainly due to a reduction in the number of transplants from deceased donors

High Pretransplant BAFF Levels and B-cell Subset Polarized towards a Memory Phenotype as Predictive Biomarkers for Antibody-Mediated Rejection

Antibody-mediated rejection (AbMR) is one of the leading causes of graft loss in kidney transplantation and B cells play an important role in the development of it. A B-cell activating factor (BAFF) is a cytokine involved in B cell ontogeny. Here, we analyzed whether B cell maturation and the e ect of B cell soluble factors, such as BAFF could be involved in AbMR. Serum BAFF levels and B and T cell subpopulations were analyzed 109 kidney transplant patients before transplantation and at 6 and 12 months after kidney transplantation. Pretransplant serum BAFF levels as well as memory B cell subpopulations were significantly higher in those patients who su ered clinical AbMR during the first 12 months after kidney transplantation. Similar results were observed in the prospective analysis of patients with subclinical antibody-mediated rejection detected in the surveillance biopsy performed at 12 months after kidney transplantation. A multivariate analysis confirmed the independent role of BAFF in the development of AbMR, irrespective of other classical variables. Pretransplant serum BAFF levels could be an important non-invasive biomarker for the prediction of the development of AbMR and posttransplant increased serum BAFF levels contribute to AbMR

IgA vasculitis: influence of CD40, BLK and BANK1 gene polymorphisms

CD40, BLK and BANK1 genes involved in the development and signaling of B-cells are identified as susceptibility loci for numerous inflammatory diseases. Accordingly, we assessed the potential influence of CD40, BLK and BANK1 on the pathogenesis of immunoglobulin-A vasculitis (IgAV), predominantly a B-lymphocyte inflammatory condition. Three genetic variants within CD40 (rs1883832, rs1535045, rs4813003) and BLK (rs2254546, rs2736340, rs2618476) as well as two BANK1 polymorphisms (rs10516487, rs3733197), previously associated with inflammatory diseases, were genotyped in 382 Caucasian patients with IgAV and 955 sex- and ethnically matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of CD40, BLK and BANK1 when IgAV patients and healthy controls were compared. Similar results were found when CD40, BLK and BANK1 genotypes or alleles frequencies were compared between patients with IgAV stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Moreover, no CD40, BLK and BANK1 haplotype differences were disclosed between patients with IgAV and healthy controls and between patients with IgAV stratified according to the clinical characteristics mentioned above. Our findings indicate that CD40, BLK and BANK1 do not contribute to the genetic background of IgAV.Funding: This study was supported by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” (grants PI18/00042 and PI21/00042) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain). D.P.-P. is a recipient of a Río Hortega program fellowship from the ISCIII, co-funded by the European Social Fund (ESF, “Investing in your future”) (grant number CM20/00006). F.G. is supported by funds of the RICORS Program from ISCIII, co-funded by the European Union (grant number RD21/0002/0025). V.P.-C. is supported by funds of PI18/00042. S.R.-M. is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, co-funded by the European Regional Development Fund (ERDF)). O.G. is a staff member of Xunta de Galicia (Servizo Galego de Saude (SERGAS)) through a research-staff stabilization contract (ISCIII/SERGAS) and his work is funded by ISCIII and the European Union FEDER fund (grant numbers RD16/0012/0014 (RIER) and PI17/00409). He is a beneficiary of project funds from the Research Executive Agency (REA) of the European Union in the framework of MSCA-RISE Action of the H2020 Program, project 734899—Olive-Net. R.L.-M. is a recipient of a Miguel Servet type II program fellowship from the ISCIII, co-funded by ESF (“Investing in your future”) (grant number CPII21/00004). Acknowledgments: We are indebted to the patients and healthy controls for their essential collaboration on this study. We also thank the National DNA Bank Repository (Salamanca) for supplying part of the control samples

Mucosal Immune Defence Gene Polymorphisms as Relevant Players in the Pathogenesis of IgA Vasculitis?

ITGAM–ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM–ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis

IgA Vasculitis: Influence of CD40, BLK and BANK1 Gene Polymorphisms

CD40, BLK and BANK1 genes involved in the development and signaling of B-cells are identified as susceptibility loci for numerous inflammatory diseases. Accordingly, we assessed the potential influence of CD40, BLK and BANK1 on the pathogenesis of immunoglobulin-A vasculitis (IgAV), predominantly a B-lymphocyte inflammatory condition. Three genetic variants within CD40 (rs1883832, rs1535045, rs4813003) and BLK (rs2254546, rs2736340, rs2618476) as well as two BANK1 polymorphisms (rs10516487, rs3733197), previously associated with inflammatory diseases, were genotyped in 382 Caucasian patients with IgAV and 955 sex- and ethnically matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of CD40, BLK and BANK1 when IgAV patients and healthy controls were compared. Similar results were found when CD40, BLK and BANK1 genotypes or alleles frequencies were compared between patients with IgAV stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Moreover, no CD40, BLK and BANK1 haplotype differences were disclosed between patients with IgAV and healthy controls and between patients with IgAV stratified according to the clinical characteristics mentioned above. Our findings indicate that CD40, BLK and BANK1 do not contribute to the genetic background of IgAV

New oral anticoagulants in patients with chronic kidney disease

Patients with chronic kidney disease (CKD) develop bleeding and thrombotic tendencies, so the indication of anticoagulation at the onset of atrial fibrillation (AF) is complex. AF is the most common chronic cardiac arrhythmia, and thromboembolism and ischaemic stroke in particular are major complications. In recent years, new oral anticoagulant drugs have been developed, and they have shown superiority over the classical AVK in preventing stroke, systemic embolism and bleeding risk, constituting an effective alternative to those resources