Centromeric AA motif in KIR as an optimal surrogate marker for precision definition of alloimmune reproductive failure.

Throughout pregnancy, the decidua is predominantly populated by NK lymphocytes expressing Killer immunoglobulin-like receptors (KIR) that recognize human leukocyte antigen-C (HLA-C) ligands from trophoblast cells. This study aims to investigate the association of KIR-HLA-C phenotypes in couples facing infertility, particularly recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), in comparison to a reference population and fertile controls. This observational, non-interventional retrospective case-control study included patients consecutively referred to our Reproductive Immunology Unit from 2015 to 2019. We analyzed the frequencies of KIR and HLA-C genes. As control groups, we analyzed a reference Spanish population for KIR analysis and 29 fertile controls and their male partners for KIR and HLA-C combinations. We studied 397 consecutively referred women with infertility and their male partners. Among women with unexplained RPL (133 women) and RIF (176 women), the centromeric (cen)AA KIR genotype was significantly more prevalent compared to the reference Spanish population (p = 0.001 and 0.02, respectively). Furthermore, cenAA was associated with a 1.51-fold risk of RPL and a 1.2-fold risk of RIF. Conversely, the presence of BB KIR showed a lower risk of reproductive failure compared to non-BB KIR (OR: 0.12, p < 0.001). Women and their partners with HLA-C1C1/C1C1 were significantly less common in the RPL-Group (p < 0.001) and RIF-Group (p = 0.002) compared to the control group. Moreover, the combination of cenAA/C1C1 in women with C1C1 partners was significantly higher in the control group than in the RPL (p = 0.009) and RIF (p = 0.04) groups, associated with a 5-fold increase in successful pregnancy outcomes. In our cohort, the cenAA KIR haplotype proved to be a more accurate biomarker than the classic AA KIR haplotype for assessing the risk of RPL and RIF, and might be particularly useful to identify women at increased risk among the heterogeneous KIR AB or Bx population. The classification of centromeric KIR haplotypes outperforms classical KIR haplotypes, making it a better indicator of potential maternal-fetal KIR-HLA-C mismatch in patients.

Adherencia a la vacunación COVID-19 en profesionales sanitarios: revisión exploratoria / Adherence to COVID-19 vaccination in health professionals: a scoping review

Introducción: Revisar la literatura científica relacionada con la adherencia a la vacunación COVID-19 entre los profesionales sanitarios y explorar las barreras y facilitadores que inclinan la balanza hacia la aceptación o hacia la vacilación de la vacunación contra la COVID-19.Métodos:Revisión exploratoria de los artículos recuperados en la base de datos bibliográfica MEDLINE (vía PubMed) hasta marzo de 2022. La ecuación de búsqueda se formuló mediante los descriptores “Occupational Groups”, “Vaccination”, “Coronavirus Infections”, “COVID-19 Vaccines” y “Treatment Adherence and Compliance”, utilizando también los Entry Terms relacionados y los filtros: «Humans» y «Adult: 19+ years». Para conocer el nivel de evidencia y su grado de recomendación se usaron las recomendaciones SIGN.Resultados:De las 135 referencias recuperadas, tras aplicar los criterios de inclusión y exclusión, se seleccionaron 27 artículos: 26 estudios descriptivos transversales y 1 estudio cualitativo. En 17 (62,96%) artículos se midió la aceptación, cuyos datos recopilados mostraron una aceptación moderada tomando como valor conforme un 70% de aceptación para frenar la pandemia por COVID-19. Y en 21 (77,78%) artículos que cuantificaron la vacilación se observaron valores de reticencia elevados, pero que, a largo plazo, seguían una tendencia a la baja. Además, se recopilaron las principales barreras para la vacunación contra la COVID-19, las cuales eran: preocupaciones acerca de la seguridad, eficacia, rápido desarrollo de las vacunas contra la COVID-19 y falta de información y confianza en ellas y los principales facilitadores: sexo masculino, haber sido vacunado anteriormente contra la gripe, ser médico, enfermero o trabajos afines en los que se tiene contacto con los pacientes. (AU)

Introduction: To review the scientific literature related to adherence to COVID-19 vaccination among healthcare professionals (HCPs) and to explore the barriers and facilitators that tip the balance towards acceptance or hesitancy of COVID-19 vaccination.Methods:Exploratory review of articles retrieved from the MEDLINE bibliographic database (via PubMed). through March 2022.The search equation was formulated using the descriptors: “Occupational Groups”,”Vaccination”, “Coronavirus Infections”, “COVID-19 Vaccines” and “Treatment Adherence and Compliance”, also using the related Entry Terms and the filters: “Humans” and “Humans”.SIGN recommendations were used to determine the level of evidence and degree of recommendation.Results:Of the 135 references retrieved, after applying the inclusion and exclusion criteria, 27 articles were selected: 26 cross-sectional descriptive studies and 1 qualitative study. The values of acceptance to COVID-19 vaccination ranged from a minimum of 37.2% to a maximum of 80.7%. Twenty-one (77.78%) articles quantified hesitancy, with high reluctance values, but with a long-term downward trend. The main barriers to COVID-19 vaccination were: concerns about safety, efficacy, rapid development of COVID-19 vaccines and lack of information and confidence in them and the main facilitators: male sex, having been previously vaccinated against influenza, being a doctor, nurse or related jobs where one has contact with patients. (AU)

Where and when should natural killer cells be tested in women with repeated implantation failure?

The aim of this study was to identify the candidates for natural killer (NK) testing and to define the best methodology. For this purpose a prospective study was performed on 73 women with repeated implantation failure (RIF). RIF was considered to exist in patients not achieving clinical pregnancy after three transfers with at least one good-quality embryo. Idiopathic RIF was considered to exist in patients in whom thrombophilia, hysteroscopy and endometrial culture were normal, and no chromosomal factor was suspected. Thirty-two of the 73 patients were considered to have idiopathic RIF, and 17 fertile women with children were taken as controls. Immunohistochemical staining for endometrial CD56+ and blood CD56+ or CD16+ NK cells measured using flow cytometry were compared during the mid-luteal phase in both patients and controls. Seventeen out of the 32 patients with idiopathic RIF and only one of the controls had >250 CD56 cells per high power field 400× in endometrial biopsy (p<0.001). The percentage of blood NK cells out of the total lymphocyte population was higher in women with idiopathic RIF (13.4±1.2%; range, 2.63-29.01) than in controls (8.4±0.7%; range, 5.72-13.28; p=0.026). There was a positive correlation between blood and endometrial CD56 cells (ρ=0.707; p<0.001). No significant differences were found between patients with other types of RIF and controls. This study suggested that testing for NK cells might be useful in women with idiopathic RIF during the mid-luteal phase.

Experience in IVIg therapy for selected women with recurrent reproductive failure and NK cell expansion.

PROBLEM: Recurrent reproductive failure (RRF) has been associated with expansion of circulating NK cells, key cells for maternal tolerance, decidual vasculogenesis and embryo growth. This study reports our experience in intravenous immunoglobulin (IVIg) therapy of a large cohort of women with RRF with expanded circulating NK and/or NKT-like cells (blood NKT cells are a heterogeneous subset of T cells that share properties of both T cells and NK cells). METHOD OF STUDY: Observational study of RRF women with NK or NKT-like expansion (>12% or 10% cutoff levels of total lymphocytes, respectively), treated with IVIg for the next gestation. RESULTS: By multivariant logistic regression analysis after adjusting for age, NK cells subsets and other therapies, IVIg significantly improved the live birth rate to 96.3% in women with recurrent miscarriage (RM) compared with 30.6% in case not receiving IVIg (P < 0.0001). In women with recurrent implantation failure (RIF), in comparison with women not receiving IVIg, treatment increased the pregnancy rate from 26.2 to 93.8% (P ≤ 0.0001) and the live birth rate from 17.9 to 80.0% in RIF (P ≤ 0.0001). CONCLUSIONS: Immunomodulation with IVIg in our selected group of RRF patients with immunologic alterations enhanced clinical pregnancy and live birth rates. Our results may facilitate the design of future clinical trials of IVIg in this pathology.