Prevalence of anti-HLA antibodies among live related renal transplant recipients: A retrospective observational study from a tertiary healthcare Center in India.

Detection of anti-HLA antibodies is crucial for pre-transplant histocompatibility testing, donor selection, and graft survival. The aim of this study was to evaluate the spectrum of anti-HLA antibodies among live related renal transplant recipients from one of the largest transplant centers in north India. In this study, retrospective data of transplant workup done in past four years were analyzed using GraphPad Prism 9 Version 9.2.0 (La Jolla, CA, USA). All samples received for pre-transplant work-up if showed positive screening results underwent Luminex single antigen bead (L-SAB) assay. Antibodies identified on L-SAB were evaluated for their specificity and the strength of their mean florescence intensity (MFI). A total of 1250 renal transplant samples were included for analysis. Out of these, 458 (36.64 %) samples were found positive in screening tests algorithm. All 458 samples were further analyzed for both class I and class II HLA antibodies by Luminex single antigen bead (L-SAB) assay. In this study, we observed that anti-A*24:01, anti-B*15:01 and anti-C*07*01 were the three most prevalent anti-HLA antibodies identified against HLA-class I antigens. However, anti-DRB1*11:01, anti-DQA1*05:01-DQB1*03:01 and anti-DPA1*02:01-DPB1*17:01 were the most common anti-HLA antibodies identified against HLA-class II antigen. Furthermore, our study found a significant association between anti-HLA class I antibody and the history of pregnancy. However, in re-transplant cases, we observed the presence of antibodies both against HLA class I and II antigens. For a transplant center, it is of utmost importance to have comprehensive knowledge about the prevalence of HLA antibodies, their MFI, and their association with various sensitization events. This study may immensely help transplant communities in selecting appropriate prospective organ donors, planning desensitization regimes, managing recipients' care and predicting transplant outcomes in live related renal transplantation.

Pandey P ，Pande A ，Marik A ，Devra AK ，Sinha VK ，Bhatt AP ，Setya D ，Mishra S ，Jha S ... -  《-》

Sex and gender as predictors for allograft and patient-relevant outcomes after kidney transplantation.

Sex, as a biological construct, and gender, defined as the cultural attitudes and behaviours attributed by society, may be associated with allograft loss, death, cancer, and rejection. Other factors, such as recipient age and donor sex, may modify the association between sex/gender and post-transplant outcomes. We sought to evaluate the prognostic effects of recipient sex and, separately, gender as independent predictors of graft loss, death, cancer, and allograft rejection following kidney or simultaneous pancreas-kidney (SPK) transplantation. We aimed to evaluate this prognostic effect by defining the relationship between recipient sex or gender and post-transplantation outcomes identifying reasons for variations between sexes and genders, and then quantifying the magnitude of this relationship. We searched MEDLINE and EMBASE databases from inception up to 12 April 2023, through contact with the Cochrane Kidney and Transplant Information Specialist, using search terms relevant to this review and no language restrictions. Cohort, case-control, or cross-sectional studies were included if sex or gender were the primary exposure and clearly defined. Studies needed to focus on our defined outcomes post-transplantation. Sex was defined as the chromosomal, gonadal, and anatomical characteristics associated with the biological sex, and we used the terms "males" and "females". Gender was defined as the attitudes and behaviours that a given culture associates with a person's biological sex, and we used the terms "men" and "women". Two authors independently assessed the references for eligibility, extracted the data and assessed the risk of bias using the Quality in Prognosis Studies (QUIPS) tool. Whenever appropriate, we performed random-effects meta-analyses to estimate the mean difference in outcomes. The outcomes of interest included the Standardised Outcomes in Nephrology-Kidney Transplant (SONG-Tx) core outcomes, allograft loss, death, cancer (overall incidence and site-specific) and acute or chronic graft rejection. Fifty-three studies (2,144,613 patients; range 59 to 407,963) conducted between 1990 and 2023 were included. Sixteen studies were conducted in the Americas, 12 in Europe, 11 in the Western Pacific, four in the Eastern Mediterranean, three in Africa, two in Southeast Asia, and five across multiple regions. All but one study focused on sex rather than gender as the primary exposure of interest. The number identified as male was 54%; 49 studies included kidney transplant recipients, and four studies included SPK transplant recipients. Twenty-four studies included adults and children, 25 studies included only adults, and four studies included only children. Data from 33 studies were included in the meta-analyses. Among these, six studies presented unadjusted hazard ratios (HRs) that assessed the effect of recipient sex on kidney allograft loss. The other studies reported risk ratios (RRs) for the pre-defined outcomes. Notably, the decision to restrict the meta-analyses to unadjusted estimates arose from the variation in covariate adjustment methods across studies, lacking a common set of adjusted variables. Only three studies considered the modifying effect of recipient age on graft loss or death, which is likely crucial to evaluating sex differences in post-transplant outcomes. No studies considered the modifying effect of recipient age on cancer incidence or allograft rejection risk. In low certainty evidence, compared with male recipients, being female may make little or no difference in kidney allograft loss post-transplantation (7 studies, 5843 patients: RR 0.91, 95% CI 0.73 to 1.12; I2 = 73%). This was also observed in studies that included time-to-event analyses (6 studies, 238,937 patients; HR 1.07, 95% CI, 0.95 to 1.20; I2 = 44%). Two recent large registry-based cohort studies that considered the modifying effects of donor sex and recipient age showed that female recipients under 45 years of age had significantly higher graft loss rates than age-matched male recipients in the setting of a male donor. In contrast, female recipients 60 years and older had lower graft loss rates than age-matched male recipients, regardless of donor sex. Compared with male recipients, being female may make little or no difference in death up to 30 years post-transplantation; however, the evidence is very uncertain (13 studies, 60,818 patients: RR 0.94, 95% CI 0.81 to 1.09; I2 = 92%). Studies that considered the modifying effect of recipient age and donor sex showed that female recipients had a higher excess death risk than males under 45 years of age in the setting of a male donor. Compared with male recipients, being female may make little or no difference in cancer incidence up to 20 years post-transplantation; however, the evidence is very uncertain (7 studies, 25,076 patients; RR 0.84, 95% CI 0.70 to 1.01; I2 = 60%). Compared with male recipients, being female may make little or no difference in the incidence of acute and chronic kidney allograft rejection up to 15 years post-transplantation (9 studies, 6158 patients: RR 0.89, 95% CI 0.75 to 1.05; I2 =54%; low certainty evidence). One study assessed gender and reported that when compared with men, women experienced better five-year survival in high (HR 0.71, 95% CI 0.59 to 0.87) and middle-income areas (HR 0.82, 95% CI 0.74 to 0.92), with no difference in low-income areas (HR 0.85, 95% CI 0.72 to 1.01). There was considerable uncertainty regarding any association between sex or gender and post-transplant patient-relevant outcomes. This was primarily due to clinical and methodological heterogeneity. The observed clinical heterogeneity between studies could be attributed to diverse patient characteristics within sample populations. As a result of limited sex-stratified demographic data being provided, further investigation of this heterogeneity was constrained. However, factors contributing to this finding may include recipient age, donor age, types, and sex. Methodological heterogeneity was noted with the interchangeable use of sex and gender, outcome misclassification, the use of different measures of effects, inconsistent covariate profiles, and disregard for important effect modification. There is very low to low certainty evidence to suggest there are no differences in kidney and pancreas allograft survival, patient survival, cancer, and acute and chronic allograft rejection between male and female kidney and SPK transplant recipients.

Jayanti S ，Beruni NA ，Chui JN ，Deng D ，Liang A ，Chong AS ，Craig JC ，Foster B ，Howell M ，Kim S ，Mannon RB ，Sapir-Pichhadze R ，Scholes-Robertson NJ ，Strauss AT ，Jaure A ，West L ，Cooper TE ，Wong G ... -  《Cochrane Database of Systematic Reviews》

Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling.

Elwenspoek MM ，Thom H ，Sheppard AL ，Keeney E ，O'Donnell R ，Jackson J ，Roadevin C ，Dawson S ，Lane D ，Stubbs J ，Everitt H ，Watson JC ，Hay AD ，Gillett P ，Robins G ，Jones HE ，Mallett S ，Whiting PF ... -  《-》

Human leukocyte antigen mismatch and circulating donor-specific antibodies predict graft loss after kidney transplantation: A retrospective study from Campania region - Italy.

Donor-specific antibodies (DSA) are an established biomarker predicting antibody-mediated rejection, as the leading cause of graft loss after kidney transplantation. Furthermore, human leukocyte antigen (HLA) matching offers a more precise assessment of donor-recipient HLA compatibility and may prevent more effectively sensitization against allograft tissue. Indeed, increased number of HLA mismatches (MM) is significantly associated with a higher risk of immunological rejection, de novo DSA (dnDSA) development, and graft failure. Over the last decade, a comprehensive approach to optimize kidney matching and monitor transplant recipients for acute and chronic graft dysfunction was the goal for the success of the kidney transplantation. In our long-term retrospective study, we have found that pre- and post-transplantation HLA antibodies were significantly associated with de novo dnDSA occurrence (pre-transplant HLA Class I antibodies p = 0.039p < 0.05; pre-transplant HLA Class II antibodies p = 0.011p < 0.05; post-transplant HLA Class I non-DSA antibodies p < 0.01; post-transplant HLA Class II non-DSA antibodies p < 0.01). In addition, HLA MM at locus A (hazard ratio (HR), 2.44; 95 % confidence interval (CI): 1.15-5.16; p = 0.01 hazard ratio (HR), 2.33; 95 % confidence interval (CI):1.132-4.805; p = 0.02) and DSA Class I (HR, 10.24; 95 % CI: 1.44-72.62; p = 0.02 HR, 5.539; 95 % CI: 1.264-24.272; p = 0.02) appeared to be significant predictors of poorer graft survival. Our investigation demonstrates the long medium-term experience of DSA development occurrence in patients with after kidney transplantation in Campania region - Italy.

Strozziero M ，Costa D ，Benincasa G ，Grimaldi V ，De Rosa P ，Valeriani G ，Santangelo M ，Carrano R ，Pacilio S ，Cacciatore F ，Napoli C ... -  《-》

Ethics of Procuring and Using Organs or Tissue from Infants and Newborns for Transplantation, Research, or Commercial Purposes: Protocol for a Bioethics Scoping Review.

Since the inception of transplantation, it has been crucial to ensure that organ or tissue donations are made with valid informed consent to avoid concerns about coercion or exploitation. This issue is particularly challenging when it comes to infants and younger children, insofar as they are unable to provide consent. Despite their vulnerability, infants' organs and tissues are considered valuable for biomedical purposes due to their size and unique properties. This raises questions about the conditions under which it is permissible to remove and use these body parts for transplantation, research, or commercial purposes. The aim of this protocol is to establish a foundation for a scoping review that will identify, clarify, and categorise the main ethical arguments regarding the permissibility of removing and using organs or tissues from infants. The scoping review will follow the methodology outlined by the Joanna Briggs Institute (JBI), consisting of five stages: (1) identifying the research question, (2) developing the search strategy, (3) setting inclusion criteria, (4) extracting data, and (5) presenting and analysing the results. We will include both published and unpublished materials that explicitly discuss the ethical arguments related to the procurement and use of infant organs or tissues in the biomedical context. The search will cover various databases, including the National Library of Medicine, Web of Science, EBSCO, and others, as well as grey literature sources. Two raters will independently assess the eligibility of articles, and data from eligible studies will be extracted using a standardised form. The extracted data will then be analysed descriptively through qualitative content analysis. There has been debate about how to respect the rights and interests of organ and tissue donors since the beginning of transplantation practice, given the moral risks involved in procuring parts of their bodies and using them for transplantation or research. A major concern has been to ensure that, at a minimum, donation of organs or other bodily tissues for transplantation or research is done under conditions of valid informed consent, so as to avoid coercion or exploitation among other moral harms. In the case of infants and younger children, however, this concern poses special difficulties insofar as infants and younger children are deemed incapable of providing valid consent. Due to their diminutive size and other distinctive properties, infants' organs and tissues are seen as valuable for biomedical purposes. Yet, the heightened vulnerability of infants raises questions about when and whether it is ever permissible to remove these body parts or use them in research or for other purposes. The aim of this protocol is to form the basis of a systematic scoping review to identify, clarify, and systematise the main ethical arguments for and against the permissibility of removing and using infant or newborn (hereafter, "infant") organs or tissues in the biomedical context (i.e. for transplantation, research, or commercial purposes). Our scoping review will broadly follow the well-established methodology outlined by the Joanna Briggs Institute ( Peters et al., 2020). We will follow a five-stage review process: (1) identification of the research question, (2) development of the search strategy, (3) inclusion criteria, (4) data extraction, and (5) presentation and analysis of the results. Published and unpublished bibliographic material (including reports, dissertations, book chapters, etc.) will be considered based on the following inclusion criteria: the presence of explicit (bio)ethical arguments or reasons (concept) for or against the procurement and use of organs or tissues from infants, defined as a child from birth until 1 year old (population), in the biomedical domain, including transplantation, research, and commercial development (context). We will search for relevant studies in the National Library of Medicine (including PubMed and MEDLINE), Virtual Health Library, Web of Science, Google Scholar, EBSCO, Google Scholar, PhilPapers, The Bioethics Literature Database (BELIT), EthxWeb as well as grey literature sources (e.g., Google, BASE, OpenGrey, and WorldCat) and the reference lists of key studies to identify studies suitable for inclusion. A three-stage search strategy will be used to determine the eligibility of articles, as recommended by the JBI methodological guidelines. We will exclude sources if (a) the full text is not accessible, (b) the main text is in a language other than English, or (c) the focus is exclusively on scientific, legal, or religious/theological arguments. All articles will be independently assessed for eligibility between two raters (MB & XL); data from eligible articles will be extracted and charted using a standardised data extraction form. The extracted data will be analysed descriptively using basic qualitative content analysis. Ethical review is not required as scoping reviews are a form of secondary data analysis that synthesise data from publicly available sources. Our dissemination strategy includes peer review publication, presentation at conferences, and outreach to relevant stakeholders. The results will be reported according to the PRISMA-ScR guidelines. An overview of the general data from the included studies will be presented in the form of graphs or tables showing the distribution of studies by year or period of publication, country of origin, and key ethical arguments. These results will be accompanied by a narrative summary describing how each included study or article relates to the aims of this review. Research gaps will be identified and limitations of the review will also be highlighted. A paper summarising the findings from this review will be published in a peer-reviewed journal. In addition, a synthesis of the key findings will be disseminated to biomedical settings (e.g., conferences or workshops, potentially including ones linked to university hospitals) in the UK, USA, Türkiye, and Singapore. They will also be shared with the academic community and policy makers involved in the organ procurement organisations (OPO), which will potentially consider our recommendations in their decision-making processes regarding infant tissue/organ donation practice in these countries. The use of a rigorous, well-established methodological framework will ensure the production of a high-quality scoping review that will contribute to the bioethics literature.A comprehensive search of disciplinary and cross-disciplinary databases will be undertaken to ensure coverage of all possible sources that meet the inclusion criteria for the review.This review will focus exclusively on infant tissue/organ procurement/use in biomedical contexts, providing a comprehensive and reliable source of ethical arguments for future debates on this sensitive topic.The review will be limited to articles published in English, which increases the risk of missing relevant sources published in other languages.The review will be limited to articles for which the full text is available, which increases the risk of missing relevant sources that otherwise may have been included in the scoping review had the full text been accessible.

Barış M ，Lim X ，T Almonte M ，Shaw D ，Brierley J ，Porsdam Mann S ，Nguyen T ，Menikoff J ，Wilkinson D ，Savulescu J ，Earp BD ... -  《-》