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The presence of anti-human leucocyte antigen (HLA) antibodies in the potential solid organ transplant recipient’s blood is one of the main barriers to access to a transplantation. The HLA sensitization is associated with longer waitlist time, antibody mediated rejection and transplant lost leading to increased recipient’s morbidity and mortality. However, solid organ transplantation across the HLA immunological barriers have been reported in recipients who were highly sensitized to HLA using desensitization protocols. These desensitization regimens are focused on the reduction of circulating HLA antibodies. Despite those strategies improve rates of transplantation, it remains several limitations including persistent high rejection rate and worse long-term outcomes when compare with non-sensitized recipient population. Currently, interest is growing in the development of new desensitization approaches which, beyond targeting antibodies, would be based on the modulation of alloimmune pathways. Plasma cells appears as an interesting target given their critical role in antibody production. In the last decade, CD38-targeting immunotherapies, such as daratumumab, have been recognized as a key component in the treatment of myeloma by inducing an important plasma cell depletion. This review focuses on an emerging concept based on targeting CD38 to desensitize in the field of transplantation.

Antibodies reactive to human leukocyte antigens (HLA) represent a barrier for patients awaiting transplantation. Based on reactivity patterns in single-antigen bead (SAB) assays, various epitope matching algorithms have been proposed to improve transplant outcomes. However, some antibody reactivities cannot be explained by amino acid motifs, leading to uncertainty about their clinical relevance. Antibodies against the HLA class II molecule, DQβ0603:DQα0103, present in some candidates, represent one such example. Here, we show that peptides derived from amino acids 119-148 of the HLA class I heavy chain are bound to DQβ0603:DQα0103 proteins and contribute to antibody reactivity through an HLA-DM-dependent process. Moreover, antibody reactivity is impacted by the specific amino acid sequence presented. In summary, we demonstrate that polymorphic HLA class I peptides, bound to HLA class II proteins, can directly or indirectly be part of the antibody binding epitope. Our findings have potential important implications for the field of transplant immunology and for our understanding of adaptive immunity. Bead-based assays to assess the donor-specific antibody profile of solid organ transplant patients often produce discordant results relative to cell-based alternatives. In this study, the authors demonstrate that, for some MHC class-II-specific antibodies, discordance can be attributed to recognition of the MHC class-I-derived peptides bound to MHC class-II molecules.

Background Managing infectious complications after kidney transplantation (KT) remains a major challenge. Infections are the leading non-cardiovascular cause of death among kidney transplant recipients (KTr). The urinary tract is particularly vulnerable to infections in this group, leading to high levels of morbidity and mortality, as well as significant economic costs. Case presentation This case report presents the first documented instance of extensive thigh pyomyositis resulting from cystic fistulae in an 84-year-old KTr. The patient was referred to our hospital with acute onset fever, pain in the inner thighs and pyuria. A CT scan revealed bilateral pyomyositis of the thighs, characterized by multiple abscesses in the adductor muscles and hydroaerobic levels. Additionally, cystic fistulae complicated by pubic symphysis osteitis were identified. Conclusion In KTr, lower limb pyomyositis resulting from a urinary tract infection is an extremely rare and significantly worsens the overall prognosis for these patients.

Due to its intrinsic complexity and the principle of collective solidarity that governs it, solid organ transplantation (SOT) seems to have been spared from the increase in litigation related to medical activity. Litigation relating to solid organ transplantation that took place in the 29 units of the Assistance Publique-Hôpitaux de Paris and was the subject of a judicial decision between 2015 and 2022 was studied. A total of 52 cases of SOT were recorded, all in adults, representing 1.1% of all cases and increasing from 0.71% to 1.5% over 7 years. The organs transplanted were 25 kidneys (48%), 19 livers (37%), 5 hearts (9%) and 3 lungs (6%). For kidney transplants, 11 complaints (44%) were related to living donor procedures and 6 to donors. The main causes of complaints were early post-operative complications in 31 cases (60%) and late complications in 13 cases (25%). The verdicts were in favour of the institution in 41 cases (79%). Solid organ transplants are increasingly the subject of litigation. Although the medical institution was not held liable in almost 80% of cases, this study makes a strong case for patients, living donors and their relatives to be better informed about SOT.

Background Patients with end‐stage renal disease may display both a loss of skeletal muscle mass and an increase in muscle fat deposits. We aimed to analyse the impact of low skeletal muscle mass index (SMI, surrogate marker of sarcopenia) and low muscle density (MD, surrogate marker of myosteatosis) on patient survival after kidney transplantation (KT). Methods In a retrospective cohort of 200 kidney transplant recipients (KTr), we measured on an unenhanced cross‐sectional computed tomography scan taken at the level of the third lumbar vertebra within the previous year or at the time of KT, both SMI (muscle cross‐sectional area normalized for height2, reported in cm2/m2) and MD (mean attenuation of muscle cross‐sectional area, expressed in Hounsfield units). We determined age‐specific and sex‐specific normality thresholds on 130 healthy subjects. The baseline factors associated with low MD were assessed by logistic regression analysis. Cox proportional hazard univariable and multivariable models were constructed to identify predictive factors of patient survival. Results Among the 200 patients of the cohort, 123 were male (62%), and mean age was 54.8 ± 13.8 years. A total of 181 KTr required renal replacement therapy before KT (91%), and 36 KTr (18%) received repeat kidney transplant after previous failed KT. Mean MD was 30.6 ± 9 HU in men and 29.7 ± 8.3 HU in women, whereas SMI was 49.7 ± 8.6 cm2/m2 in men and 42.3 ± 7.3 cm2/m2 in women. MD was below the 2.5th percentile for the healthy population in 49 KTr (25%), defining the myosteatosis group, while SMI was below the 2.5th percentile for the reference population in 10 KTr (5%). Independent risk factors for myosteatosis were two or more KT [adjusted odds ratio (aOR) 5.2, 95% confidence interval (95% CI): 2.22–12.4, P = 0.0001], a history of stroke (aOR 3.7, 95% CI: 1.30–10.7, P = 0.015), and body mass index > 25 kg/m2 (aOR 2.94, 95% CI: 1.4–6.18, P = 0.004). Myosteatosis was independently associated with mortality [adjusted hazard ratio (aHR) 2.12, 95% CI: 1.06–4.24, P = 0.033], as were cardiovascular disease (HR 2.06, 95% CI: 1.02–4.15, P = 0.043) and age (aHR 1.06, 95% CI: 1.03–1.09, P = 0.0003). Low SMI was not associated with mortality. Conclusions Myosteatosis, which was more prevalent than low skeletal muscle mass, might be an important prognostic marker in patients undergoing KT.

After kidney transplantation (KT), there is no reliable assessment of the immunosuppressive state. We analysed pre-KT T-, B- and NK-cell populations in relation to the occurrence of opportunistic infections (OI) or acute rejection (AR) after KT. We included 422 adult KT recipients from 01/2016 to 09/2020. Immune cells were analysed using flow cytometry in 283 recipients before KT in three groups: AR, OI or no event within 24 months after KT. There were 49 recipients in the OI group, 44 in the AR group and 190 in the control group. Before KT, higher absolute counts and percentages of NK cells (p=0.001 and p=0.007 respectively), elevated absolute counts of plasmablasts and CD21 CD38 B cells (age-associated B cells) (p=0.045 and p=0.028 respectively), and a lower proportion of CD3+ T cells (p=0.022) were independently associated with the occurrence of OI within two years following kidney transplantation (KT). In recipients with OI occurring before three months, only absolute count of NK cells before KT remained independently associated with the occurrence of OI (p=0.002). None of the studied immune cell population was associated with AR. Our results suggest that higher levels of pretransplant NK cells and age-associated B cells are correlated with the occurrence of OI within two years after KT. This result may improve stratification of individualized infectious risk prior to KT.

Fabry disease (OMIM #301 500), the most prevalent lysosomal storage disease, is caused by enzymatic defects in alpha-galactosidase A (GLA gene; Xq22.1). Fabry disease has historically been characterized by progressive renal failure, early stroke and hypertrophic cardiomyopathy, with a diminished life expectancy. A nonclassical phenotype has been described with an almost exclusive cardiac involvement. Specific therapies with enzyme substitution or chaperone molecules are now available depending on the mutation carried. Numerous clinical and fundamental studies have been conducted without stratifying patients by phenotype or severity, despite different prognoses and possible different pathophysiologies. We aimed to identify a simple and clinically relevant way to classify and stratify patients according to their disease severity. Based on data from the French Fabry Biobank and Registry (FFABRY; n = 104; 54 males), we applied unsupervised multivariate statistics to determine clusters of patients and identify clinical criteria that would allow an effective classification of adult patients. Thanks to these criteria and empirical clinical considerations we secondly elaborate a new score that allow the severity stratification of patients. We observed that the absence of acroparesthesia or cornea verticillata is sufficient to classify males as having the nonclassical phenotype. We did not identify criteria that significantly cluster female patients. The classical phenotype was associated with a higher risk of severe renal (HR = 35.1; p <10-3) and cardiac events (HR = 4.8; p = 0.008) and a trend toward a higher risk of severe neurological events (HR = 7.7; p = 0.08) compared to nonclassical males. Our simple, rapid and clinically-relevant FFABRY score gave concordant results with the validated MSSI. Acroparesthesia and cornea verticillata are simple clinical criteria that efficiently stratify Fabry patients, defining 3 different groups: females and males with nonclassical and classical phenotypes of significantly different severity. The FFABRY score allows severity stratification of Fabry patients.

Background Computed tomography (CT) scan–defined myosteatosis is a common feature in ESKD patients receiving kidney transplantation (KT) and is associated with mortality after KT. We aimed to explore the impact of myosteatosis and other CT scan based morphometric data on the occurrence of early surgical complications after KT. Methods We retrospectively measured on an unenhanced cross‐sectional CT scan taken at the middle of the third lumbar vertebra performed within the previous year or at the time of KT: surface muscle index (total lumbar cross‐sectional muscle area [CSMA] divided by height squared), subcutaneaous adipose tissue index, visceral adipose tissue index and muscle density (MD: mean CT attenuation of CSMA). Vessel to skin distance was the distance between iliac vein and skin. Myosteatosis was defined as MD below age‐ and sex‐specific normal values. Logistic regression models were constructed to identify predictive factor of 90 days postoperative surgical complications with Clavien–Dindo score greater than or equal to 2, CD ≥ 2). Results Among the N = 200 patients, 61.5% were male with a mean age of 54.8 (± 13.8) years and a mean BMI of 25.1 (± 4.4) kg/m2. Sixty patients (30%) developed at least one postoperative complication (CD ≥ 2) in the first 3 months after KT. In two different multivariate analyses, MD (aOR: 0.95 for one Hounsfield unit increase, 95% CI: 0.91–0.99, p = 0.028) and myosteatosis status (aOR: 4.64, 95% CI: 2.18–9.90, p < 0.0001) were the only independent risk factors for postsurgical complication. Conclusions Myosteatosis is independently associated with the occurrence of CD ≥ 2 postoperative complication within 90 days of surgery.

In sensitized deceased donor kidney allograft recipients, the most frequent induction therapy is anti-thymocyte globulins (ATG), including Thymoglobulin® (Thymo) and ATG-Fresenius (ATG-F). We conducted a 3-year monocentric observational study to compare the impact of ATGs on hematological parameters. We included adult kidney transplant recipients treated with ATG induction therapy, either Thymo or ATG-F, on a one-in-two basis. The primary endpoint was red blood cell (RBC) transfusions within 14 days after transplantation. Among 309 kidney allograft recipients, 177 (57.2%) received ATG induction, 90 (50.8 %) ATG-F, and 87 (49.2%) Thymo. The ATG-F group received significantly more RBC transfusions (63.3% vs. 46% p = 0.02) and in bigger volumes (p = 0.01). Platelet transfusion was similar in both groups. Within 14 and 30 days after transplantation, older age, ATG-F induction, and early surgical complication were independently associated with RBC transfusion. Patient survival rate was 95%, and the death-censored kidney allograft survival rate was 91.5% at 12 months post-transplantation. There was no difference in the incidence of acute rejection and infections or in the prevalence of anti-HLA donor-specific antibodies. In conclusion, after kidney transplantation, ATG-F is an independent risk factor for early RBC transfusion and early thrombocytopenia without clinical and biological consequences. These new data should be clinically considered, and alternatives to ATG should be further explored.