While lymphodepletion is considered a therapeutic effect of rabbit anti-thymocyte globulin (rATG), a concomitant decrease in basophil count (BC) has unknown clinical effect.

Autologous stem cell transplantation (ASCT) imposes significant immunogenic effects that may also underlie some of its anti-tumor effectiveness. Despite improvements in disease risk stratification and treatment approaches with high cure and response rate for newly diagnosed Hodgkin lymphoma (HL) with initial therapy in most patients, a significant proportion will be experiencing refractory or relapsed (R/R) following the initial front-line therapy. A high-dose chemotherapy followed by ASCT remains the standard treatment for relapsed Hodgkin disease in adult patients. The aim of our study was to identify the impact of ASCT on outcomes in R/R HL, considering various pre- and post-ASCT parameters as prognostic predictors, including disease status response, time of absolute neutrophils, and lymphocyte recovery counts post ASCT.

Ex-vivo depletion of donor CD45RA+ naïve T-cells can reduce graft-versus-host-disease (GVHD) in haploidentical hematopoietic stem cell transplantation (HSCT) while providing memory T-cells to reduce infections. CD62L is another marker of naïve T-cells. Depletion of CD62L+ cells may offer advantages of removing central memory T-cells which may also cause mild GVHD, and retain CD45RA+ effector memory T-cells (TEMRA). We aimed to evaluate the depletion efficiency, safety and immunoreconstitution after novel CD62L depleted donor lymphocyte infusion (DLI) with T-cell receptor (TCR)-αβ depleted haploidentical HSCT. Children with malignant or non-malignant diseases who underwent the first TCRαβ depleted haploidentical HSCT were recruited to receive CD62L depleted DLI on day 0 at a dose of 1 × 10/kg or 5 × 10/kg CD3 + CD62L- cells using the CliniMACS device. Six children aged 0.3-15 years received 4.6-10 × 10/kg CD34+ cells. CD62L depletion resulted in undetectable CD3 + CD62L+ cells in 4 patients and 3.39-3.52 log reduction in 2 patients. Infusion was well-tolerated. All patients had neutrophil and platelet engrafted early (medians 10 and 9.5 days respectively) with 100 % donor chimerism. Only one patient had grade 1 acute GVHD. None had chronic GVHD. Post-transplant recovery of CD3+ cells reached a median of 117/uL at 1 month and as high as 352/uL at 3 months. TEMRA cells were present at 1 month (median 2 cells/uL) and increased 3 months post-transplant (median 21 cells/uL). In conclusion, CD62L depletion is highly efficient and appears safe and does not affect engraftment. It provides TEMRA and effector memory T-cells to protect the recipient against infections. Risk of GVHD is low.

Sepsis-induced acute kidney injury (AKI) is a severe condition characterized by dysregulation of pro- and anti-inflammatory responses. Targeting macrophage polarization between pro-inflammatory M1 and anti-inflammatory M2 cells offers a potential therapeutic approach for AKI. Trametinib (TRAM), an inhibitor of the MEK1/2 signaling pathway, was evaluated for its impact on M1/M2 polarization in AKI.

Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Studies have shown that mitochondrial damage is involved in the pathogenesis of AKI, and that inhibition of Hsp90 expression can improve IR-induced AKI. However, the mechanisms by which Hsp90 improves IR-induced AKI and whether it is involved in mitochondrial autophagy remain unclear.

Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a rare but severe complication following solid organ transplantation (SOT). Currently, treatment regimens still lack clear guidelines.

The huge diversity of Human Leukocyte Antigen (HLA) system is well-known to be associated with various diseases, anthropology, population genetics, and transplantation. The frequencies of HLA alleles in different populations are crucial for both research and clinical applications. This study determined the allelic and haplotype frequencies of all HLA class I and class II loci in 595 consecutive samples from patients who underwent solid organ transplantation (SOT) and hematopoietic progenitor cell transplantation (HPCT).

For CMV high-risk constellations, guidelines recommend 3-6 months of prophylaxis with valganciclovir (VGCV). Management in preventing CMV primary infection in patients developing VGCV-associated leukopenia remains challenging.

Tacrolimus is a backbone for immunosuppression after allogeneic stem cell transplantation (AlloSCT). There is no sufficient kinetic data demonstrating the consistency of maintaining therapeutic levels. Herein, we measured the kinetic of therapeutic range (TTR) and its impact on outcomes of AlloSCT. Our local observational cohort included 186 adult AlloSCT performed at Hospital Austral between January 2012 and December 2019. An additional external cohort included 307 adult patients with AlloSCT from the University of Utah. We defined adequate TTR as >75 % of the measurements between 5.0 and 15.0 ng/mL during the first 30 days post-transplantation. In our local cohort, 55 % of patients had adequate TTR values. Primary graft failure was significantly lower in patients with adequate TTR (2 %, 95 % CI 0.5-7.7 % vs. 10 %, 95 % CI 5-18 %, p = 0.01). Non relapse mortality (NRM) was significantly lower with adequate TTR (17 %, 95 % CI 11-26 % vs. 33 %, 95 % CI 24-43 %; p < 0.01). Similarly, the external cohort had an NRM value significantly reduced in patients with adequate TTR values. In the pooled data analysis of local and external groups (n = 493), the TTR value below minimal range (≥25 % of measurements <5 ng/mL) was an independent risk factor for graft failure, as well as for NRM rate (44 %, 95 % CI 30-57 % vs. 18 %, 95 % CI 15-22 %) (p < 0.001) and lower OS at 3 years (47 %, 95 % CI 26-55 % vs. 56 %, 95 % CI 49-59 %, p < 0.001). These findings showed the importance of adequate TTRs during the first month after AlloSCTs. Sub-therapeutic TTR values were associated with worse survival outcomes.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder primarily distinguished by synovial inflammation, which, as the disease evolves, can lead to bone erosion and destruction. Consequently, the pivotal strategy in preventing joint damage and fostering functional recovery lies in the effective management of synovial inflammation. Disease-modifying antirheumatic drugs (DMARDs) and prednisone therapy remain the first-line treatments for RA. However, in instances of refractory RA, these medications may fall short in adequately controlling inflammation, and they are often accompanied by several adverse effects, including limited bioavailability, therapeutic resistance, and potentially toxic side effects. Given these challenges, the identification of targeted therapies to manage disease activity and diminish inflammation becomes imperative.Recently, biologic agents for the treatment of RA have garnered significant attention owing to their minimal side effect profile, reduced potential for drug dependence, and their precise therapeutic action directly on target cells. This review provides a comprehensive exploration of advancements in biologics that target and inhibit inflammatory cytokine receptors, specifically TNF-α, IL-6, and IL-1β, as well as B lymphocyte receptors, TLR4, nanodrugs, and Janus kinase (JAK) inhibitors in the context of RA. By providing innovative perspectives and strategies for the treatment of this condition, this review contributes to the ongoing efforts to refine and improve the therapeutic landscape for RA.

Antibody-mediated rejection (AMR) has been recognized as a significant cause of acute and chronic lung allograft dysfunction after lung transplantation. Some treatments, eculizumab, an anti-complement (C)5 component monoclonal antibody (Mab), seem to have a promising effect in the management of some patients with AMR. We present two patients with acute AMR after lung transplantation who received the anti-C5 Mab therapy. In both cases, we identified the presence of C4d deposition in the peritubular capillaries on trans-alveolar biopsies, which suggested activation of complement in AMR. Prior to eculizumab therapy, both patients had also received immunoadsorption, courses of intravenous immunoglobulins (IVIG) and rituximab. For the first patient, we have shown that eculizumab can serve as an effective bridge to re-transplantation. For the second patient, we observed the absence of clinical and biological efficacy, and without a clear therapeutic efficacy the therapy with eculizumab had been discontinued after two months.

Characteristic alterations in the urinary microbiome, or urobiome, are associated with renal transplant pathology. To date, there has been no direct study of the urobiome during acute allograft rejection. The goal of this study was to determine if unique urobiome alterations are present during acute rejection in renal transplant recipients. We performed shotgun metagenomic sequencing of 32 mid-stream urine samples obtained from 15 transplant recipients pre-transplant, 1- and 3-months post-transplant, and at time of rejection discovered with for-cause biopsy. Within individuals, there was a 40-60 % difference in urobiome composition from pre-to-post-transplant in both rejectors and non-rejectors. The taxa Ureaplasma was enriched in rejectors compared to non-rejectors. However, a greater number of microbial genes were enriched in non-rejectors compared to rejectors, except for genes associated with tetracycline resistance, the lysophosphatidic acid synthesis pathway, and tryptophanyl-tRNA synthetase. Together, our findings suggest that the urobiome is significantly altered post-transplant with certain taxa and/or microbial genes potentially associated with acute allograft rejection/inflammation.

The cuproptosis is an intracellular copper (Cu) accumulation triggering the aggregation of mitochondrial lipoylated proteins and destabilization of iron‑sulfur (FeS) cluster proteins, leading to cell death. This copper-triggered modality of mitochondrial cell death has been associated with cuproptosis-related signature key genes (CRGs). Our study focused on the relationship between the cuproptosis CRGs and diabetic nephropathy (DN) to understand how such immune microenvironment may influence DN.

The rate of immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays the principal role in the development of serious post-transplant complications. However, the post-transplantation course has a significant impact on shaping the immune system of the recipient, per se, thus representing risk factors for subsequent unfavorable outcomes. The predictive power of an interferon gamma (IFNγ) release assay (IGRA) on graft-versus-host disease (GVHD) or hematological relapse in recipients of allo-HSCT treated with post-transplantation cyclophosphamide and the impact of these complications on the restoration of cellular immune responsiveness was evaluated.

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.

This retrospective study analyses the impact HLA heterozygosity, supertypes, and alleles have on incidence of graft versus host disease (GvHD), relapse, overall survival (OS), disease-free survival (DFS) and transplant-related mortality (TRM) after HSCT. The study included patients who underwent HSCT, typed at allele resolution level for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci. The analysis performed on the entire patient cohort (N = 232) showed that HLA-B07 supertype positive patients demonstrated decreased incidence of relapse, better OS and DFS in comparison to those negative for HLA-B07 supertype. Further, a higher incidence of TRM was observed among patients positive for HLA-B27 supertype. Significant association of the HLA-A*02:01 allele presence with decreased incidence of GvHD was found. The occurrence of HLA-A*11:01 allele was associated with a worse OS, DFS and a higher rate of TRM. The analysis of the subgroup of patients with AML or MDS (N = 148) showed an association of HLA-A24 supertype with a worse OS. The HLA-B07 supertype positive patients demonstrated a lower incidence of relapse and a better DFS. A decline in OS and a higher TRM rate were observed among patients positive for HLA-B27 supertype. The presence of HLA-A*11:01 allele was indicative of a worse OS, DFS and a higher rate of TRM. The associations of HLA and HSCT clinical outcome parameters found in this study justify further investigation of this matter.

Circular RNAs (circRNAs) act as vital players in multiple myeloma (MM). Herein, we focused on the function of hsa_circ_0003489 (circ_0003489) in MM development and bortezomib (BTZ) resistance.

Cytomegalovirus (CMV) is a virus of the herpesviridae family. CMV infection is associated with increased morbidity and mortality in immunocompromised subjects such as hemodialysis patients and transplant recipients. The aim of our study was to determine the serological status of potential kidney recipients and donors in order to assess the risk of post-transplant CMV infection and disease.

Hemophagocytic lymphohistiocytosis (HLH) is a severe disorder with poor clinical outcomes. Use of emapalumab, an IFN-γ inhibitor, enables primary HLH control in over 85 % of affected children. However, data on emapalumab use for Epstein-Barr virus-associated HLH (EBV-HLH) are limited. This report presents the cases of three patients with EBV-HLH, highlighting the successful integration of low-dose emapalumab in combination with chemotherapy as a novel therapeutic approach for patients diagnosed with EBV-HLH. This regimen resulted in rapid disease symptom control and hematological parameter improvement and facilitated successful stem cell transplantation. This report highlights the potential of low-dose emapalumab combined with chemotherapy as an effective bridging therapy to allogenic hematopoietic stem cell transplantation in EBV-HLH patients.

Tacrolimus-induced thrombotic microangiopathy (TMA) causing acute kidney injury (AKI) without systemic features is a rare entity, particularly after non-renal solid organ transplantation.

Cytomegalovirus (CMV) is a common clinical infection especially after organ transplantation and threaten the survival of recipients. Natural killer (NK) cells play an important role in the process of CMV infection. In this study, we want to explore that if the different of killer immunoglobulin-like receptors (KIRs) of NK cells could affect CMV infection.