The new HLA-DRB3*03:69 allele differs from DRB3*03:01:01:03 by change of C → G in exon 3.

Gamma delta (γδ) T cells represent a minor fraction of human T cell repertoire but play an important role in mediating anti-infectious and anti-tumorous effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a prospective study to analyze the effect of different transplant modalities on immune reconstitution of γδ T cells and subsets. CD3, CD4 and CD8 T cells were analyzed in parallel. Secondly, we examined the impact of γδ T cell reconstitution on clinical outcomes including acute Graft-versus-Host-Disease (aGvHD) and viral infections. Our cohort includes 49 pediatric patients who received unmanipulated bone marrow grafts from matched unrelated (MUD) or matched related (MRD) donors. The cohort includes patients with malignant as well as non-malignant diseases. Cell counts were measured using flow cytometry at 15, 30, 60, 100, 180 and 240 days after transplantation. Cells were stained for CD3, CD4, CD8, CD45, TCRαβ, TCRγδ, TCRVδ1, TCRVδ2, HLA-DR and combinations. Patients with a MRD showed significantly higher Vδ2+ T cells than those with MUD at timepoints +30, +60, +100 (p<0.001, respectively) and +180 (p<0.01) in univariate analysis. These results remained significant in multivariate analysis. Patients recovering with a high relative abundance of total γδ T cells and Vδ2+ T cells had a significantly lower cumulative incidence of grade II-IV aGvHD after transplantation (p=0.03 and p=0.04, respectively). A high relative abundance of Vδ2+ T cells was also associated with a lower incidence of EBV infection (p=0.02). Patients with EBV infection on the other hand showed higher absolute Vδ1+ T cell counts at days +100 and +180 after transplantation (p=0.046 and 0.038, respectively) than those without EBV infection. This result remained significant in a multivariate time-averaged analysis (q<0.1). Our results suggest a protective role of γδ T cells and especially Vδ2+ T cell subset against the development of aGvHD and EBV infection after pediatric HSCT. Vδ1+ T cells might be involved in the immune response after EBV infection. Our results encourage further research on γδ T cells as prognostic markers after HSCT and as possible targets of adoptive T cell transfer strategies.

HLA-DQB1*02:211 allele differs from DQB1*02:02:01:02 by change of C → A in exon 2.

UNASSIGNED: Bone marrow transplantation (BMT) saves lives in Omenn syndrome, a severe immunodeficiency disorder. Timely genetic diagnosis and matched donor BMT are crucial. Emphasis on newborn screening and multidisciplinary care improves outcomes for infants with inherited disorders. Prompt intervention and comprehensive management are vital for a successful transplant outcome.
UNASSIGNED: Omenn syndrome represents a severe variant of combined immunodeficiency characterized by disregulated immune responses and susceptibility to recurrent infections. We present the case of a 3-month-old female infant initially presenting with upper respiratory infection symptoms and a diffuse rash, unresponsive to local treatment. At 4 months of age, the patient underwent allogeneic bone marrow transplantation (BMT) utilizing stem cells from a fully matched sibling donor. Pre-transplant conditioning included antimicrobial prophylaxis and supportive therapies. Following BMT, the patient received immunosuppressive medications to prevent graft rejection and graft-versus-host disease. Clinical monitoring post-transplant showed timely neutrophil and platelet engraftment, with subsequent follow-up demonstrating stable clinical parameters and negative cytomegalovirus status. The case highlights the importance of timely diagnosis and treatment in managing severe immunodeficiency disorders, demonstrating the potential for successful outcomes with appropriate timely interventions. Regular monitoring and follow-up appointments were crucial in ensuring the success of the treatment. This case also emphasizes the significance of multidisciplinary care and genetic testing in identifying and managing rare immunodeficiency disorders. The successful outcome in this case provides hope for improved treatment options and better patient outcomes in the future.

Aim: To assess the efficacy of a bioregenerative scaffold derived from bone marrow aspirate, cancellous bone autograft, platelet-rich plasma and autologous fibrin in treating supracondylar femur nonunions. Methods & materials: Three patients with nonunions following multiple surgical failures underwent bone stabilization and the application of a novel bioregenerative scaffold. x-rays and subjective scales were collected before surgery and at 6, 12 and 24 months post-surgery. Results: All nonunions exhibited healing with sufficient callus formation, as confirmed radiologically. After 6 months, all patients resumed full weight-bearing walking without pain. Statistical analysis showed improvements in all scales compared with pre-surgical values. Conclusion: This method presents itself as an option for treating supracondylar femur nonunions following multiple surgical failures.
What is this summary about? The objective of this case series study was to evaluate the effectiveness of a new biological autologous scaffold, comprised of stem and blood cells along with blood derivatives, in treating challenging cases of supracondylar femur nonunions.What were the results? Three participants underwent the application of this surgical method and were monitored for a period of 2 years. The therapy was well tolerated and deemed safe. Notably, all three patients experienced significant reductions in pain and improvements in functionality. Within a few months, they were able to walk with full weightbearing without pain, and clear indications of progressing toward bone union were evident by the 6 months.What do the results mean? This study demonstrates that the surgical application of autologous blood, cancellous bone and bone marrow, following the described concept and method, is an effective, safe and enduring treatment for femur nonunions. It markedly diminishes pain, enhances leg function and yields statistically significant improvements in quality of life.

The development of autoimmune diseases (ADs) is thought to be caused by a dysfunction of the intrinsic ability of our immune system for \"self-nonself\" discrimination. Following the breakdown of \"self-tolerance,\" an orchestrated immune cascade develops, involving B- and T-lymphocytes and autoantibodies that target self-antigens. An imbalance of the regulatory immune network and a suitable genetic background, along with external (infectious and environmental) triggers, are all important contributors to the outbreak of clinical autoimmunity. Immunotherapies for ADs can be classified into treatments that are given continuously (chronic treatments) and therapies that are applied only once or intermittently, aiming to induce partial or complete reconstitution of the immune system [immune reconstitution therapies (IRTs)]. The principle underlying IRTs is based on the depletion of mature immune cells and the rebuilding of the immune system. During this process of immune reconstitution, a substantial change in the lymphocyte repertoire occurs, which may explain the impressive and long-term beneficial effects of IRTs, including the possibility of induction of tolerance to self-antigens. Hematopoietic (or bone marrow) stem cell transplantation (HSCT or BMT) represents the prototype-and the most radical type-of IRT therapy. The rationale for HSCT or BMT for the treatment of severe ADs is based on convincing proof in preclinical studies, utilizing various animal models of autoimmunity. More than 30 years\' worth of pioneering experiments in various models of ADs have shown that HSCT can lead to substantial improvement or even cure of the autoimmune syndromes and induction of long-term tolerance to autoantigens. The success of treatment depends on how completely the autoantigen-reactive lymphocytes and memory cells are eradicated by the conditioning chemotherapy, which is administered in a single dose before the transplantation. The most successful conditioning methods in animal models of ADs are total body irradiation (TBI) and high-dose cyclophosphamide (CY). These preclinical studies, summarized in this review, have provided important data about the therapeutic potential of HSCT in human ADs and the associated mechanisms of action and have contributed to the formulation of guidelines for clinical applications of autologous or allogeneic HSCT/BMT in refractory autoimmunity.

BACKGROUND: In this study the tibial shaft fracture non unions in diabetes mellitus are evaluated with percutaneous autologous platelet gel supplementation to accelerate union are compared with individually matched control group with autologous iliac crest bone marrow aspirate injection.
METHODS: This present study was carried out on tibial non unions in diabetic patients recruited in an ongoing longitudinal study over a period of 2006 to 2017, treated by one surgeon at one institute, are included in this report. Each of 18 established tibial atrophic, aseptic non unions treated by percutaneous autologous platelets and iliac crest bone marrow aspirate were followed up on regular basis up till 9 months. The healing of non union was assessed clinically by painless full weight bearing and the radiological union was judged by bridging callus formation observed on at least 3 of 4 cortices in anteroposterior and lateral views.
RESULTS: Union was observed in 17 (94.4 %) patients of the autologous platelet group. The average time to union was 9.2 weeks (range 8 to 18 weeks) after percutaneous autologous platelet injection (P < 0.0517) .In the control group, union was observed in 14 (77.8 %) patients (P = 0.672). The average time to union following percutaneous bone marrow injection was 11.6 weeks (range 9 to 28 weeks). The proximal 1/3 shaft non union healed comparatively faster than the distal 1/3 shaft tibia (P ≤ 0.0612). No correlation was observed between the comminuted and non comminuted fracture non union (P = 0.789). A significant correlation was noted as regards the non union healing time duration in patients who were on insulin and oral hypoglycemic drugs (P ≤ 0.001) and also about the total duration of diabetes mellitus in years (P ≤ 0.003).
CONCLUSIONS: This investigation showed that percutaneous autologous platelet gel delivery is sufficient method to obtain union in diabetic tibial fracture non unions, which is less invasive procedure than bone marrow injection. The efficacy of this autologous platelets is once again well established and this study reinforced categorically the previously published report by the author.

UNASSIGNED: Invasive fungal diseases (IFD) constitute a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) recipients.
UNASSIGNED: We describe epidemiology, causes and risk factors of IFD in allogeneic HSCT discussing prophylaxis and treatment in various HSCT phases. We present the most recent studies on this thematic area, including novel data on currently available antifungals, i.e. formulations, dosing, safety, efficacy and therapeutic drug monitoring. Finally, we present the most recent relevant recommendations published. Literature search included PubMed, Scopus, and clinicaltrials.gov between January 2014 and April 2024.
UNASSIGNED: The antifungal agents employed for prophylaxis and therapy should be predicated on local epidemiology of IFD. Fluconazole prophylaxis remains a first-line choice before engraftment when the main pathogen is Candida spp. After engraftment, prophylaxis should be with mold-active agents (i.e. triazoles). For candidiasis, echinocandins are suggested as first-line treatment, whereas aspergillosis responds well to mold-active azoles and liposomal amphotericin B (L-AmB). For mucormycosis, treatment of choice includes L-AmB and isavuconazole. Choice between fever-driven and diagnostics-driven strategies remains equivocal. Open research topics remain: 1) optimization of tools to ensure prompt and accurate IFD diagnosis to avoid unnecessary exposure to antifungals, drug interactions and cost; 2) refinement of treatment for resistant/refractory strains.

The novel HLA-DPB1*14:01:15 allele differs from DPB1*14:01:01:01 by change of C > T in exon 3.

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