Transplant immunology最新文献

Background

Glycosylation is a complex and fundamental metabolic biosynthetic process orchestrated by multiple glycosyltransferases (GT) and glycosidases enzymes. Functions of GT have been extensively examined in multiple human diseases. Our study investigated the potential role of GT genes in T-cell mediated rejection (TCMR) and possible prediction of graft loss of kidney transplantation.

Methods

We downloaded the microarray datasets and GT genes from the GEO and the HUGO Gene Nomenclature Committee (HGNC) databases, respectively. Differentially expressed GT genes (DE-GTGs) were obtained by differential expression and Venn analysis. A TCMR diagnostic model was developed based on the hub DE-GTGs using LASSO regression and XGboost machine learning algorithms. In addition, a predictive model for graft survival was constructed by univariate Cox and LASSO Cox regression analysis.

Results

We have obtained 15 DE-GTGs. Both GO and KEGG analyses showed that the DE-GTGs were mainly involved in the glycoprotein biosynthetic process. The TCMR diagnostic model exhibited high diagnostic potential with generally highly correlated accuracies [aera under the curve (AUC) of 0.83]. The immune characteristics analysis revealed that higher levels of immune cell infiltration and immune responses were observed in the high-risk group than in the low-risk group. In particular, the Kaplan-Meier survival analysis revealed that renal grafts in the high-risk group have poor prognostic outcomes than the low-risk group. The predictive AUC values of 1-, 2- and 3-year graft survival were 0.76, 0.81, and 0.70, respectively.

Conclusion

Our results indicated that GT genes could be used for diagnosis of TCMR and prediction of graft loss in kidney transplantation. These results provide new perspectives and tools for diagnosing, treating and predicting kidney transplant-related diseases.

One of the issues during the post-transplant phase is anemia. The increased risk of graft rejection makes evaluating transplant recipients difficult. Parvovirus-B19 (PV-B19) should be considered one of the differential diagnosis of post-transplant anemia (PTA) in renal transplantation recipients. In this article, we report a 32 year old man who was admitted to the hospital with anemia. During the assessment, infection with PV-B19 was confirmed as the cause of the anemia. He received intravenous immunoglobin (IVIG) as the treatment.

Introduction

The scarcity of suitable donor organs has led to the inclusion of Expanded Criteria Donor (ECD) kidneys to augment the donor pool, despite potential concerns regarding post-transplant outcomes.

Methods

This retrospective study analyzed the clinical outcomes of a cohort of 317 kidney transplant recipients from deceased donors at a single center between 2008 and 2018. Patients were categorized into ECD and Standard Criteria Donor (SCD) groups, with primary nonfunctioning grafts excluded. Comprehensive laboratory evaluations were conducted, including HLA typing and serum creatinine levels. Immunosuppressive regimens were standardized, and statistical analyses were performed using the SPSS program.

Results

The sample consisted of 83 (26.18%) patients who received kidney transplants from ECDs and 234 (73.82%) from SCDs. The ECD group showed a longer cold ischemia time (p = 0.019) and a higher rate of delayed graft function (DGF) compared with the SCD group. No significant differences were observed in graft survival (p = 0.370) or patient survival (p = 0.993) between the ECD and SCD groups. However, differences in graft survival were noted between the groups when stratified by DGF status: ECD with DGF vs. ECD without DGF (p = 0.029), ECD with DGF vs. SCD with DGF (p = 0.188), ECD with DGF vs. SCD without DGF (p = 0.022), ECD without DGF vs. SCD with DGF (p = 0.014), ECD without DGF vs. SCD without DGF (p = 0.340), and SCD with DGF vs. SCD without DGF (p = 0.195). No differences in patient survival rates were observed among these groups for all pairwise comparisons (p > 0.05) when stratified by donor criteria and DGF status.

Conclusions

Graft and patient survival rates were comparable between ECD and SCD kidney transplant recipients.

Background

Severe combined immunodeficiency (SCID) is a heterogenous disorder with profound deficiency of T/B-cell functions. The best SCID therapy requires hematopoietic stem cell transplantation (HSCT) early in life. HSCT with conditioning is necessary to achieve a long-term reconstitution of B-cell functions. However, conditioning may aggravate pre-existing infection and cause transplant-related toxicity, especially in very young infants. Hence, the intensity of conditioning should be reduced to allow the reconstitution of immunity including B cells to the extent that prevents transplant-related toxicity and delayed complications.

Methods

An infant with a family history of X-linked SCID (X-SCID) was diagnosed with X-SCID disorder soon after birth. The infant exhibited cytomegalovirus (CMV) infection despite being strictly isolated. At 1.5 months of age, we performed an unrelated cord blood transplantation (CBT) with a less intensity conditioning regimen: fludarabine (125 mg/m²) + melphalan (80 mg/m²). We evaluated the efficacy of reconstitution by assessing B-cell function and growth and psychomotor development at 5 years and 7 months after CBT.

Results

The clinical course after CBT was uneventful after CBT. The CMV infection was fully controlled by ganciclovir or foscavir therapy, which was discontinued at day 55 after CBT. Furthermore, immunoglobulin (Ig) replacement therapy was also discontinued at 6 months after CBT. A sufficient proportion of CD27⁺ memory B cells was developed, which was essential for an effective vaccination and prevention of infections. While the B-cell chimerism became recipient-dominant, the Ig replacement therapy was substituted by very successful post-vaccine immunity acquisition after CBT. The analysis of the general developmental parameters showed that chemotherapy did not cause any delay in growth and psychomotor development.

Conclusions

The CBT therapy with this conditioning regimen was well tolerated and induced an effective reconstitution of B-cell functions in an X-SCID infant under the 3 months of age.

Donor-transmitted malignancy is a rare and often fatal complication of organ transplantation. We report a case of a 55-year old male kidney transplant recipient who was diagnosed with stage-IV donor-transmitted melanoma 5 months after transplantation with metastases in the liver, spleen, lung, and brain. Immunosuppression was discontinued, and encorafenib and binimetinib, inhibitors of a serine/threonine B-Raf proto-oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) respectively, were started. Severe rejection ensued and necessitated the start of hemodialysis as well as urgent graft nephrectomy. However, the tumor progressed and BRAF/MEK inhibition was replaced by immune-checkpoint inhibition with ipilimumab and nivolumab. When this also failed to slow disease progression and seizures occurred, therapy with encorafenib and binimetinib was reinstated. Afterwards, most of the metastases remained stable. The patient has now survived for more than 4 years in good general health, which is an exceptionally long survival with donor-transmitted, metastasized melanoma.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly invasive hematological malignancy originated from T-lineage progenitor cells. The clonal proliferation and aggregation of primordial cells in bone marrow inhibit normal hematopoietic function, resulting in a series of hematocytopenia and infiltration symptoms. SET-NUP214 fusion is a recurrent event that is common in adult male T-ALL patients. It originates from chromosome del(9)(q34.11; q34.13) or t(9; 9)(q34; q34). Hematopoietic stem cell transplantation (HSCT) can significantly improve the survival rate of these patients. Due to the poor prognosis of patients and high relapse rate after remission, more effective strategies need to be proposed to improve prognosis and prevent relapse. Chidamide is a novel oral benzamide histone deacetylase inhibitor (HDACi) that can exert anti-tumor effects through multiple mechanisms. Here we report chidamide maintenance therapy after allo-HSCT in patients with SET-NUP214 fusion positive T-ALL. Both patients improved effectively during follow-up, confirming the efficacy of chidamide in improving the condition of these patients and may provide valuable clinical information for the treatment of this rare and understudied disease.

Introduction

A better understanding of the immune mechanisms involved in allograft rejection after transplantation is urgently needed to improve patient outcomes. As microRNA-155 (miR155) plays a critical role in inflammation, we postulated that a deficiency of miR155 will improve cardiac allograft survival and enhance tolerance induction after heart transplantation.

Methods

We developed an acute rejection mouse model through heterotopic BALB/c cardiac transplantation to C57BL/6 (wild-type) and C57BL/6 miR155 knock-out (miR155KO) mice. Further, we induced tolerance in both groups through a costimulatory blockade with CTLA4-Ig (200 μg; post-transplant day 2) and MRI antibodies (250 μg; post-transplant day 0), targeting CD28/B7 and CD40/CD154 signals, respectively. Finally, we examined the effects of injecting 100 μg of small extracellular vesicles (sEVs) isolated from wild-type mice undergoing rejection into tolerant miR155KO mice.

Results

Mean survival time (MST) of the cardiac allografts in wild-type and miR155KO mice was 7 and 15 days, respectively (p < 0.0001). Costimulatory blockade increased MST to 65 days and > 100 days in the wild-type and miR155KO recipients, respectively (p < 0.001). Injection of sEVs isolated from wild-type mice undergoing rejection into tolerant miR155KO mice decreased the allograft survival to 9 days, significantly lower than the tolerant miR155KO mice without injection of sEVs (>100 days; p < 0.0001).

Conclusion

miR155KO mice have improved cardiac allograft survival and enhanced induction of tolerance after heterotopic cardiac transplantation. Injection of sEVs from wild-type mice undergoing rejection into the miR155KO mice reversed these benefits.

Background

The potential of Tocilizumab (TCZ) in preventing the cytokine storm caused by COVID-19 infection has been observed, while the survival benefits were inconclusive in solid-organ transplant recipients. We aimed to explore whether the timing of TCZ administration holds significance in the clinical course of COVID-19 infection and identify predicative factors of TCZ efficacy.

Methods

We conducted a prospective cohort study between December 2022, and January 2023. Early TCZ use referred to administration within 6 days after symptoms onset, while late TCZ use indicated administration after 6 days. The primary endpoint was 30-day mortality.

Results

Twenty-seven kidney transplant recipients with severe COVID-19 infection were enrolled, with 10 in the early use group and 17 in the late use group. In the early use group, ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP) and brain natriuretic peptide(BNP) levels had shown significant inhibitions comparing to the late use group, and those inflammatory cytokines demonstrated a noticeable decreasing trend after TCZ administration, whereas only CRP levels decreased in the late use group. The Kaplan-Meier survival curve demonstrated that the early use group had a higher likelihood of survival (P = 0.0078). Receiver Operating Characteristic (ROC) analyses revealed that the time from symptoms to TCZ use (AUC: 0.645), LDH (AUC: 0.803), CRP (AUC: 0.787), and IL-6 (AUC: 0.725) were potential predictive factors of TCZ efficacy. TCZ use within 6 days from symptoms onset, with CRP < 73.5 mg/L, LDH < 435.5 IU/L, and IL-6 < 103.5 pg/mL, had higher survival rates (P = 0.008, P = 0.009, P < 0.001, P < 0.001).

Conclusion

This study highlights the survival benefits of early TCZ use and the predicative role of cytokines levels in predicting TCZ efficacy in kidney transplant recipients with severe COVID-19 infection.

Introduction

Effective mobilization of Stem Cells(SCs) to peripheral blood (PB) is crucial for obtaining sufficient CD34⁺ cell numbers via apheresis. The ratio of pre-apheresis PB CD34⁺ cells is the best parameter for predicting the product CD34⁺ cell count. However, quantitating CD34⁺ PB cells requires flow cytometry, which usually takes two or more hours to obtain the results. We hypothesized that the product CD34⁺ cell count could be predicted using the counts of white blood cells (WBCs), mononuclear cells (MNCs), and pre-apheresis CD34⁺ cells. A formula that achieves this would substantially affect the efficiency and effectiveness of apheresis. We, therefore, aimed to estimate the number of CD34⁺ cells in the product using a formula that incorporates pre-apheresis PB WBC, MNC, and CD34⁺ cell counts and product WBC and MNC counts.

Methods

We examined the results of 373 leukapheresis procedures for SC mobilization. Effective separation of CD34⁺ PBSCs (count/μL) via apheresis was estimated using the following formula: [Product WBC (count/μL) × MNC (count/μL) × pre-apheresis CD34⁺ cell (percentage/μL)] ÷ [PB WBC count/μL × PB MNC (count/μL)].

Results

A strong correlation was observed between the CD34⁺ cell count calculated using our formula and the post-apheresis CD34⁺ cell count measured via flow cytometry (R = 0.939, based on linear regression analysis). In the subgroup analysis, this correlation was observed for all the disease subgroups and healthy donors.

Conclusion

We developed a formula that predicts the product CD34⁺ cell count and is useful for determining whether a second apheresis procedure will be required.

Background

The severity of complications after hematopoietic stem cell transplantation (HSCT) is dictated by the degree of immune reconstitution. However, the connection between immune reconstitution and the prognosis of pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. Therefore, the aim of this study was to evaluate the impact of lymphocyte subsets in children diagnosed with refractory or relapsed acute myeloid leukemia (R/R-AML) after allo-HSCT.

Methods

We retrospectively investigated the prognosis and lymphocyte subsets at d 90 (D90) post-allo-HSCT in 130 children diagnosed with R/R-AML between September 2019 and October 2022 at the Children's Hospital of Soochow University. Lymphocyte subgroups were assessed by flow cytometric analysis on D90 and compared among human leukocyte antigen (HLA)-matched sibling donor HSCT (MSD) (n = 14), haploidentical donor HSCT (n = 94), and HLA-matched unrelated donor HSCT (n = 22) groups. The associations between the counts and frequencies of lymphocyte subgroups and prognosis were assessed.

Results

In the MSD group, CD4+ T cell frequency and count were the highest (P < 0.001). Among the examined lymphocyte subsets, a lower proportion of CD4+ T cells (<14.535 %) at D90 correlated with a higher risk of cytomegalovirus infection (P = 0.002). A higher CD4+ T cell count (>121.39/μL) at D90 after HSCT was the single predictor of a lower fatality risk across all lymphocyte subgroups (univariate: P = 0.038 cut-off: 121.39/μL; multivariate: P = 0.036). No association with relapse was observed.

Conclusions

CD4+ T cell count may be used to identify pediatric patients with R/R-AML with a greater mortality risk early after HSCT.