ABSTRACT
Background: B and T regulatory cells, also known as Bregs and Tregs, are involved in kidney transplantation. The purpose of this study is to monitor changes in the frequency and absolute numbers of Tregs (CD3+CD4+CD25+FoxP3+), transitional Bregs (tBregs) (CD24++CD38++), memory Bregs (mBregs) (CD24++CD27+), and plasmablasts before (T0) and six months (T6) after transplantation. Additionally, we aim to investigate any correlation between Tregs and tBregs, mBregs, or plasmablasts and their relationship with graft function. Methods: Flow cytometry was used to immunophenotype cells from 50 kidney recipients who did not experience rejection. Renal function was assessed using the estimated glomerular filtration rate (eGFR). Results: At T6, there was a significant decrease in the frequency of Tregs, plasmablasts, and tBregs, as well as in the absolute number of tBregs. The frequency of mBregs, however, remained unchanged. Graft function was found to have a positive correlation with the frequency of tBregs and plasmablasts. A significant correlation was observed between the frequency and absolute number of tBregs only when the eGFR was greater than 60 but not at lower values. At an eGFR greater than 60, there was a positive correlation between the absolute numbers of Tregs and mBregs but not between Tregs and tBregs. No correlation was observed for any cell population in dialysis patients. Conclusions: The data show a correlation between the frequency and absolute number of tBregs and the absolute number of Tregs and mBregs with good renal function in the early post-transplant period.
ABSTRACT
BACKGROUND: B cells have a significant role in transplantation. We examined the distribution of memory subpopulations (MBCs) and naïve B cell (NBCs) phenotypes in patients soon after kidney transplantation. Unsupervised machine learning cluster analysis is used to determine the association between the cellular phenotypes and renal function. METHODS: MBC subpopulations and NBCs from 47 stable renal transplant recipients were characterized by flow cytometry just before (T0) and 6 months after (T6) transplantation. T0 and T6 measurements were compared, and clusters of patients with similar cellular phenotypic profiles at T6 were identified. Two clusters, clusters 1 and 2, were formed, and the glomerular filtration rate was estimated (eGFR) for these clusters. RESULTS: A significant increase in NBC frequency was observed between T0 and T6, with no statistically significant differences in the MBC subpopulations. Cluster 1 was characterized by a predominance of the NBC phenotype with a lower frequency of MBCs, whereas cluster 2 was characterized by a high frequency of MBCs and a lower frequency of NBCs. With regard to eGFR, cluster 1 showed a higher value compared to cluster 2. CONCLUSIONS: Transplanted kidney patients can be stratified into clusters based on the combination of heterogeneity of MBC phenotype, NBCs and eGFR using unsupervised machine learning.
ABSTRACT
BACKGROUND: Chronic kidney disease is associated with immunological disorders, presented as phenotypic alterations of T lymphocytes. These changes are expected to be restored after a successful renal transplantation; however, additional parameters may contribute to this process. AIM: To evaluate the impact of positive panel reactive antibodies (PRAs) on the restoration of T cell phenotype, after renal transplantation. METHODS: CD4CD28null, CD8CD28null, natural killer cells (NKs), and regulatory T cells (Tregs) were estimated by flow cytometry at T0, T3, and T6 which were the time of transplantation, and 3- and 6-mo follow-up, respectively. Changes were esti mated regarding the presence or absence of PRAs. RESULTS: Patients were classified in two groups: PRA(-) (n = 43) and PRA(+) (n = 28) groups. Lymphocyte and their subtypes were similar between the two groups at T0, whereas their percentage was increased at T3 in PRA(-) compared to PRA(+) [23 (10.9-47.9) vs 16.4 (7.5-36.8 µ/L, respectively; P = 0.03]. Lymphocyte changes in PRA(-) patients included a significant increase in CD4 cells (P < 0.0001), CD8 cells (P < 0.0001), and Tregs (P < 0.0001), and a reduction of NKs (P < 0.0001). PRA(+) patients showed an increase in CD4 (P = 0.008) and CD8 (P = 0.0001), and a reduction in NKs (P = 0.07). CD4CD28null and CD8CD28null cells, although initially reduced in both groups, were stabilized thereafter. CONCLUSION: Our study described important differences in the immune response between PRA(+) and PRA(-) patients with changes in lymphocytes and lymphocyte subpopulations. PRA(+) patients seemed to have a worse immune profile after 6 mo follow-up, regardless of renal function.
ABSTRACT
BACKGROUND: Drug-induced hypersensitivity reactions attributed to the immunosuppressive agent tacrolimus after an organ transplant are rare in the literature. We present 3 cases of male adult patients grafted with a cadaveric liver who developed delayed hypersensitivity reactions to tacrolimus in the form of the prolonged-release capsules (Advagraf). Furthermore, the appropriate drug concentration solutions used for allergy testing are proposed. METHODS: All patients received a liver transplant (LT) because of cirrhosis of various etiologies. They were immunosuppressed with tacrolimus once daily. Several months after they had been placed on an immunosuppressive regimen with tacrolimus in the form of prolonged-release capsules (Advagraf), the patients presented with delayed hypersensitivity reactions and torturous pruritic rash that affected the whole body and was unresponsive to treatment with oral ursodeoxycholic acid, cholestyramine, or levocetirizine. Allergy testing that was performed by skin prick testing was negative. Nevertheless, intradermal testing yielded positive results in all 3 patients. Management was by interruption of the culprit agent, which was followed by symptom resolution. The immunosuppressive treatment was continued with alternative drugs. RESULTS: Appropriate nonirritating drug concentration solutions of the drug used for intradermal testing were highly sensitive and confirmed the clinical diagnosis of tacrolimus allergy in all the affected patients. CONCLUSION: Immunosuppressive treatment with tacrolimus in the form of prolonged-release capsules may cause a drug hypersensitivity reaction. A suspicion of allergy warrants a referral for allergy testing. Pruritic rash refractory to treatment in liver transplanted patients should be evaluated by an allergist for possible drug allergy when bile stasis and graft disease have been excluded. Intradermal testing has proven a highly sensitive method for confirming a drug allergy diagnosis, whereas skin prick testing did not.
