Background: The clinical relevance of circulating B-cell subpopulations during the early period after kidney transplantation remains incompletely understood. Methods: In this prospective single-center study, frequencies and absolute numbers of peripheral B-cell subpopulations were longitudinally assessed by flow cytometry in 71 kidney transplant recipients before transplantation (T0) and at 3 (T3), 6 (T6) and 12 months (T12) post-transplant. Associations with graft function, rejection episodes and clinical variables were explored. Results: During the first post-transplant year, relative frequencies of total and naïve B cells declined, whereas absolute counts showed modest increases. Memory B-cells expanded over time, driven by both class-switched (CSBC) and class-non-switched (CNSBC) subsets. Transitional regulatory B cells (tBregs) and plasmablasts decreased significantly, while memory regulatory B cells (mBregs) remained stable. Pre-transplant B-cell profiles did not differ between recipients experienced rejection and those with stable graft function. At T12, rejection was associated with a shift toward a memory-dominant peripheral profile, characterized by reduced naïve representation. tBregs showed modest positive associations with graft function during follow-up. Hierarchical clustering identified naïve- and memory-dominant phenotypes representing distinct post-transplant immune compositions. Conclusions: Early post-transplant peripheral B-cell landscapes are dynamic and heterogeneous. Peripheral B-cell phenotyping shows limited value as a standalone clinical monitoring tool.

Antibody-mediated rejection (AMR) remains a major cause of kidney allograft injury and loss. Although donor-specific antibodies against human leukocyte antigens (HLA-DSAs) are central to humoral alloimmunity, they do not explain all cases of microvascular inflammation or graft dysfunction. This review critically evaluates non-HLA antibodies as potential mediators of allograft injury and markers of dysregulated humoral immunity by integrating functional, experimental, clinicopathological, and clinical evidence. Receptor-targeting antibodies, especially those against the angiotensin II type 1 receptor (AT1R) and the endothelin-1 type A receptor (ETAR), have the strongest evidence for direct pathogenicity. Antibodies against major histocompatibility complex class I-related chain A (MICA) and glutathione S-transferase theta-1 (GSTT1) reflect non-HLA alloimmunity, whereas antibodies targeting perlecan-derived LG3, vimentin, and injury-associated antigens may arise through secondary autoimmunity and mark broader humoral activation. We propose that selected pathogenic non-HLA antibodies participate in a feed-forward cycle of graft injury, antigen exposure, epitope spreading, and humoral amplification, although this model requires longitudinal validation. Crucially, non-HLA antibody positivity alone should neither establish AMR nor guide antibody-specific treatment. Its interpretation should be target-specific and integrated with HLA-DSAs, histopathology, molecular findings, graft function, and evidence of immune activation.

Background: Post-transplant immune heterogeneity may influence kidney allograft outcomes, yet the clinical relevance of circulating T-cell phenotypes remains incompletely defined. We aimed to identify 12-month post-transplant data-driven T-cell clusters and examine their relation to graft-function patterns during the first post-transplant year. Methods: Peripheral blood T-cell subpopulations were analyzed in 112 kidney transplant recipients at 12 months post-transplantation using flow cytometry. Standardized subpopulation frequencies underwent unsupervised hierarchical clustering, with principal component analysis used for visualization. Longitudinal graft function trajectories (eGFR and serum creatinine at 1, 3, 6, and 12 months) were analyzed using generalized estimating equation models, including time-by-cluster interactions. Results: Three recipient clusters were identified: a CD8-skewed cytotoxic/senescent cluster, an innate-like cytotoxic cluster, and a CD4-dominant cluster. Cluster robustness was supported by complementary k-means analysis. Older recipient age and baseline cytomegalovirus seropositivity were associated with the CD8-skewed cluster. Recipients assigned to different T12 clusters showed differences in serum creatinine levels and graft function trajectories, although some associations were attenuated after additional adjustment for transplant-related factors. Conclusions: In this cohort, unsupervised clustering identified distinct post-transplant T-cell profiles associated with early graft function patterns. These findings are hypothesis-generating and require longitudinal and external validation.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease (ESRD) globally. Beyond metabolic and haemodynamic stress, the complement system has emerged as a contributor to glomerular and tubulointerstitial injury. In type 1 diabetes mellitus (T1DM), complement proteins contribute through autoimmune mechanisms, while in type 2 diabetes mellitus (T2DM) they are linked to insulin resistance. In both, complement activation promotes micro- and macrovascular complications through inflammatory pathways that accelerate DN progression. This review summarises the current evidence on the role of complement activation in diabetic nephropathy (DN). First, we outline the mechanisms by which the complement system is activated through the lectin pathway (in which mannoses bind to modified glycosylation structures), the classical pathway (in which C1q recognises immune complexes/damaged self), and the alternative pathway (in which C3 ticks over and amplifies on damaged renal surfaces). Next, we consider the roles of their effector molecules (C3a, C5a, and C5b-9/MAC), and the consequences of regulatory dysfunction (e.g., CD59 dysfunction). When integrated with findings from renal histology, blood and urine biomarkers enable us to evaluate the correlation between prognosis, disease severity, and progression. We will also discuss therapeutic implications, including the rationale behind selective complement inhibition and future intervention strategies.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread immune dysregulation and the production of autoantibodies targeting nuclear, cytoplasmic, and cell surface antigens. These autoantibodies are central to disease pathogenesis, contribute to immune complex formation and organ damage, and serve as essential diagnostic and prognostic markers. Their detection supports disease classification, guides clinical decision-making, and offers insight into disease activity and therapeutic response. Traditional markers such as anti-nuclear antibodies (ANA), anti-dsDNA, and anti-Sm antibodies remain diagnostic cornerstones, but growing attention is given to anti-C1q, anti-nucleosome antibodies (ANuA), anti-ribosomal P, antiphospholipid, and anti-cytokine antibodies due to their associations with specific disease phenotypes and activity. These markers may reflect disease activity, specific organ involvement, or predict flares. The mechanisms underlying their persistence include B cell tolerance failure and long-lived plasma cell activity. The aim of this review is to summarize current knowledge on the major autoantibodies in SLE, appraise available detection methods, highlight their clinical utility and limitations and present evidence on the association between antibodies and disease phenotypes.

Objectives/Background: B lymphocytes are involved in both graft function and rejection. The role of double-negative (DN) and marginal zone B (MZB) lymphocytes in transplantation remains unclear. This study aims to investigate their role one year after transplant. Methods: The frequency and absolute numbers of DN and MZB cells were determined by flow cytometry before transplantation and at 3, 6 and 12 months after transplant. They were correlated with graft function and rejection. Results: Both the frequency and absolute number of MZB and DN cells increased 12 months after transplantation. Variations were observed in the populations studied at different time points. The observed decrease in the frequency of MZB lymphocytes in kidney recipients with rejection at 12 months, the end of follow-up, was associated with rejection episodes. On ROC curve analysis, a cut-off value of <20.6% could be a predictor of rejection risk in the first 12 months after transplantation (sensitivity 72.7%, specificity 69.6%). No relationship was found between the frequencies and absolute numbers of cell populations and graft function at any time point. Conclusions: The kinetics of B cells (DN and MZB) were determined over the course of 12 months after kidney transplantation. The frequency of MZ B cells was associated with rejection episodes.

Pancreaticoduodenectomy is the standard surgical treatment for a range of malignant and some benign diseases. The mortality rate associated with this procedure has decreased to less than 3% in recent years, although the morbidity remains high at 6–40%. Common complications may include delayed gastric emptying, pancreatic fistula, intra-abdominal abscess, and gastrointestinal or intra-abdominal bleeding, among others. Bleeding and pseudoaneurysm formation are likely to be the most significant complications. This is a case report about gastrointestinal bleeding following a Whipple procedure from an aberrant hepatic artery originating from the superior mesenteric artery (SMA), treated by endovascular means. The SMA was cannulated under local anesthesia and direct puncture of the common femoral artery. Catheterization and angiogram of the aberrant right hepatic artery identified the pseudoaneurysm and bleeding site at its bifurcation. Coil embolization resulted in pseudoaneurysm occlusion and bleeding management. Hepatic perfusion was not affected as the main vasculature of the liver, namely the common hepatic artery, remained intact. The management of hemorrhage following pancreatectomy represents a significant challenge, particularly given the vulnerability of the patient cohort and the necessity for re-operation in an anatomically challenging environment. Endovascular intervention is the preferred method of treatment when applicable, as it can be performed under local anesthesia and is associated with less morbidity.

Background/Aim: Fibrillary glomerulonephritis (FGN) is a rare glomerular disease characterized by non-amyloid fibrillary deposits in the glomeruli and positive staining for DNAJB9. There is currently no treatment of choice, and the poor prognosis highlights the need for further research. We aimed to investigate the clinical and pathological characteristics and outcomes of FGN patients from a tertiary nephrology center. Methods: A retrospective cohort study of eleven patients diagnosed with FGN between 2016 and 2025, based on kidney biopsy and DNAJB9 positivity, was used. Partial response was defined as a ≥50% reduction in proteinuria with stable renal function. Results: At diagnosis, nine patients had nephrotic-range proteinuria, and eight had microscopic hematuria. Mean serum creatinine was 1.6 mg/dL, and mean proteinuria was 3.78 g/24 h. Comorbidities included SLE (n = 1), sarcoidosis (n = 1), and lung cancer (n = 1). The most common histological pattern was mesangial proliferative (n = 6). DNAJB9 staining was positive in five patients. All patients received RAAS blockade and immunosuppression (e.g., corticosteroids, rituximab). Partial response occurred in 73% with a median follow-up of 24 months, with 80% showing >50% proteinuria reduction. One patient died during follow-up; no patients progressed to ESRD or required dialysis. Conclusions: FGN is clinically diverse and lacks a standard treatment. The small sample size limits generalizability.

Background: Detailed characterization of B cells in dialysis patients who are candidates for kidney transplant is still lacking, with little information on how dialysis duration and modality impact B cell subsets. Methods: Cluster analysis of flow cytometry determined the frequencies and absolute numbers of B-cell subsets and divided the cohort of 78 candidates into two distinct clusters, one with shorter and one with longer dialysis duration. Results: The immune profiles of the clusters differed depending on whether frequencies or absolute counts were considered. In long-term dialysis patients, the frequency of total memory, double negative and marginal zone B cells increased, while the frequency of naive and regulatory B cells decreased. This pattern was reversed in short-term dialysis patients, with a decrease in memory and an increase in naive and regulatory populations. The B subset number decreased significantly in long-term dialysis patients, while it increased significantly in short-term dialysis patients. The dialysis modality affected the frequency-based subset immune profiles. Conclusions: It is important to determine whether the evaluation is based on frequencies or absolute numbers. The different distribution of B cell subsets in the clusters, in terms of frequencies and absolute numbers, was influenced by dialysis duration. Modality and age only influenced the frequencies.

Background/Objectives: The purpose of this study was to evaluate numerical changes in immune cells after successful kidney transplantation and associate their recovery with clinical and laboratory factors. Methods: In 112 kidney transplant recipients, we performed flow cytometry to evaluate counts of CD4+, CD8+, and regulatory T cells (Tregs), as well as natural killer (NK) cells, before kidney transplantation (T0) and three (T3), six (T6), and twelve (T12) months later. The results were associated with the recipient’s age, cold ischemia time (CIT), the type of donor, dialysis method and vintage, and graft function in one year. Results: Total and CD8+ T cell counts increased gradually one year post transplantation in comparison with pre-transplantation levels, whereas the number of CD4+ T cells and Tregs increased, and the number of NK cells decreased in the first three months and remained stable thereafter. The recipient’s age was negatively correlated with total, CD4+, and Treg counts at T12, whereas CIT affected only total and CD4+ T cell count. Moreover, recipients receiving kidneys from living donors presented better recovery of all T cell subsets at T12 in comparison with recipients receiving kidneys from cadaveric donors. Patients on peritoneal dialysis had increased numbers of total and CD8+ T cells, as well as NK cells. Finally, estimated glomerular filtration rate was positively correlated with Treg level and potentially CD4+ T cells one-year post transplantation. Conclusions: Successful kidney transplantation results in the recovery of most T cell subsets. Lower recipient age and better graft function contribute to increased T cell counts, whereas donor type and dialysis modality are the most important modifiable factors for optimal immune recovery.

Rheumatoid arthritis (RA) is a well-known autoimmune inflammatory disease that affects the diarthrodial joints. Inflammation increases the production of reactive oxygen species (ROS), which may explain why RA is one of the diseases that induce oxidative stress. This study aimed to evaluate the potential differences in biochemical, hematological, and oxidative stress markers in the early stages of RA and after different treatment regimens. The study involved 111 patients, 28 men and 83 women aged 34 to 59 years, who were divided based on their c-reactive protein (CRP) levels into inactive RA patients (IRA) with CRP < 1.3 (n = 57, 22 men and 35 women) and active RA patients (ARA) with CRP ≥ 1.3 (n = 54, 6 men and 48 women). The study participants were divided into two groups, A and B, based on their treatment regimen. Group A, 90% of which were IRA patients, received methotrexate (MTX) monotherapy. Group B, which comprised 90% ARA patients, received a combination of leflunomide, a conventional disease-modifying antirheumatic drug (DMARD), and a biologic DMARD. The hematological, biochemical, oxidative stress, and RA-specific biomarkers were measured twice in groups A and B in the early stage of the disease, before and 3 months post-treatment, using conventional colorimetric, fluorometric, and immunological assays. According to the results of our study, glutathione peroxidase (GPx), ROS, calcium (Ca) and phosphorus (P) ions, vitamin C and D, and lipid profiles could serve as potential diagnostic markers in the early stages of the disease. Both treatment options were equally effective at improving the overall health of the patients. However, treatment resulted in a further increase in ROS levels and a decrease in antioxidant markers.

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.

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.

The Immune System (IS) and Kidney function are closely and interactively connected. IS dysfunction happening in autoimmune diseases, infections, malignancies, etc. is implicated in the pathogenesis of kidney involvement, leading to a great spectrum of glomerular and interstitial injury through several immunological pathways, such as immune complex deposition, activation of complement and signaling pathways. Complications of chronic kidney disease (CKD), including accumulation of uremic toxins, O2 free radicals, advanced glycation end products, increased expression of Toll Like Receptors on monocytes, cytokine overproduction, result in a situation characterized by chronic inflammation combined with premature ageing, and usually designated as “inflamm-aging”, followed by detrimental clinical consequences in CKD patients, such as increased cardiovascular risk, susceptibility to infections and malignancies. Kidney transplant can potentially restore the immune profile of patients, albeit immunosuppression treatment may be followed by further complications. The presence of certain T cell subsets at time of renal transplantation may affect response to immunosuppression and acute or chronic rejection, suggesting that patients’ immune profile at time of transplantation may have substantial impact in short and long term graft function.

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.

Introduction: Changes which happen on the phenotype of T lymphocytes during chronic kidney disease CKD, include reduction of CD4CD25FoxP3(Tregs) and increase in CD28null and CD16CD56(NKs) cells. These alterations are expected be restored following kidney transplantation. Patients-Methods: In this prospective study, we included patients with CKD (Ν=71), who were transplanted and followed for up to 12 months. The same immunosuppressive protocol was used to all patients, including steroids, Calcineurine inhibitors and mycophenolate mofetil, with or without ATG. Cytometric analysis was performed at time point T0 (day of transplantation) and, then at Τ3, Τ6, Τ12 (3,6,12 months after transplantation, respectively), to estimate the phenotype of T lymphocytes. Based on this analysis T lymphocyte subtypes studied were: CD4, CD8, CD4CD28null, CD8CD28null, NKs, Tregs. Results: A remarkable and sustained increase in the population of total lymphocytes, as well as of CD4 [510(331), 764(606), 857(661), p<0.0001], CD8 [290(188), 434(318), 528(312), p<0.0001], NKs [198(152), 126(134), 142(152), p<0.001) and Tregs [21(18), 24(20), 34(26), p<0.001], was noticed at time points T0-T3-T6, respectively. All subpopulations remained stable thereafter, during the time period T6-T12. At time point T0, patients who had been on chronic hemodialysis (HD) (N=64) had significantly reduced numbers of Tregs, compared to those undergoing Pre-emptive transplantation (N=7), p=0,006, and increased number of CD8CD28null cells (p=0.006). Furthermore, Treg population had significantly negative correlation with dialysis vintage, r=-0.5, p=0.004.At time point Τ12, Treg population had significant correlation with previous HD, delayed graft function (DGF) and administration of ATG, (p=0.02, p=0.004, p=0.04, respectively. CD8CD28null cells had significant correlation only with the presence of positive Panel Reactive Antibody, p=0.04. Conclusions: The beneficial effect of renal transplantation was prompt and evident mainly in the subpopulations of regulatory T cell and NKs, especially in patients undergoing Pre-emptive transplant, however the detrimental effect of HD on CD8 molecule did not seem to be restored during the 12 month period of follow up.