Background: Anti-PAR 1 (protease-activated receptor 1) and anti-ACE 2 (angiotensin 2-converting enzyme 2) antibodies are a kind of non-HLA (human leukocyte antigens) antibodies postulated to be of significance in autoimmunological diseases and organ transplantation. Methods: We assessed anti-PAR 1 and anti-ACE 2 antibody levels in patients with membranous nephropathy n= 18, focal and segmental glomerulosclerosis (FSGS) n = 25, lupus nephritis (LN) n = 17, IgA nephropathy n = 14, mesangial proliferative (non-IgA) glomerulonephritis n = 6, c-ANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) vasculitis n = 40, p (perinuclear)-ANCA vasculitis n = 16, and compared them with a healthy control group n = 22. Next, we observed the clinical course of the patients (creatinine, total protein, and albumin) up to 2 years and correlated the results with the level of antibodies. Results: The anti-PAR 1 antibody level was lower in membranous nephropathy and FSGS compared to the control group. Anti-PAR 1 antibody levels were higher in secondary compared to primary glomerulonephritis. Both anti-PAR 1 and anti-ACE 2 antibody levels correlated positively (in focal and segmental glomerulosclerosis) or negatively (in lupus nephritis) with total protein and albumin at different time points of observation. Anti-PAR 1 and anti-ACE 2 antibody levels correlated also with creatinine level at one time point of observation in IgA nephropathy. Anti-PAR 1 and anti-ACE 2 antibodies correlated with each other in membranous nephropathy, FSGS, and p- and c-ANCA vasculitis (p < 0.05). Conclusions: The anti-PAR 1 antibody level was lower in membranous nephropathy and focal and segmental glomerulosclerosis compared to the control group. Anti-PAR 1 antibody levels tend to be higher in secondary compared to primary glomerulonephritis.

Donor-derived cell-free DNA (dd-cfDNA) is an emerging non-invasive biomarker of kidney allograft injury. Elevated dd-cfDNA has been associated with acute rejection, particularly antibody-mediated rejection; however, dd-cfDNA reflects graft-derived tissue injury rather than a specific alloimmune mechanism. Its interpretation may therefore be challenging in conditions characterized by endothelial and microvascular injury, such as atypical hemolytic uremic syndrome (aHUS). This retrospective observational study included 14 kidney transplant recipients who underwent their first kidney transplantation at Wroclaw Medical University between April and December 2022. Twelve non-aHUS recipients with stable renal function and two recipients with aHUS were assessed. Plasma samples were collected at four early post-transplant time points: day 7 (D7), day 14 (D14), month 1 (M1), and month 2 (M2). dd-cfDNA was measured using next-generation sequencing with the AlloSeq cfDNA assay. Donor-specific anti-HLA antibodies (DSA) were assessed using single-antigen bead testing. In non-aHUS recipients, median %dd-cfDNA declined from 0.72% [0.28%, 2.33%] at D7 to 0.12% [0.05%, 0.34%] by M1. In contrast, recipients with aHUS demonstrated persistently elevated dd-cfDNA values fluctuating around 1% [0.88%, 1.14%] during the first month of follow-up. No DSA were detected in any patient during the observation period. No apparent correlation was observed between %dd-cfDNA and serum creatinine in this small cohort. In this preliminary observational study, kidney transplant recipients with aHUS showed persistently elevated early post-transplant dd-cfDNA despite the absence of detectable DSA, absence of clinically documented rejection, and preserved graft function during follow-up. These findings suggest that universal dd-cfDNA thresholds may require cautious interpretation in aHUS. Larger biopsy-anchored studies integrating complement and endothelial injury markers are needed to clarify whether dd-cfDNA elevation in aHUS reflects alloimmune injury, complement-mediated microvascular injury, or overlapping mechanisms.

EFR3A is a conserved peripheral membrane protein required for the plasma membrane localization of the phosphatidylinositol-4 kinase (PI4KIIIα/PI4KA) complex and for regulating the responsiveness of G-protein-coupled receptors. Additionally, it was implicated in several other potentially unrelated physiological functions. In metazoan organisms, EFR3A is ubiquitously co-expressed with its paralog EFR3B which shares similar biological roles. This brief review summarizes the current knowledge regarding the potential roles of EFR3A in human disease states, including neurological and cardiovascular disorders, as well as various neoplasia-based diseases.

Background: The complement system factors’ role in the pathogenesis of autoimmunological diseases is known, but the influence of autoantibodies against complement factors’ receptors on the course of specific glomerular diseases remains unclear. Methods: We measured the levels of anti-C3aR and anti-C5aR antibodies in patients with membranous nephropathy (n = 18), primary focal and segmental glomerulosclerosis (FSGS) (n = 25), lupus nephritis (LN) (n = 17), IgA nephropathy (n = 14), mesangial proliferative (non-IgA) glomerulonephritis (n = 6), c-ANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) vasculitis (n = 40), and p (perinuclear)-ANCA vasculitis (n = 16). These conditions were compared to a healthy control group (n = 22). Then, for up to two years, we tracked the patients’ clinical progress (in terms of creatinine, total protein, and albumin levels) and compared the outcomes with their antibody levels. Results: The lupus nephritis group had higher levels of anti-C3aR and anti-C5aR antibodies than the other groups. The lupus nephritis group’s anti-C3aR antibody level showed a negative correlation with albumin and total protein at several time points of observation. Additionally, at numerous observational points, the anti-C3aR antibody level showed a positive correlation with both the basic albumin level in the FSGS group and the total protein level. Conclusions: The anti-C3aR and anti-C5aR antibodies are higher in lupus nephritis patients compared to other glomerulonephritis patients and healthy individuals. Albumin and total protein levels appear to be correlated positively with anti-C3aR antibody levels in FSGS and negatively in lupus nephritis.

Background: PAR 1 (protease-activated receptor 1) and endothelin 1 are biomarkers that could be of significance in kidney diseases. Methods: We measured the plasma levels of PAR1 and endothelin 1 in patients with membranous nephropathy (n = 19), focal and segmental glomerulosclerosis (FSGS) (n = 30), systemic lupus erythematosus (SLE) (n = 22), IgA nephropathy (n = 16), mesangial proliferative (non-IgA) glomerulonephritis (n = 7), chronic kidney disease (CKD) (n = 27), and hemodialysis (n = 26), as well as a healthy control group (n = 22). Then, for two years, we tracked the patients’ clinical progress (creatinine, total protein, and albumin levels) and compared the outcomes with their initial PAR 1 and endothelin 1 levels. Moreover, we checked the correlations between PAR 1 and endothelin 1 and the results of anti-PAR1 and anti-ETAR (endothelin A receptor) evaluations. Results: Membranous nephropathy, FSGS, IgA nephropathy, CKD, and hemodialysis patients had higher PAR 1 levels than the control group. PAR 1 correlated with total protein, albumin in SLE, total protein in IgA nephropathy, and creatinine in CKD. Endothelin 1 correlated with albumin in membranous nephropathy, total protein, albumin, creatinine in FSGS, total protein in IgA nephropathy, total protein, and albumin in CKD. PAR 1 correlated with anti-PAR 1 in FSGS. Anti-ETAR correlated with anti-PAR 1 in membranous nephropathy, FSGS, and IgA nephropathy. Conclusions: PAR 1 levels are elevated in some kidney diseases compared to the healthy population. Both PAR 1 and endothelin 1 are supposed to be related to the clinical course of specific kidney diseases.

Introduction: Non-HLA autoantibodies directed against G protein-coupled receptors (GPCRs) have emerged as potential contributors to endothelial activation, vascular injury, rejection, and chronic allograft dysfunction after kidney transplantation. Protease-activated receptors 1 and 2 (PAR1 and PAR2) are GPCRs located at the interface of coagulation, inflammation, endothelial signaling, and tissue remodeling. However, the clinical relevance of circulating anti-PAR1 and anti-PAR2 autoantibodies in kidney transplant recipients remains undetermined. Methods: We performed a retrospective observational study including 123 kidney transplant recipients who underwent clinically indicated allograft biopsy between 2018 and 2025. The primary objective was to evaluate associations between serum anti-PAR1 and anti-PAR2 autoantibody concentrations and the severity of Banff histopathological lesions. Associations with rejection phenotypes, selected clinical variables, and graft outcomes were also evaluated. Antibody concentrations were measured by ELISA. Correlation analyses, non-parametric group comparisons, logistic regression models, and exploratory landmark analyses of death-censored graft survival from serum sampling were performed. Correction for multiple testing was applied using the Benjamini–Hochberg false discovery rate procedure. Results: Anti-PAR2 concentrations showed weak but statistically significant associations with interstitial fibrosis (Kendall τ = 0.221, pFDR = 0.005), tubular atrophy (Kendall τ = 0.216, pFDR = 0.005), arteriolar hyalinosis (Kendall τ = 0.193, pFDR = 0.018), and total inflammation (Kendall τ = 0.226, pFDR = 0.005). Borderline associations were observed for peritubular capillaritis, transplant glomerulopathy, and inflammation in areas of interstitial fibrosis and tubular atrophy (all pFDR = 0.052). No histopathological associations remained significant for anti-PAR1. Both anti-PAR1 and anti-PAR2 concentrations varied with time from transplantation to biopsy, while anti-PAR2 was additionally associated with recipient age at transplantation. Neither antibody was significantly associated with rejection phenotypes. In the exploratory landmark analysis, anti-PAR2 concentrations above the cohort median were associated with a higher hazard of death-censored graft loss (HR = 2.136, 95% CI 1.202–3.795; p = 0.010). Discussion: Higher anti-PAR2 autoantibody concentrations were weakly associated with several chronic histological lesion scores in kidney allograft biopsies. An exploratory landmark analysis showed poorer death-censored graft survival among recipients with anti-PAR2 concentrations above the cohort median, although this association was not significant when anti-PAR2 was analyzed continuously. These findings require prospective validation.