TRAnscriptional Profile of Peripheral Blood Cells in Patient With Chronic Kidney and Lung Rejection: Correlation With Response to Extracorporeal Photo-aphereSiS: : Studio Osservazionale-ambispettico.

Antibody-mediated chronic rejection (AMCR) is the leading cause of kidney graft loss. On average, more than 50% of patients resume dialysis within two years of diagnosis. The prevalence of AMCR reported in the literature varies, reaching up to 30%. The causes of chronic humoral rejection are not yet fully understood; however, its mechanism is based on donor-specific antibodies (DSAs), which may appear in the patient's serum and play a critical role. It remains unclear whether different inflammatory stimuli and/or inadequate immunosuppression induce their formation.

AMCR-related damage develops insidiously and often progresses rapidly to end-stage renal failure, with the onset of nephrotic-range proteinuria. For several years, it has been possible to detect and monitor DSAs in patient serum using the Luminex technique (LSAB: Luminex single antigen beads), which offers extremely high sensitivity and specificity.

De novo DSAs (dnDSAs) have been reported in 12-19% of kidney transplant recipients, and in 63% of cases their presence is associated with histological features of chronic rejection, high levels of proteinuria, and a rapid decline in glomerular filtration rate (GFR). It has been estimated that the reduction in GFR is four times greater in patients with dnDSAs than in age-matched transplant recipients without dnDSAs. Some authors report that even low dnDSA levels (MFI < 1000) are predictive of poor outcomes. The unfavorable prognosis associated with dnDSAs appears to depend on their ability to fix complement (C1q, C4d, and C3d), which confers increased cytotoxicity.

The diagnostic criteria for AMCR, revised at the 2013 Banff meeting, are threefold: (i) morphological evidence of chronic rejection in tissue, (ii) evidence of antibody interaction with the vascular endothelium, and (iii) serum positivity for DSAs.

Currently, there is no effective therapy for chronic humoral rejection, and there is broad consensus within the scientific community that prevention-through optimal organ allocation and adequate immunosuppressive regimens-remains the only viable strategy. Most published studies describe small patient cohorts treated with steroids and/or rituximab (RTX), high-dose intravenous immunoglobulin (IVIG), plasmapheresis (PHP), and/or bortezomib (BTZ) in addition to standard therapy. None of these treatments has demonstrated proven efficacy, while an increased risk of infection has been consistently reported.