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Donor specific antibodies (DSAs) are known as the leading cause of antibody mediated rejection (AMR), graft loss in kidney transplant (KT) recipients. DSAs characteristics, as immunoglobulin (Ig) classes, subclasses, and strength, are important to assess the immunological risk, early prediction of AMR, and therefor proper management. This longitudinal, case control study included 32 KT recipients at Assiut University Urology Hospital and 10 age and sex matched normal subjects as the control group. Total IgG, its subclasses and anti-human leukocyte antigen (anti-HLA) panel reactive antibody (PRA) were detected pre-transplantation (pre-TX), at 6-12- and 24-36-months post-TX. Rejection occurred in 4 recipients, 3 of them had high total IgG, IgG1 and/or IgG3. IgG2 and IgG4 were normal in all recipients. There were preformed anti-DSAs antibodies in 3/32 recipients (9.4%). Of these, two recipients became negative with no rejection occurred. The third recipient had high post-TX mean fluorescence intensity (MFI) and AMR occurred. The pre-TX PRA was negative in 29/32 recipients (90.6%). The PRA was negative in 8/29 recipients (27.6%) and the remaining 21/29 recipients (72.4%) developed de novo DSAs post-TX (MFI < 3000->10000). Rejection occurred with both low and high MFI. In 11 recipients, anti-HLA class I and II were not different between pre-TX, 3-6- and 24-36 months post-TX with no rejection occurred. The frequency and median levels of total IgG, IgG1 and IgG3 were increased in all recipients 24-36 months post-TX when compared with their levels pre-TX and 6-12 months post-TX in the 11 recipients and with the control group. The graft survival time significantly decreased in recipients with positive post-TX class I PRA. In conclusion, preformed DSAs may persist post-TX or turn negative. De novo DSAs developed post-TX even in non-sensitized recipients. Serum total IgG, IgG1 and IgG3 frequency increase 2-3 years post-TX., (Copyright© by the Egyptian Association of Immunologists.)

Background: Resistance to the action of rituximab (RTX) has been documented in several diseases. More recently, obinutuzumab (OBZ) has shown promise where RTX has failed in oncology and lupus nephritis. Unlike RTX, OBZ is a weak activator of complement, which may avoid the false-positive complement-dependent cytotoxicity (CDC) crossmatch tests after RTX infusions., Methods: The aim of this study was to explore the effect of OBZ on B-cell depletion in kidney-transplant candidates and its impact on crossmatch test results. We included 12 patients, who were either highly sensitized kidney-transplant candidates or kidney-transplant recipients presenting with antibody-mediated rejection. Six received OBZ, and 6 received RTX. CD-19 counts, flow cytometry, and CDC crossmatch tests were run immediately before and at 2 wk after drug infusion., Results: OBZ reduced CD-19 counts: median reduction was 98%. B-cell CDC crossmatch test results became positive following RTX infusion but were not affected by OBZ infusion., Conclusions: OBZ effectively depleted B-cell counts in sensitized kidney-transplant candidates and, unlike RTX, had no effect on CDC crossmatch results., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Given the uncertainty regarding the relationship between donor cells at microchimeric levels and its influence on graft function and clinical outcome, we explored the extent and importance of donor microchimerism in kidney transplantation. Twenty patients with chronic kidney disease who had received allografts from living donors were studied. We examined peripheral whole blood samples from the recipients one month after the transplant, applying mitochondrial DNA variant-specific polymerase chain reaction (PCR) to identify and quantify donor cells in relation to allograft function and survival during three years of follow-up. Higher quantities of donor-derived cell microchimerism in the peripheral blood correlated with better graft function in the early postoperative period at 1 month (R 2  = .536, p = .001) and predicted improved graft function 1 year following the transplant (R 2  = .430, p = .008). Furthermore, early post-transplant quantities of donor cell microchimerism were an important predictor of improved kidney function 3 years after transplantation (R 2  = .397, p = .021). However, donor cell microchimerism failed to predict patient and graft survival after 3 years (odds ratio = 0.536, p = .860). Our findings suggest that donor cell microchimerism plays an immunoregulatory role in kidney transplantation and contributes to donor-specific immune hypo-responsiveness and graft acceptance., (© 2020 John Wiley & Sons Ltd.)

Background: Polyomavirus nephropathy (PVN) mainly caused by BK polyomavirus (BKPyV) remains the most common productive viral infection of the kidney in immunosuppressed patients. The diagnosis of PVN is based on the detection of BK viruria and BK viremia in conjunction with histological findings in the graft biopsy., Methods: Our study was aimed to estimate the prevalence of productive BKPyV infection among renal transplant patients within the first year post-transplant and identify those at risk of developing PVN. Our cross-sectional study was conducted on 134 kidney transplant patients. Evidence of BKPyV replication was assessed by viral quantification of blood and urine samples of studied patients using a quantitative real-time polymerase chain reaction (Q-PCR)PCR), detection of decoy cells in urine cytology smears, histological examination of graft biopsies from Q-PCR BKPyV-positive patients, and immunohistochemical staining by simian virus 40 (SV40) antibody., Results: Significant BKPyV infection was prevalent in 8% (n = 11) of our patients, with a peak of BKPyV infection about 8 months post transplant. BKPyV viral load by Q-PCR assay in these patients varied from 1350 to 20,000,000 (1.35 × 10(3) to 2 × 10(7) ) copies/mL for urine samples and 935 to 18,920 (9.35 × 10(2) to 1.89 × 10(4) ) copies/mL for blood samples. All the 11 patients were positive for decoy cells but only 3 developed PVN based on histology and positive SV40 staining. BKPyV infection was more prevalent in older patients. All patients responded to reduction in their immunosuppressive regimens, apart from 2 patients who required replacement of calcineurin inhibitors-based regimen with mammalian target of ramapycin inhibitors with an overall good response., Conclusion: Protocol screening programs based on detection of viral replication by viruria, viremia, and decoy cells in urine are necessary to shed light on patients with high virus replication and hence increased risk of developing PVN, and to allow early diagnosis and intervention., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Donor specific antibodies (DSA) and a positive cross-match are contraindications for kidney transplantation. Trials of allograft transplantation across the HLA barrier have employed desensitization strategies, including the use of plasmapheresis, intravenous immunoglobulins, anti-B-cell monoclonal antibodies and splenectomy, associated with high-intensity immunosuppressive regimens. Our case 1 report suffered from repeatedly positive lymphocyte cross match after 1st renal transplantation. Graft nephrectomy could not correct the state of sensitization. Splenectomy was done in a trial to get rid of the antibody producing clone. Furthermore plasmapheresis with low dose IVIG could not as well revert the state of sensitization for the patient., Material and Methods: About 50 millions donor specific MSCs were injected to the patient., Results: MSCs transfusion proved to be the only procedure which could achieve successful desensitization before performing the second transplantation owing to their immunosuppressive properties., Conclusion: This case indicates that DS-MSCs is a potential option for anti-HLA desensitization. In cases 2 and 3 IV DS-MSCs transfusion was selected from the start as a successful line of treatment for pre renal transplantation desensitization to save other unnecessary lines of treatment that were tried in case 1., (© 2013 Blackwell Publishing Ltd.)