Investigating the Immunological Mechanisms Underlying Organ Transplant Rejection

Background: Therapeutic drug monitoring of immunosuppressant drugs are used to monitor drug efficacy and toxicity and to prevent organ transplant rejection. This study evaluates the analytical performance of semi-automated electrochemiluminescence immunoassays (ECLIA) for cyclosporine (CSA), tacrolimus (TAC) and sirolimus (SRL) on the Roche cobas e 411 analyzer at a major transplant hospital to assess method suitability and limitations. Methods: Residual whole blood samples from patients undergoing immunosuppressant therapy were used for evaluation. Imprecision, linearity, functional sensitivity, method comparisons and lot-to-lot comparisons were assessed. Results: Total imprecision ranged from 3.3 to 7.1% for CSA, 3.9 to 9.4% for TAC, and 4.6 to 8.2% for SRL. Linearity was verified from 30.0 to 960.9 μg/L for CSA, from 1.1 to 27.1 μg/L for TAC, and from 0.5 to 32.3 µg/L for SRL. The functional sensitivity met the manufacturer’s claims and was determined to be <6.5 μg/L for CSA, 1.1 μg/L for TAC, and <0.1 µg/L for SRL (CV≤20%). Deming regression analysis of method comparisons with the ARCHITECT immunoassay yielded slopes of 0.917 (95%CI: 0.885-0.949) and r of 0.985 for CSA, 0.938 (95%CI: 0.895-0.981) and r of 0.974 for TAC, and 0.842 (0.810-1.110) and r of 0.982 for SRL. Deming regression analysis of comparisons with the LC–MS/MS method yielded slopes of 1.331 (95%CI: 1.167-1.496) and r of 0.969 for CSA, 0.924 (95%CI: 0.843-1.005) and r of 0.984 for TAC, and 0.971 (95%CI: 0.913-1.030) and r of 0.993 for SRL. Conclusions: The cobas e 411 ECLIA for CSA, TAC, and SRL have acceptable precision, linearity, and functional sensitivity. The method comparisons correlated well with the ARCHITECT immunoassay and LC–MS/MS and is fit for therapeutic drug monitoring

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P0647ACUTE KIDNEY INJURY SECONDARY TO SUCROSE CONTAING INTAVENOUS IMMUNOGLOBULIN

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0647 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Sadiq Al Lawati ◽

Issa Al Salmi ◽

SUAD Hannawi

Keyword(s):

Acute Kidney Injury ◽

Serum Level ◽

Kidney Function ◽

Viral Infections ◽

Kidney Transplant Recipient ◽

Transplant Rejection ◽

Organ Transplant ◽

Vital Signs ◽

Kidney Injury ◽

Kaposi Sarcoma

Abstract Background and Aims Intravenous immunoglobulins (IVIG) are pooled polyvalent IgG antibodies extracted from the human plasma. While the initial indications were mainly immune deficiency states and some autoimmune diseases, the usage has been widened to include several immune mediated diseases, viral infections, and organ transplant rejection. Stabilizers in IVIG may include sugars, such as sucrose, glucose, or maltose. Sucrose in IVIG preparations may cause acute kidney injury. We report the case of a renal transplant patient who developed acute kidney injury due to sucrose nephropathy following the administration of sucrose containing IVIG. Method Four months after transplantation he was referred to our Hospital for deterioration of kidney function with eGFR (by MDRD formula) of 27ml/min. Cytomegalovirus virus (CMV) PCR turned positive (3300 copies/ml). Cyclosporine levels were high (C2: 2937 ng/ml) and hence, cyclosporine dose was adjusted. Induction therapy with Injection Ganciclovir for 2 weeks, followed by therapeutic dose of oral Valganciclovir was administered for the treatment of CMV infection. Skin examination revealed annular purple patches, suspicious of Kaposi Sarcoma, on the upper limbs. Skin biopsy confirmed the diagnosis. It was planned to give total IVIG of 2 gm/ kg in four daily divided doses. After completion of the second dose, serum creatinine increased to 370 µmol/L. He was clinically asymptomatic, euvolumic, vital signs were stable, and his urine output remained normal and his urinalysis was inactive. Results The ultrasound of the transplant kidney was normal with normal resistivity index. IVIG was stopped. He was well hydrated and underwent ultrasound guided biopsy. The graft biopsy showed acute tubular injury with flattening and vacuolation of tubular epithelial cells. Mitosis indicating tubular regeneration was seen. There was mild focal interstitial inflammation (20%) with mild lymphocytic tubulitis not amounting to graft rejection. Immunohistochemistry for C4d and polyomavirus (BKV) were both negative. The features were most consistent with sucrose induced nephropathy (Figure 1). Subsequent visits showed a decrease in BKV-PCR serum level and eventually undetected serum level of BKV-PCR at follow up about a month later. Conclusion In this paper, we presented a case of a living unrelated kidney transplant recipient who developed BKV nephropathy and developed impaired kidney function. The patient also had new onset diabetes mellitus after kidney transplantation (NODAT) but was otherwise in good general health. Treatment included sucrose containing IVIG. The patient subsequently developed acute kidney injury. The outcome was favorable with recovery of filtration rate to the baseline within 21 days without the need for dialysis. We conclude that the administration of sucrose containing IVIG may lead to acute kidney injury. We recommend the use of sucrose-free IVIG whenever possible. In all cases, caution is required when administrating IVIG.

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Granzymes and perforin in solid organ transplant rejection

Cell Death and Differentiation ◽

10.1038/cdd.2009.161 ◽

2009 ◽

Vol 17 (4) ◽

pp. 567-576 ◽

Cited By ~ 47

Author(s):

J C Choy

Keyword(s):

Transplant Rejection ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Solid Organ

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Discovery of CP-690,550: A Potent and Selective Janus Kinase (JAK) Inhibitor for the Treatment of Autoimmune Diseases and Organ Transplant Rejection

Journal of Medicinal Chemistry ◽

10.1021/jm1004286 ◽

2010 ◽

Vol 53 (24) ◽

pp. 8468-8484 ◽

Cited By ~ 203

Author(s):

Mark E. Flanagan ◽

Todd A. Blumenkopf ◽

William H. Brissette ◽

Matthew F. Brown ◽

Jeffrey M. Casavant ◽

...

Keyword(s):

Autoimmune Diseases ◽

Transplant Rejection ◽

Organ Transplant ◽

Janus Kinase ◽

Jak Inhibitor

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Risk of solid organ transplant rejection following vaccination with seasonal trivalent inactivated influenza vaccines in England: A self-controlled case-series

Vaccine ◽

10.1016/j.vaccine.2016.05.016 ◽

2016 ◽

Vol 34 (31) ◽

pp. 3598-3606 ◽

Cited By ~ 10

Author(s):

Gaël Dos Santos ◽

François Haguinet ◽

Catherine Cohet ◽

Dave Webb ◽

John Logie ◽

...

Keyword(s):

Transplant Rejection ◽

Organ Transplant ◽

Case Series ◽

Solid Organ Transplant ◽

Influenza Vaccines ◽

Solid Organ

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Antibody-Mediated Rejection in Solid Organ Transplant

AACN Advanced Critical Care ◽

10.4037/aacnacc2016366 ◽

2016 ◽

Vol 27 (3) ◽

pp. 316-323

Author(s):

Michael Petty

Keyword(s):

Immune System ◽

Transplant Rejection ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Solid Organ ◽

Antibody Mediated Rejection ◽

End Stage ◽

Transplanted Organs ◽

Broad Overview

Within a little more than a decade, the transplant of human organs for end-stage organ disease became a reality. The early barriers to successful long-term graft and patient survival were related to the inability to effectively control the immune system such that it would not attack the donor tissue but would still recognize and destroy invading organisms and cells. As immunosuppressive therapy has been refined and proper matching of donors and recipients has been improved, hyperacute rejection has become a rare occurrence and acute rejection has been markedly controlled. However, antibody-mediated rejection remains an important impediment to increased survival of transplanted organs. This article provides readers with a broad overview of the immune system, discusses mechanisms of transplant rejection, and details prevention, detection, and treatment of antibody-mediated rejection in solid organ transplant.

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