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Table of Contents
CASE REPORT
Year : 2019  |  Volume : 13  |  Issue : 3  |  Page : 234-235

Successful renal transplantation in a patient with perinuclear antineutrophil cytoplasmic antibody-associated vasculitis with chronic kidney disease with complement-dependent cytotoxicity crossmatch positivity (autoantibody induced) and donor-specific antibodies and flow cytometry crossmatch negative


Department of Nephrology, IKDRC ITS Civil Hospital, Ahmedabad, Gujarat, India

Date of Submission30-Jun-2017
Date of Decision25-Jun-2018
Date of Acceptance29-Jul-2018
Date of Web Publication17-Sep-2019

Correspondence Address:
Dr. G S Kasat
Department of Nephrology, IKDRC ITS Civil Hospital, Ahmedabad, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_32_17

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  Abstract 


The positive complement-dependent cytotoxicity crossmatch (CDCXM) is considered as a contraindication for renal transplantation (RT) since long in an effort to avoid immediate rejection. There has been tremendous development in our understanding of transplant immunology today, and more sensitive and specific methods such as flow cytometry crossmatch (FCXM) and solid-phase antibody screening are used for detailed immunological assessment. We report successful RT in a 23-year-old girl with end-stage renal disease due to vasculitis on dialysis for 2 years. Before transplantation, the patient had Anti Human Globulin CDCXM positive while Dithioerythritol (DTT)-CDCXM was negative. The patient had no donor-specific antibodies examined by Luminex single-antigen beads and her FCMXM was negative. In the posttransplant period, there was no evidence of immune injury. Her serum creatinine was 0.7 mg/dl on the 3rd posttransplant day at the time of discharge. Induction immunosuppression was rabbit thymoglobulin (1.5 mb/kg) and methylprednisolone (500 mg, 3 doses) and maintenance immunosuppression was tacrolimus + prednisolone + mycophenolic acid. We found that even though CDCXM positivity has been traditionally considered as a contraindication for renal transplantation, in few carefully selected patients, we can still proceed to renal transplantation even if CDCXM is positive if more advanced and robust immunological tools such as FCMXM and donor-specific antibodies are negative. In our patient, AHG-CDCXM was positive while DTT-CDCXM was negative making it clear that antibodies of IgM origin were probably responsible for CDCXM positivity.

Keywords: Complement-dependent cytotoxicity crossmatch, donor-specific antibodies, flow cytometer crossmatch, renal transplantation


How to cite this article:
Kasat G S, Patel J C, Patil M V, Kumar D P, Kute V B, Shah P R, Patel H V, Modi P R, Shah V R, Trivedi V B, Trivedi H L. Successful renal transplantation in a patient with perinuclear antineutrophil cytoplasmic antibody-associated vasculitis with chronic kidney disease with complement-dependent cytotoxicity crossmatch positivity (autoantibody induced) and donor-specific antibodies and flow cytometry crossmatch negative. Indian J Transplant 2019;13:234-5

How to cite this URL:
Kasat G S, Patel J C, Patil M V, Kumar D P, Kute V B, Shah P R, Patel H V, Modi P R, Shah V R, Trivedi V B, Trivedi H L. Successful renal transplantation in a patient with perinuclear antineutrophil cytoplasmic antibody-associated vasculitis with chronic kidney disease with complement-dependent cytotoxicity crossmatch positivity (autoantibody induced) and donor-specific antibodies and flow cytometry crossmatch negative. Indian J Transplant [serial online] 2019 [cited 2019 Dec 11];13:234-5. Available from: http://www.ijtonline.in/text.asp?2019/13/3/234/266947




  Introduction Top


Since five decades, complement-dependent cytotoxicity crossmatch (CDCXM) has been considered an important tool to assess the immunological risk, wherein the recipient's plasma is incubated with donor lymphocytes in the presence of complement factors.[1] A positive CDCXM has been traditionally considered a contraindication to renal transplantation. This pioneering work was done by Terasaki and Patel in 1969.[2],[3] Since then, tremendous progress has been made in transplant immunology.

In 1978, at the conference of the American Engineering Foundation in Pensacola, Florida, the design of flow cytometer was approved and still later solid-phase antibody screening was developed which are more sensitive and specific than CDCXM.

This is a case report of successful kidney transplantation in a patient who had positive complement-dependent crossmatch because of autoantibodies and negative flow cytometry crossmatch (FCXM) and she was devoid of donor-specific antibodies.


  Case Report Top


A 23-year-old female patient developed peripheral antineutrophil cytoplasmic antibody-associated vasculitis with end-stage renal disease. She was on maintenance hemodialysis through left brachiocephalic fistula twice per week for 1 year. She was admitted for RT with cross donor in view of ABO incompatibility with mother.

Lymphocyte crossmatching was performed using AHG-CDCXM 80% (positive). Auto crossmatching was done which was 50% (positive). Dithioerythritol (DTT) was used to treat recipient's serum to exclude IgM antibodies; DTT-CDCXM was 10% (negative). Hence, it was concluded that CDCXM positivity was secondary to IgM antibodies. To confirm the same, FCXM was performed using FACSCanto™ cytometer.

T- and B-lymphocytes were phycoerythrin stained and were conjugated with mouse monoclonal antibodies specific for human CD3 and CD19, respectively. FCXM was negative.

LUMINEXX platform (LAB screen, One Lambda, Inc. Canoga Park, CA) was used to measure donor-specific antibodies. DSA was found to be negative.

The patient was induced with rabbit antithymocyte globulin (1.5 mg/kg) and she had also received three doses of methylprednisolone 500 mg each.

Maintenance immunosuppression comprised prednisolone 20 mg OD, tacrolimus (0.05 mg/kg) in two divided doses, and mycophenolic acid sodium salt 360 mg QID.

On the day of transplant, the patient achieved urine output of approximately 11 L. The patient's serum creatinine level on postoperative day (POD) 2 was 0.7 mg/dl. Central venous access and drains were removed on POD 3 and per urethral catheter was removed on POD 5. The patient's graft Doppler study was performed on immediate PO period and then on POD 3 which was normal with average resistive index (RI) of 0.6.

Trough tacrolimus level was performed on POD 4 using the immunoassay method which was 9.72 ng/ml. The patient was discharged in stable condition on POD 7.


  Discussion Top


A CDCXM detects both IgG and/or IgM complement fixing antibodies.[4] AHG-CDCXM is more sensitive and can detect antibodies in low titers, but it is less sensitive than FCXM and DSA.[5] Treating recipient serum with DTT, that is, DTT excludes IgM antibodies, which are considered to be innocent in transplant immunology.

FCXM uses IgG-FITC label and hence it cannot detect IgM antibodies.[6] FCXM can therefore detect both complements fixing as well as complement nonfixing IgG antibodies even when they are present in low titers. Therefore, a positive CDCXM with negative FCXM suggests the presence of IgM antibodies and absence of IgG antibodies, that is, AHG-CDCXM positive, DTT-CDCXM negative, and FCXM negative.

Luminex DSA using single antigen beads is considered most sensitive and can detect both IgG and IgM donor-specific antibodies either complement fixing or complement nonfixing.[7]

In our case, it were the autoantibodies which were responsible for the CDCXM false positivity which could be identified only with more sensitive means of crossmatch examination such as FCXM and DSA.


  Conclusion Top


All the three modalities, that is, CDCXM, FCXM, and DSA are important to assess an individual's immunological risk and interpreting all test results in a comprehensive manner can help identify false-positive and false-negative test results.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Graff RJ, Xiao H, Duffy B, Schnitzler MA, Axelrod D, Lentine KL, et al. Transplantation with positive complement-dependent microcytotoxicity crossmatch in contemporary kidney transplantation: Practice patterns and associated outcomes. Saudi J Kidney Dis Transpl 2012;23:234-45.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med 1969;280:735-9.  Back to cited text no. 2
    
3.
Terasaki PI, Mcclelland JD. Microdroplet assay of human serum cytotoxins. Nature 1964;204:998-1000.  Back to cited text no. 3
    
4.
Amos DB, Bashir H, Boyle W, MacQueen M, Tiilikainen A. A simple micro cytotoxicity test. Transplantation 1969;7:220-3.  Back to cited text no. 4
    
5.
Johnson AH, Rossen RD, Butler WT. Detection of alloantibodies using a sensitive antiglobulin microcytotoxicity test: Identification of low levels of pre-formed antibodies in accelerated allograft rejection. Tissue Antigens 1972;2:215-26.  Back to cited text no. 5
    
6.
Garovoy MR, Rheinschmidt MA, Bigos M, Steven K, Thomas E, Krista E, et al. Flow cytometry analysis: A high technology cross match technique facilitating transplantation. Transplant Proc 1983;15:1939-44.  Back to cited text no. 6
    
7.
Pei R, Lee JH, Shih NJ, Chen M, Terasaki PI. Single human leukocyte antigen flow cytometry beads for accurate identification of human leukocyte antigen antibody specificities. Transplantation 2003;75:43-9.  Back to cited text no. 7
    




 

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