Elevated B-Cell Autoantibodies Among HIV+ Transplant Candidates: Crossmatch Implications

Kimball, Pamela; Wagner, B.

doi:10.1016/j.transproceed.2005.10.051

Cited by 3 publications

(4 citation statements)

References 21 publications

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“…The T-cell CDC-XM was negative in all HIV-positive and HIV-negative individuals. 25 In contrast, the proportions of positive B-cell CDC crossmatches and FC crossmatches were higher in HIV-positive individuals than in HIVnegative individuals (71% vs 4% for CDC-XM and 45% vs 2% for FC-XM). Moreover, the proportion of positive FC-XMs was greater in patients with detectable circulating HIV RNA (57%) than in those without (25%).…”

Section: Human Immunodeficiency Virus-positive Casesmentioning

confidence: 88%

“…This strongly suggested that FC-XM reactivity was due to specific autoantibodies recognizing cryptic epitopes exposed by the pronase treatment of T cells. 25,26 Interference by therapeutic antibodies and other treatments The therapeutic antibodies used to treat acute rejection or to desensitize patients (such as rituximab [an anti-CD20 antibody], daclizumab [anti-CD25], and alemtuzumab [anti-CD52]) can interfere with crossmatching assays. 27 In a recent study, CDC-XM was performed after the addition of various concentrations of therapeutic antibodies (intravenous immunoglobulins, rituximab, basiliximab, eculizumab, and antithymocyte globulin) to negative and positive control sera.…”

Section: Human Immunodeficiency Virus-positive Casesmentioning

confidence: 99%

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Desoutter

Apithy²,

Guillaume³

2017

Exp Clin Transplant

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Preformed donor-specific antibodies against human leukocyte antigen can induce antibody-mediated rejection after organ transplant. Hence, future transplant recipients undergo pretransplant screening for preformed antibodies (ie, virtual crossmatch). Subsequently, prospective (analytic) crossmatching is performed using conventional, complementdependent cytotoxicity assays and/or flow cytometrybased methods. The present article reviews factors that must be considered when unexpected, positive, prospective crossmatches are observed. First, the prozone effect caused by the interference of complement or immunoglobulin M must be abrogated by treating the serum with moderate heat, dilution, hypotonic dialysis, EDTA, or dithiothreitol. Second, the physician must check for the presence of potentially interfering autoantibodies (in a context of autoimmune disease or human immunodeficiency virus infection) or therapeutic antibodies (such as rituximab and antithymocyte globulin). In conclusion, knowledge of each assay's technical characteristics will enable the physician to reliably interpret any discrepancies. The reasons for an unexpected, positive, prospective crossmatch must be elucidated before transplant to ensure efficient organ allocation and optimize patient outcomes.

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Section: Human Immunodeficiency Virus-positive Casesmentioning

confidence: 88%

Section: Human Immunodeficiency Virus-positive Casesmentioning

confidence: 99%

Untitled

Desoutter

Apithy²,

Guillaume³

2017

Exp Clin Transplant

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“…Pronase treatment of donor cells is thought to enhance the specificity of FC‐XM. However, some limitations of pronase treatment have been reported in the literature, such as false negative results due to a reduction of MHC expression on lymphoid cells, and false positive T‐cell FC‐XM results as example in HIV‐positive patients due to the exposure of cryptic epitopes . We studied the impact of treatment with a range of pronase concentrations (from 0 to 3 mg/mL) on CD3, CD19, CD20, kappa light chain, and MHC‐I and ‐II expression.…”

Section: Discussionmentioning

confidence: 99%

“…However, some limitations of pronase treatment have been reported in the literature, such as false negative results due to a reduction of MHC expression on lymphoid cells, and false positive T-cell FC-XM results as example in HIV-positive patients due to the exposure of cryptic epitopes. 9,[12][13][14] We studied the impact of treatment with a range of pronase concentrations (from 0 to 3 mg/mL) on CD3, CD19, CD20, kappa light chain, and MHC-I and -II expression. Treatment pronase (1 mg/mL for 30 minutes at 37 C) had a moderate (and therefore acceptable) impact on MHC expression and our ability to interpret the FC-XM results.…”

Section: Discussionmentioning

confidence: 99%

Pronase treatment improves flow cytometry crossmatching results

Apithy

Desoutter

Gicquel

et al. 2017

HLA

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Flow cytometry crossmatching (FC-XM) is the most sensitive cell-based method for detecting donor-specific antibodies in clinical organ transplantation. Unfortunately, background FC-XM reactivity is elevated in assays with B lymphocytes-partly because of nonspecific immunoglobulin binding by Fc receptors and B-cell surface immunoglobulins. To reduce the background reactivity in a B-cell FC-XM assay, we treated lymphocytes with pronase (1 mg/mL for 30 minutes). This treatment drastically reduced the presence of kappa light chains and Fc receptors (CD32b), while the concomitant decrease in CD19, CD20 and major histocompatibility complex (MHC) I and II expression on B-cells was acceptable. Higher pronase concentrations (>2 mg/mL) started to significantly affect CD19, CD20, MHC-I and -II expression on B-cells. In subsequent prospective experiments (on 42 donor cells tested with 102 sera), we found that pronase treatment was associated with a relative increase of the sensitivity and specificity in our B-cell FC-XM assay.

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Patients with immunological diseases or on peritoneal dialysis are prone to false positive flow cytometry crossmatch

House

Leckie

et al. 2019

Human Immunology

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Elevated B-Cell Autoantibodies Among HIV+ Transplant Candidates: Crossmatch Implications

Cited by 3 publications

References 21 publications

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Untitled

Pronase treatment improves flow cytometry crossmatching results

Patients with immunological diseases or on peritoneal dialysis are prone to false positive flow cytometry crossmatch

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