Misleading de novo detection of serum anti–HLA-A3 antibodies in kidney recipients having received ATG before transplantation

Masson, Emeline; Devillard, Nadège; Chabod, Jacqueline; Yannaraki, Maria; Thevenin, Chantal; Tiberghien, Pierre; Rebibou, Jean-Michel

doi:10.1016/j.humimm.2009.11.003

Cited by 11 publications

(6 citation statements)

References 23 publications

(28 reference statements)

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“…No information is given about against which class (I and/or II) were the detected anti-HLA antibodies. The main issue here is if this association results from a laboratory interference of a xeno-antibody present in ATG preparation [13] with no foreseeable effect on the graft or if it results from an imbalance between T- and B-cell populations with a stronger depletion effect in the former (including regulatory T-cells) allowing for humoral responses to evolve [14]. Our results are in accordance with the first proposition, since we reported only 2 graft losses in the ATG induced group and no significant difference was detected in acute rejection between patients with and without ATG induction.…”

Section: Discussionmentioning

confidence: 99%

Posttransplant Allosensitization in Low Immunological Risk Kidney and Kidney-Pancreas Graft Recipients

Malheiro

Tafulo

Dias

et al. 2014

BioMed Research International

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Introduction. Posttransplantation allosensitization prevalence and effect on kidney grafts outcomes remain unsettled. Methods. Between 2007 and 2012, 408 patients received a primary kidney graft (with 68 patients also receiving a pancreas graft) after a negative cytotoxic crossmatch. All patients had a pretransplant negative anti-HLA screening and 0% panel reactive antibodies. We analyzed retrospectively the results of anti-HLA antibodies screening by Luminex assay, performed between 6 and 24 months after transplant, and searched for the risk factors for antibody positivity and its impact on kidney graft outcomes. Results. Anti-HLA antibodies prevalence at 6 months was 17.4%. Previous steroid-insensitive acute rejection was the only risk factor for both anti-HLA classes detected antibodies. Antithymocyte globulin induction was also a risk factor for anti-HLA-I antibodies. Antibody positivity status was associated with reduced graft function at 12 months and graft survival at 5 years (91.5% versus 96.4%, P = 0.03). In multivariable Cox analysis, delayed graft function (HR = 6.1, P < 0.01), HLA mismatches >3 (HR = 10.2, P = 0.03), and antibody positivity for anti-HLA class II (HR = 5.1, P = 0.04) or class I/II (HR = 13.8, P < 0.01) were independent predictors of graft loss. Conclusions. Allosensitization against HLA class II ± I after transplant was associated with adverse kidney graft outcomes. A screening protocol seems advisable within the first year in low immunological risk patients.

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Section: Discussionmentioning

confidence: 99%

Posttransplant Allosensitization in Low Immunological Risk Kidney and Kidney-Pancreas Graft Recipients

Malheiro

Tafulo

Dias

et al. 2014

BioMed Research International

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“…Since Thymoglobuline is produced by immunization with human thymocytes of several individuals, multiple HLA class I and II specificities can be present. In the case of Gravalon (immunization with a single Jurkat cell line expressing HLA‐A3, A32, B7, B35), the specificities are better defined, and thus, false‐positive results are easier to identify . In addition, these rabbit HLA antibodies compete with human HLA antibodies for binding to the SAB and can therefore diminish the MFI signal.…”

Section: Technical Challenges and Limitationsmentioning

confidence: 99%

Caveats of HLA antibody detection by solid‐phase assays

2019

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All authors contributed equally to the review SUMMARY Solid-phase assays for human leukocyte antigens (HLA) antibody detection have clearly revolutionized the field of HLA diagnostics and transplantation. The key advantages are a high sensitivity and specificity for detection of HLA antibodies compared with cell-based assays, as well as the potential for standardization. Solid-phase assays enabled the broad introduction of tools such as "virtual crossmatching" and "calculated panel reactive antibodies," which are essential components in many organ allocation systems, kidney-paired donation programs, and center-specific immunological risk stratification procedures. The most advanced solid-phase assays are the socalled single antigen beads (SAB). They are available now for more than 15 years, and the transplant community embraced their significant advantages. However, SAB analysis and interpretation is complex and many pitfalls have to be considered. In this review, we will discuss problems, limitations, and challenges using SAB. Furthermore, we express our wishes for improvements of SAB as well as their future use for immunological assessment and research purposes.

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“…Such ATG antibodies are more likely to bind to host cells and tissues and therefore should not act like DSA. However, evidence for ATG antibodies that specifically react with a certain HLA type has been reported, and this phenomenon certainly merits further investigation . In a previous study, we have found a high homogeneity between different batches of thymoglobulin .…”

mentioning

confidence: 67%

HLA Antibodies in ATGs

Popow

Schmitz

2014

American Journal of Transplantation

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For a long time anti-thymocyte globulins (ATGs) have been known to contain HLA-specific antibodies. We have measured high amounts of HLA Class I antibodies in both ATG preparations, whereas significant HLA Class II antibodies were only found in thymoglobulin (1). Focosi and Boggi (2) speculated that antibodies in ATGs specific for HLA Class I and II antigens might include donor-specific antibodies (DSA) that could be involved in the development of antibody-mediated allograft rejection. However, we presume that most HLA-reactive antibodies contained in ATGs will bind to epitopes shared between different HLA molecules. In our recent study, we have used cells expressing antigens known to be bound by ATGs to deplete both ATG preparations from all identified humanspecific antibodies to prevent the isolation of already known antigens during our screening for new ATG antigens. To deplete ATGs of HLA antibodies, we have used cells expressing only one subtype of HLA-A, -B and -C antigen. This treatment effectively prevented the isolation of cells expressing HLA molecules, which might indicate that most HLA antibodies in ATGs are broadly crossreactive. Such ATG antibodies are more likely to bind to host cells and tissues and therefore should not act like DSA. However, evidence for ATG antibodies that specifically react with a certain HLA type has been reported, and this phenomenon certainly merits further investigation (3). In a previous study, we have found a high homogeneity between different batches of thymoglobulin (4). However, we have not specifically addressed whether different lots differ in their HLA-antibody profile as suggested by Focosi and Boggi (2). This could be effectively investigated by modifying bead-based HLA-antibody assays for the detection of rabbit antibodies. In addition, the use of anti-human immunoglobulin reagents that do not cross-react with antibodies from rabbits or other animals would prevent false positive results in human panel reactive antibody testing without the need for removal of xenogenic antibodies.Recently, it has been shown that CD107a not only is a marker for cytotoxic activity but also prevents cytotoxic cells from self-destruction (5). We agree that it would be interesting to investigate whether ATG interferes with such a protective role of CD107a, thereby suppressing graftspecific lymphocytes.

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Misleading de novo detection of serum anti–HLA-A3 antibodies in kidney recipients having received ATG before transplantation

Cited by 11 publications

References 23 publications

Posttransplant Allosensitization in Low Immunological Risk Kidney and Kidney-Pancreas Graft Recipients

Posttransplant Allosensitization in Low Immunological Risk Kidney and Kidney-Pancreas Graft Recipients

Caveats of HLA antibody detection by solid‐phase assays

HLA Antibodies in ATGs

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