Immunoglobulin (Ig)G purified from human sera mirrors intravenous Ig human leucocyte antigen (HLA) reactivity and recognizes one's own HLA types, but may be masked by Fab complementarity-determining region peptide in the native sera

Ravindranath, Mepur H.; Terasaki, Paul I.; Maehara, Curtis; Jucaud, Vadim; Kawakita, Satoru; Pham, Tho D.; Yamashita, Wataru

doi:10.1111/cei.12450

Cited by 13 publications

(15 citation statements)

References 37 publications

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“…However, the use of IgHPolyFab without validation for immunoassays, particularly for the simultaneous monitoring of several Abs in a Luminex Multiplex SAB assay, will surely produce misleading assessment of Abs (false positivity) in the sera of patients waiting for donor organs. MFIs obtained with IgHPolyFab are a yardstick for clinicians to desensitize the patients by administering immunosuppressive therapies; some of them are cytotoxic to all immune cells (e.g., anti-thymoglobulin Abs) (36), and others contain higher levels of HLA-I and HLA-II Abs (e.g., IVIg or blood transfusion from female donors) (29,30). It is well known that immunosuppressed allograft recipients succumb to infection (37)(38)(39)(40)(41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

“…The IVIg preparations examined earlier (29,30) were used: GamaSTAN S/D (15-18%, Lot 26NHCVI), GAMUNEX-C (10%, Lots 26NKLG1 and 26NKLK1; all from Talecris Biotherapeutics, Research Triangle Park, NC), and Octagam (6%, Lot A913A8431; Octapharma Pharmazeutika, Lachen, Switzerland). All IVIg was serially diluted with 13 PBS (pH 7.2).…”

Section: Sources Of the Therapeutic Preparations Of Ivigmentioning

confidence: 99%

“…HLA-I and HLA-II IgG reactivity were analyzed using SAB, and data were acquired with a dual-laser flow cytometry Luminex-xMAP (LABScanTM 100; One Lambda) (5,(28)(29)(30). The single rHLA-Ia and rHLA-II Ags in LS1A04-Lot 007 (for HLA-Ia) contain 31 HLA-A, 50 HLA-B, and 16 HLA-Cw molecules, whereas those in LS.2 A01009 (Lot 9) (for HLA-II) contain 29 HLA-DRB1, 7 HLA-DRB3,4,5, 29 HLA-DQ, and 26 HLA-DP molecules.…”

Section: Luminex Multiplex Sab Assaymentioning

confidence: 99%

“…Disparity in the number of anti-HLA IgG Abs recognized by the two 2nd-Abs in IVIg. All IVIg preparations showed a wide variety of HLA-I and HLA-II reactivities, with varying MFIs (29,30,35). Table IV reveals the striking disparity in the number of anti-HLA-I and anti-HLA-II Abs recognized by IgHPolyFab and FcMonoIgG in the IVIg preparations.…”

Section: Anti-hla Igg In Therapeutic Preparations Of Ivigmentioning

confidence: 99%

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Nature and Clonality of the Fluoresceinated Secondary Antibody in Luminex Multiplex Bead Assays Are Critical Factors for Reliable Monitoring of Serum HLA Antibody Levels in Patients for Donor Organ Selection, Desensitization Therapy, and Assessment of the Risk for Graft Loss

Ravindranath

Jucaud

Banuelos

et al. 2017

The Journal of Immunology

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Luminex multiplex immunoassays enable simultaneous monitoring of Abs against multiple Ags in autoimmune, inflammatory, and infectious diseases. The assays are used extensively to monitor anti-HLA Abs in transplant patients for donor organ selection, desensitization, and assessing the risk for graft rejection. To monitor IgG Abs, fluoresceinated IgG constant H chain–binding polyclonal F(ab′)2 (IgHPolyFab) is used as the fluoresceinated secondary Ab (2nd-Ab), whereas IgG subclasses are monitored with Fc-specific monoclonal whole IgG (FcMonoIgG). The fluorescent signal from the 2nd-Ab is measured as mean florescence intensity (MFI). When IgHPolyFab is used, the signal is amplified as a result of the binding of multiple polyclonal Fabs to the C region of primary IgH. The reliability of such amplification for Ab measurements was not validated, nor were MFIs compared with 1:1 binding of FcMonoIgG to primary Abs. Comparing the MFIs of anti-HLA Abs obtained with IgHPolyFab and FcMonoIgG against normal human sera, IVIg, and allograft recipients’ sera, it was observed that the number of HLA-Abs was notably higher with IgHPolyFab than with FcMonoIgG. The MFIs of anti-HLA Abs also remained higher with IgHPolyFab in the normal sera and in IVIg, but the reverse was true when the autologous and allogeneic IgG concentrations were augmented in allograft recipients. Indeed, MFIs of the de novo allo-HLA Abs were markedly higher with FcMonoIgG than with IgHPolyFab. Serum titration established the superiority of FcMonoIgG for monitoring MFIs of de novo allo-HLA Abs in allograft recipients. Avoiding false amplifications of the number and MFIs of anti-HLA IgG with FcMonoIgG may minimize immunosuppressive therapies, maximize the number of donors for patients waiting for allografts, and enable better prediction of graft rejection.

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Section: Discussionmentioning

confidence: 99%

Section: Sources Of the Therapeutic Preparations Of Ivigmentioning

confidence: 99%

Section: Luminex Multiplex Sab Assaymentioning

confidence: 99%

Section: Anti-hla Igg In Therapeutic Preparations Of Ivigmentioning

confidence: 99%

See 2 more Smart Citations

Nature and Clonality of the Fluoresceinated Secondary Antibody in Luminex Multiplex Bead Assays Are Critical Factors for Reliable Monitoring of Serum HLA Antibody Levels in Patients for Donor Organ Selection, Desensitization Therapy, and Assessment of the Risk for Graft Loss

Ravindranath

Jucaud

Banuelos

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In addition, the group also observed sHLA-II in the synovial fluid of patients with active rheumatoid arthritis. Later, Westhoff, et al [164] utilizing two mAbs specific for HLA-DR/-DP (mAb Tii35) and HLA-DQ (mAb Tii22) measured sHLA-II molecules -DR, -DQ, -DP. The population analysis of 209 unrelated, HLA-typed healthy donors showed a mean sHLA-II protein concentration of 1.53 + 2.44 mg/ ml in plasma.…”

Section: Soluble Hla-ii In Serummentioning

confidence: 99%