Comparison Between Total IgG, C1q, and C3d Single Antigen Bead Assays in Detecting Class I Complement-Binding...

Area of Science:

• Transplant immunology
• Immunochemistry
• Serology

Background:

• Complement-binding donor-specific antibodies (DSAs) are linked to antibody-mediated rejection and graft loss.
• Novel complement component 1q (C1q) and complement component 3d (C3d) single antigen bead (SAB) assays detect complement-binding DSAs.
• The comparative efficacy of these novel assays versus total IgG SAB assays for detecting complement-binding DSAs is not well-established.

Purpose of the Study:

• To compare the diagnostic capabilities of total IgG, C1q, and C3d SAB assays.
• To determine the sensitivity of different SAB assays in detecting complement-binding anti-human leukocyte antigen (HLA) antibodies.

Main Methods:

• Twenty sera with known complement-binding anti-HLA antibodies were analyzed.
• Three SAB assays were employed: total IgG (undiluted and 1:8 dilution), C1q, and C3d.
• Serologic anti-HLA specificities were compared across the different SAB assay results.

Main Results:

• Total IgG SAB assays demonstrated higher sensitivity in detecting complement-binding antibodies (24/24, 100% sensitivity).
• Pearson correlation revealed a significant association between C1q and IgG SAB assays (r=0.347, P<0.0001) at specific cutoffs.
• No significant association was found between C3d and IgG SAB assays (r=-0.173, P=0.279) at specified cutoffs.

Conclusions:

• For detecting complement-binding class I anti-HLA antibodies, total IgG SAB assays with a high mean fluorescence intensity (MFI) cutoff (>5000) are more sensitive than C1q and C3d SAB assays.
• These findings suggest that total IgG SAB assays are currently superior for identifying potentially harmful complement-binding antibodies in transplant recipients.