Antibody Detection & Characterization Flashcards

Non-HLA antibodies have been implicated in transplant rejection. Which non-HLA target is most studied?

Answer: MICA (MHC class I chain-related antigen A)

MICA is a stress-induced cell surface molecule encoded in the MHC region; anti-MICA antibodies have been associated with rejection and graft loss independent of HLA.

Which immunoglobulin subclass of IgG most efficiently activates complement and is most associated with acute AMR?

Answer: IgG1 and IgG3

IgG1 and IgG3 are the most potent complement-activating IgG subclasses and are strongly associated with antibody-mediated rejection.

What does it mean when DSA is described as 'complement-binding' in the clinical context?

Answer: The antibody can activate the classical complement cascade, increasing rejection risk

Complement-binding DSA (e.g., C1q-binding or C3d-fixing) indicates the antibody can activate complement, which is associated with more severe AMR and worse graft outcomes.

In Luminex-based crossmatch (LCM/FCXM by bead), what advantage does it have over traditional CDC crossmatch?

Answer: Higher sensitivity for detecting low-level HLA antibodies

Luminex and flow cytometric crossmatches are significantly more sensitive than CDC, detecting antibody levels too low to activate complement but still potentially harmful.

What is the purpose of DTT (dithiothreitol) treatment of serum in HLA antibody testing?

Answer: Inactivates IgM antibodies by breaking disulfide bonds to allow IgG-only testing

DTT cleaves the disulfide bonds that hold IgM pentamers together, inactivating IgM antibodies so the assay result reflects only IgG antibodies.

Which type of HLA antibody specificity is considered most critical to identify before transplantation?

Answer: Donor-specific antibodies (DSA) directed against the specific donor's HLA antigens

DSA against the specific donor's HLA antigens are the most clinically critical to identify, as they predict positive crossmatches and risk for hyperacute and AMR.