| Assay Type | Agreement with ID | Predictive Value for FVC Decline |
|---|---|---|
| Immunodiffusion (ID) | Reference | |
| CIA | κ = 0.66 | (NS) |
| LIA | κ = 0.568 | (NS) |
Implication: ID remains critical for patient stratification in trials targeting ILD progression. CIA/LIA may require cutoff recalibration to improve prognostic utility .
pH-dependent binding: Engineered to enhance FcRn recycling (plasma half-life >30 days in primates) .
Surface charge modulation: Reduced isoelectric point (pI) accelerates immune complex clearance, minimizing C5 accumulation () .
COSMO mutagenesis: 1,000+ variants screened via high-throughput PCR transfection for binding optimization .
Technical challenge: Balance between improving pharmacokinetics and avoiding immunogenicity requires iterative humanization and in silico epitope analysis .
Antigen source: ID uses native calf thymus topoisomerase I, while CIA/LIA employ recombinant or peptide antigens lacking post-translational modifications .
Cutoff variability: CIA/LIA thresholds (e.g., 20 U/mL vs. 40 U/mL) may exclude patients with low-titer, clinically significant antibodies .
Resolution: Standardize antigen sources across assays and validate against clinical endpoints (e.g., FVC decline ≥10%/year).