FLA2 Antibody

Definition and Target Antigen

FLA2 antibody refers to immunoglobulin G (IgG) or IgA antibodies directed against A4-Fla2, a bacterial flagellin protein. Flagellins are structural components of bacterial flagella, and A4-Fla2 is associated with immune responses in CD patients .

Discovery and Development

• Identification: A4-Fla2 was identified as a microbial antigen triggering antibody responses in CD patients during studies comparing serological profiles across inflammatory bowel disease (IBD) subtypes .

• Assay Validation: ELISA protocols were standardized using cohorts of CD, ulcerative colitis (UC), and healthy controls. Plates coated with 1 μg/mL A4-Fla2 detected antibodies at 1:1000 serum dilution .

Association with Disease Phenotypes

• Stricturing Behavior: Anti-A4-Fla2 antibodies correlate with stricturing (narrowing) intestinal lesions (OR = 1.8, P = 0.027) .

• Small Bowel Involvement: Linked to ileal or ileocolonic disease localization (P = 0.013) .

• Disease Activity: Elevated IgG levels associate with active CD (IRR = 1.64, P = 0.0238), though significance diminishes after adjustment .

Prevalence

Diagnostic Utility

• Sensitivity/Specificity: 47% sensitivity and 96% specificity for CD diagnosis .

• Comparative Performance: Outperforms ASCA (37–72% sensitivity) and p-ANCA (50–71% sensitivity in UC) in specificity .

Mechanistic Insights

• Pathogenic Role: Antibodies to A4-Fla2 reflect systemic immune reactivity to gut microbiota, potentially exacerbating inflammation via Th1-mediated pathways .

• Genetic Links: Co-occurs with NOD2 mutations (associated with ileal CD) in 7% of CD patients .

Comparative Analysis with Other IBD Markers

Limitations and Future Directions

• Non-Causal Role: Antibody presence does not confirm microbial causality .

• Therapeutic Potential: Unclear if targeting A4-Fla2 modulates disease progression.