Population-specific antiphospholipid antibody titres in a South Indian cohort: defining cut-off values and implications for diagnosis from a cross-sectional validation study

Significant titers of antiphospholipid antibodies (aPL) vary across populations, but the clinically relevant threshold for diagnosing antiphospholipid syndrome (APS) in South Indians is unknown. This study aimed to determine population-specific aPL cut-off values in South India. We conducted a cross-sectional validity study at a tertiary care hospital in Kerala, India. Blood samples from 125 healthy individuals were analyzed to establish cut-off values for anticardiolipin (aCL) and anti-beta-2-glycoprotein I (anti-β2GPI) antibodies (IgG/IgM) using ELISA. Cut-off values were calculated using both 95th and 99th percentile methods (before and after excluding outliers) and receiver operating characteristic (ROC) curve analysis. Validity was evaluated by comparing 118 patients with APS criteria manifestations to 81 patients without such manifestations. aPL values showed a non-parametric distribution. The 99th percentile cut-offs before excluding outliers were 17.3 GPL (IgG aCL), 12.4 MPL (IgM aCL), 41.5 SGU (IgG anti-β2GPI), and 23.4 SMU (IgM anti-β2GPI). After excluding outliers, 99th percentile values were 2.6 GPL, 12.4 MPL, 16.7 SGU, and 15.7 SMU, respectively. The 99th percentile cut-offs had superior specificity when outliers were not excluded, while ROC-derived cutoff values yielded a greater Youden Index compared to the other cutoff’s, in all aPLs. This is the first study to define aPL reference values for South Indians, revealing substantial differences from manufacturer recommendations, Modified Sapporo criteria, and international data. Region-specific aPL thresholds are essential for accurate APS diagnosis. Standardizing cut-off calculation methods is recommended to improve diagnostic accuracy and interpretation across populations.