Abstract
Background: Serum free light chains (sFLCs) are established markers of monoclonal plasma cell disease, but polyclonal elevations are increasingly recognised as a readout of B-cell activation, systemic inflammation and reduced renal clearance. Data on how polyclonal sFLCs behave across the mixed case-mix of a general hospital laboratory remain limited. Objective: To describe serum kappa (κ), lambda (λ) and the κ/λ ratio in adults tested for chronic viral infection, glycaemic control and myocardial injury, and to examine their correlation with the corresponding serological, metabolic, renal and cardiac markers. Methods: Cross-sectional study conducted in the central laboratory of a tertiary care teaching hospital. Adults aged 18 years or above in whom a serum free light chain assay had been requested were eligible; 300 participants were analysed (chronic viral infection 88, dysglycaemia 71, suspected myocardial injury 54, comparison group 87). Patients with known plasma cell dyscrasia, estimated glomerular filtration rate below 60 mL/min/1.73 m², or systemic autoimmune disease were excluded. Kappa and lambda free light chains were quantified by immunoassay. Correlation analyses were restricted to participants in whom the comparator analyte had been measured on the same sample as the free light chain assay, so the number of pairs varies by analyte (n = 15 to 87). Associations were tested with Spearman rank correlation, with two-tailed p < 0.05 taken as significant. Results: Serum κ and λ correlated positively with serum creatinine (ρ = 0.324, p = 0.0028 and ρ = 0.318, p = 0.0034; n = 83), and this was the most consistent association observed. Anti-HCV reactivity showed weak positive correlations with κ (ρ = 0.212, p = 0.0486) and λ (ρ = 0.246, p = 0.0216; n = 87). HbA1c correlated with the κ/λ ratio (ρ = 0.459, p = 0.0275; n = 23) but not with either chain individually. No significant correlation was demonstrated between sFLC measures and HIV status (n = 34), CK-MB (n = 22) or troponin I (n = 15). The κ/λ ratio lay within the reference interval in 279 of 300 participants (93.0%). Conclusion: In this hospitalbased cross-sectional sample, polyclonal sFLC concentrations tracked renal function more closely than any infective, metabolic or cardiac marker. Weak associations with anti-HCV reactivity and with HbA1c were observed but require confirmation in adequately powered samples. Serum free light chains should be interpreted alongside renal function before being attributed to immune activation.
Keywords: Free light chains; Polyclonal B-cell activation; Hepatitis C; HbA1c; Creatinine