Serum Concentrations of Polyclonal Free Light Chains Predict Post Transplantation Infections

Abstract

Polyclonal immunoglobulin (Ig) free light chains (FLC) represent the activity of the adaptive immune system. However unlike intact Ig, FLCs are principally cleared by the kidneys and have short serum half lives. Previous work has demonstrated that serum FLC concentrations are influenced by the dose of immunosuppressants used post transplantation. The purpose of this study was to determine if polyclonal FLC concentrations predict the future risk of infective episodes in renal transplant recipients. Methods: Serial serum samples collected from 79 incident renal transplant recipients were assessed for FLCs, Ig and cystatin C concentrations. Combined polyclonal FLC (cFLC) concentration was calculated by summating k+l. A correction for renal function was then made with cystatin C ([k+l]/cysC). Clinical data was captured prospectively. Statistical significance was assessed using Kruskall-Wallace with Dunn's post-test and Pearson's Chi-square test. Results: By day 14 post-transplant, the median eGFR was 47.50ml/min this remained stable at 12 months (median 47ml/min, range 7-90). Median serum cFLC pre-transplant was increased at 145.9mg/L (range 21.27-442.5mg/L; normal range 9.33-44.27mg/L). cFLC was significantly reduced by day 14 median 25.67mg/L, p< 0.001, and remained reduced at 12 months (median 30.64mg/L, p< 0.001). Baseline corrFLC was 28.7mg/L (range 12.7-77.3mg/L) these decreased to 13.7mg/L, p< 0.001 by day 14, but then steadily increased over the follow up period (p< 0.001). A similar pattern was observed with IgG (baseline vs. day 14 p< 0.001, 1 month vs. 12 months p< 0.05). Sixty of the 79 patients (76%) experienced at least one infective episode during the first 12 months post transplantation. Patients with a low corrFLC level were more likely to experience an infection in the 90 days following the sample (78%) than patients within or above the normal range (43%) (p=0.002). Increases in corrFLC concentrations mirrored infective episodes. There was no difference in FLC concentrations between patients who received an ABO incompatible kidney (19/79 patients). Conclusion: Serum concentrations of polyclonal FLCs represent a dynamic marker of immune activity and can be used to identify patients at higher risk of infective episodes post transplantation. Future work is now required to determine if the doses of immunosuppressants can be modified ‘real-time’ in relationship to the cFLC levels.