Serum Free Light Chain Is Not a Good Biomarker to Predict Post-Transplant Lymphoprolipherative Disorder Development in Renal Transplanted Patients

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening Epstein-Barr virus (EBV)-driven B-cell malignancy occurring in 1–4% of renal transplanted patients. EBV DNA quantification has become a useful tool for identifying patients at risk of developing PTLD. However, studies on EBV load differ in source of sample, methodology and patients' characteristics, making it difficult to compare data from different studies. Therefore, other less expensive and more reproducible methods to predict PTLD development are needed. Recently, some studies have shown a correlation between increased levels of serum free light chains (sFLC) and high risk of development of lymphoproliferative diseases in autoimmune disorders, hepatitis C and Acquired Immune Deficiency Syndrome (AIDS). However, none of those studies has assessed the value of sFLC as a predictive biomarker for the development of lymphoproliferative disorders.

The aim of the present study was to determine the predictive value of sFLC quantification for the development of PTLD, using serum samples from a nested case-control cohort of renal transplanted patients and from EBV-positive and negative subjects as comparative groups.

Ten new cases of PTLD after renal transplant were enrolled at University Hospital São Paulo and Hospital do Rim e Hipertensão, Brazil. Forty-six controls (4–5 per case) matched by age, date of transplant, type and dosage of immunosuppression, and history of rejection episodes were selected from the cohort. The diagnosis of PTLD was confirmed histologically by two experienced pathologists and classified using the WHO criteria. The comparison groups consisted of 5 HIV-infected/AIDS individuals with CD4 count less than 100 cells/mm³, 5 recently diagnosed and untreated Hodgkin′s lymphoma patients, 4 normal blood donors and 2 children aged from 6 to 18 months (with EBV-negative serology). The samples were collected and stored at −80°C for 10 to 12 years and all of them were in conditions of use for the current study. In all samples, serum κ and λ FLC concentrations were measured by nephelometry and compared with reference ranges (κ: 0. 33–1. 94 mg/dL; λ: 0. 57–2, 63 mg/dL). However, as cases and controls do not have always “normal” renal function, the ratio between κ and λ was compared with a new reference range for patients with kidney failure (renal range, κ/λ: 0. 37–3. 17), whereas for comparison groups, who have normal renal clearance, the ratio was compared with the normal range (κ/λ: 0. 26–1. 65).

sFLC levels were abnormal (κ and/or λ above the normal range) in 90% of cases and 65% of controls (matched transplanted patients with no PTLD). There was no statistically significant difference between all groups, except for λ FLC concentrations between PTLD cases and normal blood donors and EBV-negative children (p=0. 016). The κ/λ sFLC ratios of cases and controls were within the renal range and even within normal range, i. e., no monoclonal cases were detected by this method using two cut-offs possibilities.

Our results suggest that sFLC is not useful to predict PTLD development in renal transplanted recipients. Therefore, more studies are needed to find a biomarker capable of predicting the development of PTLD in renal transplanted recipients.

No relevant conflicts of interest to declare.