CXCL13 as a Novel Marker for Diagnosis and Disease Monitoring in Pediatric PTLD

Abstract

Posttransplant lymphoproliferative disease (PTLD) is a severe complication of immunosuppressive treatment in organ-grafted children. Early diagnosis of PTLD is hampered by both unspecific clinical symptoms and lack of easy accessible markers. The homeostatic chemokine CXCL13, which plays a crucial role in Bcell homing and lymphoid organ development, is expressed in some lymphomatous diseases. This study aims to investigate whether serum CXCL13 (sCXCL13) levels correlate with occurrence and regression of PTLD in pediatric solid-organ graft recipients. Serum samples from PTLD patients (n = 21), patients with Epstein-Barr virus (EBV) reactivation (n = 18), and healthy age-matched controls (n = 19) were tested for CXCL13 using a commercially available ELISA kit. sCXCL13 levels were significantly higher in PTLD patients than in healthy children. PTLD patients had also higher sCXCL13 values than pediatric solid-organ recipients with EBV reactivation. An increase in sCXCL13 levels was observed from EBV reactivation to PTLD diagnosis in most cases. Elevated sCXCL13 levels were detected up to 2 years prior to PTLD diagnosis and correlated well with response to cytoreductive treatment in individual patients. sCXCL13, thus, may be a readily available surrogate marker for the diagnosis of PTLD and for monitoring of response to treatment in patients with initially elevated sCXCL13 levels.

How I treat posttransplant lymphoproliferative disorders

“…[88][89][90] Other potential candidates allowing preventive or prophylactic interventions include measurements of interleukin-6, interleukin-10, and chemokine (C-X-C motif) ligand 13. [91][92][93] However, these approaches have not yet been validated in larger series.…”

Posttransplant Lymphoproliferative Disease after Pediatric Solid Organ Transplantation

“…Increased levels of inflammatory proteins like IL-6 or IL-10 were documented in PTLD patients [114], but they were either unspecific (IL-6) or did not correlate with the course of the disease (IL-10). Our group has recently identified CXCL13, a homeostatic B-cell chemokine, to be elevated in serum of patients with PTLD [115]. In anecdotal cases elevation of CXCL13 preceded the development of PTLD by several months; however, the sensitivity and specificity of serum CXCL13 as high PTLD risk marker needs to be confirmed in a prospective patient cohort.…”

“…Techniques quantifying metabolic activity of morphologic lesions (e.g., 18 FDG-PET scan) may prove useful to individually tailor treatment in patients with residual lesions [116] similar to developing strategies in nonimmunocompromised individuals. While EBV load monitoring did not correlate with treatment response in a small adult series, longitudinal monitoring of serological markers like IL-6 [114] or CXCL13 [115] may allow for early identification of treatment failures. …”

Posttransplant Lymphoproliferative Disorder in Pediatric Patients

“…Frozen or formalin-fixed and paraffin-embedded tissues can be used for PCR analysis of clonality and/or fluorescence in situ hybridization, in particular for the evaluation of rearrangements of 8q24, the gene locus of MYC. Serological markers, such as increasing EBV load [26,27] or chemokine (C-X-C motif) ligand 13 (CXCL13) [28] and positron emission tomography with [18F]-2-fluoro-2-desoxy-glucose [29] may facilitate discrimination between PTLD and other posttransplant complications, but these methods have a much lower specificity and sensitivity than histology and are therefore not applicable for primary diagnostics. Furthermore, serological markers are mainly analyzed in extracranial PTLD, although cerebral manifestation can be associated with no detectable EBV in the peripheral blood but EBV positivity in the liquor [30,31].…”