Role of serum CXCL9 and CXCL13 in predicting infection after kidney transplant

Abstract

Chemokines are majorly involved in inflammatory and immune responses. The interferon-γ-inducible chemokines C-X-C motif chemokines 9 and 10 (CXCL9 and CXCL10) are considerably associated with Th1 cells and monocytes, and their expression levels rapidly increase during the early episodes of renal allograft rejection and various infectious diseases. CXCL13 is one of the most potent B-cell and T follicular helper-cell chemoattractants. The expression of CXCL13 in the presence of infection indicates an important chemotactic activity in multiple infectious diseases. C-C motif chemokine ligand 2 (CCL2) can attract monocytes and macrophages during inflammatory responses. However, there are no studies on the role of these chemokines in posttransplant infection in kidney transplant recipients. In this study, CXCL9, CXCL10, CXCL13, and CCL2 were analyzed using the Bio-Plex suspension array system before transplant and 30 days after transplant. The serum levels of CXCL9 and CXCL13 30 days after kidney transplant were associated with infection within 1 year after transplant (P = .021 and P = .002, respectively). The serum levels of CXCL9 and CXCL13 before surgery and those of CCL2 and CXCL10 before and after surgery were not associated with infection within 1 year after transplant (P > .05). The combination of postoperative day (POD) 30 CXCL9 and postoperative day 30 CXCL13 provided the best results with an area under the curve of 0.721 (95% confidence interval, 0.591–0.852), with a sensitivity of 71.4% and specificity of 68.5% at the optimal cutoff value of 52.72 pg/mL. As important chemokines, CXCL9 and CXCL13 could be used to predict the occurrence of infection after kidney transplant.

CXCL13 Is an Indicator of Germinal Center Activity and Alloantibody Formation Following Transplantation

“…20,21 Although the relationship between CXCL13 and the development of DSA in transplantation has not been previously reported, some preliminary studies have described an association between CXCL13 and posttransplant status in heart recipients, as well as chronic allograft dysfunction in renal transplant patients. 22,31 More relevant to humoral alloresponses, elevated tissue and urinary CXCL13 levels have been observed to correlate with B-cell infiltrates and renal dysfunction in cases of T-cell and antibody-mediated rejection, respectively. 23,24 In humans, CXCL13 has also been associated with active chronic graft-versus-host disease, 32 a disease process that has been demonstrated to depend on GC formation and alloantibodies.…”

“…Preliminary data on CXCL13 postkidney transplant have linked it with the occurrence of infections in 1 study, and increased levels have also been associated with ischemia reperfusion injury and autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus. 20,31,34 Although random banked serum samples from stable recipients and those with de novo DSA were used for the cross-sectional analysis of CXCL13 between the groups (Figure 3A), prospective validation studies will be needed to build on these preliminary data and better evaluate the utility and specificity of CXCL13 as a potential biomarker of DSA in larger, more heterogenous transplant populations.…”