High pretransplant serum levels of CXCL9 are associated with increased risk of acute rejection and graft failure in kidney graft recipients.
Several clinical and experimental models have underlined the role of the CXCR3-binding chemokines in the immune-mediated kidney diseases. This study aimed to investigate the predictive value of measuring pretransplant CXCL9 levels for acute rejection (AR) onset and kidney transplantation outcome. Pretransplantation serum levels of CXCL9 were tested retrospectively in 252 kidney graft recipients, whose stratification in two groups according to CXCL9 levels (<272.1 pg/ml vs. >272.1 pg/ml) showed highly significant differences in 5-year survival rates (97.7% vs. 73.3%; P < 0.001). Multivariate analysis demonstrated that among the analysed variables, CXCL9 [relative risk (RR) 11.708] and AR (RR 3.604) had the highest predictive power of graft loss. Accordingly, patients with AR (254.4 + or - 22.1; P < 0.05) and, even more, those with anti-thymoglobulin (ATG)-treated AR also showed increased pretransplant serum CXCL9 levels (319.3 + or - 28.1, P < 0.001). Moreover, CXCL9 expression and distribution were investigated in tissue specimens obtained from 10 patients affected by AR, and wide CXCL9 expression was detected not only in infiltrating inflammatory cells but also in vascular and tubular structures. Measurement of pretransplant serum CXCL9 levels might represent the tracking of a clinically useful parameter to identify subjects at high risk of AR and graft failure. These findings might be used for the individualization of immunosuppressive therapies.
Rotondi
Mario
M
Excellence Center for Research, Transfer and High Education DENOthe, University of Florence, Florence, Italy. mario.rotondi@fsm.it
Netti
Giuseppe Stefano
GS
Lazzeri
Elena
E
Stallone
Giovanni
G
Bertoni
Elisabetta
E
Chiovato
Luca
L
Grandaliano
Giuseppe
G
Gesualdo
Loreto
L
Salvadori
Maurizio
M
Schena
Francesco Paolo
FP
Romagnani
Paola
P
Serio
Mario
M
D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000961:Antilymphocyte Serum; D054370:Chemokine CXCL9 / Q000097:blood*; D005260:Female; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D057234:Preoperative Period; D012306:Risk; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D007166:Immunosuppressive Agents; C512542:thymoglobulin