Circulating monocyte chemoattractant protein-1 in heart transplant recipients with cardiac allograft vasculopathy

Beaudeux, Jean Louis; Dorent, Richard; Bernard, Maguy; Reagan, Mary; Foglietti, Marie-José; Gandjbakhch, I; Cacoub, Patrice

doi:10.1016/s0009-9120(02)00276-x

Cited by 5 publications

(3 citation statements)

References 8 publications

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“…This finding further supports the concept that only the production of certain types of chemokines can adequately predict the individual immune response to transplant. Consistently with this observation, serum levels of another CXCR3‐binding chemokine, CXCL11 (45), but not those of CCL2 (46) were found to be increased in patients with transplant coronary vasculopathy. Interestingly, a recent study has shown that ELISPOT measurements of IFN‐γ release by T cells of the recipients during the first 6 months after transplant predict allograft failure (47), underlining the role of the CXCR3/IFN‐γ axis in the immune response to transplant.…”

Section: Discussionsupporting

confidence: 71%

High Pretransplant Serum Levels of CXCL10/IP-10 Are Related to Increased Risk of Renal Allograft Failure

Rotondi¹,

Rosati²,

Buonamano³

et al. 2004

American Journal of Transplantation

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In experimental models, the chemokine CXCL10/IP-10 is required for graft failure owing to both acute and chronic rejection. In the present study, pretransplantation sera from 316 cadaver kidney graft recipients were tested for serum CXCL10 and CCL22/MDC levels by an ELISA assay. Kidney graft recipients with normally functioning grafts showed significantly lower serum CXCL10 levels than patients who experienced graft failure, whereas no differences for serum CCL22 levels were observed. After the assignment of all patients to four groups according to serum CXCL10 levels, the death-censored survival rates of grafts were 97.5%, 93.6%, 89.7%, 78.7% (p = = 0.0006) at 5 years, while no influence was observed on patient survival. Accordingly, patients with the highest CXCL10 levels showed an increased frequency and severity of rejection episodes. Serum C-reactive protein (CRP) level was also assayed in the same samples. Increase of serum CRP levels represented a predictive parameter for death, but not for graft failure. Multivariate analysis demonstrated that among the analyzed variables, CXCL10 had the highest predictive power of graft loss (RR 2.787). Thus, measurement of pretransplant serum CXCL10 levels might represent a clinically useful parameter to identify subjects who are at high risk of severe rejection and graft failure.

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Section: Discussionsupporting

confidence: 71%

High Pretransplant Serum Levels of CXCL10/IP-10 Are Related to Increased Risk of Renal Allograft Failure

Rotondi¹,

Rosati²,

Buonamano³

et al. 2004

American Journal of Transplantation

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“…Data linking intragraft expression of CXCR3 and its ligands with development of acute and chronic cardiac allograft rejection were recently also reported by other groups [57][58][59]. In addition, elevated levels of the CXCR3 ligand, CXCL11, were associated with the development of coronary artery transplant vasculopathy [60], whereas serum levels of MCP-1/CCL2, although raised, were not [61]. A recent study provided the first direct evidence that persistent elevation of CXCL10 and CXCL11 in human cardiac allografts is associated with the development of chronic rejection.…”

Section: Cxcr3-binding Chemokines In Engraftment and Allograft Survivalsupporting

confidence: 58%

CXCR3-binding Chemokines: Novel Multifunctional Therapeutic Targets

Lazzeri

Romagnani²

2005

curr drug targets immune endocr metabol disord

106

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The goal to attenuate inflammation without inducing generalized immunosuppression has focused the attention on chemokines, a family of chemotactic peptides that regulate the leukocyte traffick into tissues. However, the development of drugs that block ckemokine activity may be hampered by the observation that some chemokines display pleiotropic biologic functions. For example, the chemokines CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC exhibit the ability to recruit different leukocytes subsets, the capacity to induce the proliferation of vascular pericytes as well as powerful anti-tumor effects, which are mediated by a common receptor, named CXCR3. Because of their pleiotropic biologic effects, these chemokines have been proposed as possible therapeutic targets in cancer, allograft rejection, glomerulonephritis, diabetes, multiple sclerosis, and autoimmune disorders of the thyroid. The chemokine CXCL4/PF4 shares several activities with CXCL9, CXCL10, and CXCL11, including angiostatic effects, although its specific receptor has remained unknown for a long time. Recently, we provided evidence that the different functions of CXCL9, CXCL10, and CXCL11 on distinct cell types can be at least partly explained by the interaction of these chemokines with two distinct receptors. Indeed, in addition to the classic form of CXCR3 receptor, which we have renamed as CXCR3-A, a novel CXCR3 receptor variant (CXCR3-B) was identified, that not only mediates the angiostatic activity of CXCR3 ligands, but also acts as functional receptor for CXCL4. In this review, we focus on the accumulating evidence demonstrating the pivotal role of CXCR3-binding chemokines in several human diseases. Studies based on CXCR3 targeting have shown its importance in different pathologic conditions and orally active small molecules capable of inhibiting this receptor are now being developed in order to be tested for their activity in humans.

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“…88 Finally, although inflammation and vascular remodeling appear to play an important pathogenic role in the development of CAV, few studies have examined the predictive value of chemokine measurements, and the results are somewhat conflicting. 89,90 These studies are also hampered by methodological flaws by using coronary angiography instead of intravascular ultrasound (IVUS) for CAV diagnosing and evaluation.…”

Section: Chemokines As Predictor Restenosis and Cardiac Allograft Vasmentioning

confidence: 99%

Chemokines and Cardiovascular Risk

Aukrust

Halvorsen

Yndestad

et al. 2008

ATVB

166

135

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Abstract-Based on the importance of inflammation in atherogenesis, recent work has focused on whether plasma markers of inflammation can noninvasively diagnose and prognosticate atherosclerotic disorders. Although several studies support an important pathogenic role of chemokines in atherosclerosis, potentially representing attractive therapeutic targets in atherosclerotic disorders, this does not necessarily mean that chemokines are suitable parameters for risk prediction. In fact, the ability to reflect upstream inflammatory activity, stable levels in individuals, and high stability of the actual protein (eg, long half-life and negligible circadian variation) are additional important criteria for an ideal biomarker in cardiovascular disease. Although plasma/serum levels of certain chemokines (eg, interleukin-8/CXCL8 and monocyte chemoattractant protein-1/CCL2) have shown to be predictive for future cardiac events in some studies, their role as clinical biomarkers is unclear, and their ability to predict subclinical atherosclerosis has been disappointing. Further prospective studies, including a larger number of patients, are needed to make any firm conclusion. Based on the participation of several chemokines in atherogenesis, it is possible that in the future, combined measurements of multiple chemokines could reveal as a "signature of disease" that can serve as a highly accurate method to assess for the presence of atherosclerotic disease.

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Circulating monocyte chemoattractant protein-1 in heart transplant recipients with cardiac allograft vasculopathy

Cited by 5 publications

References 8 publications

High Pretransplant Serum Levels of CXCL10/IP-10 Are Related to Increased Risk of Renal Allograft Failure

High Pretransplant Serum Levels of CXCL10/IP-10 Are Related to Increased Risk of Renal Allograft Failure

CXCR3-binding Chemokines: Novel Multifunctional Therapeutic Targets

Chemokines and Cardiovascular Risk

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