Pentraxin-3: An Easily Measurable Soluble Factor to Improve Post-Transplant Graft Versus Host Disease Monitoring and Management.

Allogeneic haemopoietic-stem-cell transplantation (HSCT) is the treatment of choice for many malignant and non-malignant disorders. Despite the recent advances in post-transplantat immunosuppressive therapy, Graft-versus-Host Disease (GVHD) still represents the major life-threatening complication, developing in a substantial number of HSCT patients and resulting in poor outcome. The basis of GVHD pathophysiology are still poorly understood and its current diagnosis depends mainly on clinical manifestations and invasive biopsies. Specific biomarkers for GVHD would facilitate the early and accurate recognition of this invalidating disease as well as the monitoring of patient response to adopted anti-GVHD pharmacological treatment. With the aim to explore new reliable markers for predicting and monitoring GVHD course, we focused on pentraxin-3 (PTX-3), an acute-phase protein, that has been shown to play a crucial role in orchestrating inflammatory immune responses.

Having obtained an informed consent, we collected plasma samples from 46 patients who received unmanipulated HSCT and from 9 healthy donors (HD) volunteers. After HSCT, 25/46 patients developed skin GVHD (18 acute GVHD and 7 chronic GVHD), while 21/46 never experienced it. Concerning GVHD patients, blood samples were collected at the day of GVHD onset/ flare, before the beginning of GVHD-specific drug therapy. PTX-3 plasma levels were monitored by ELISA assays.

Patients who did not develop GVHD after HSCT showed augmented PTX-3 plasma levels (mean=3.3 ng/ml, range=1.1-8.6 ng/ml) if compared to HD (mean=1.2 ng/ml, range=0.3-2.5 ng/ml, p<0.01). Interestingly, we observed a strong increase of PTX-3 plasma levels in patients with acute GVHD (mean=42.2 ng/ml, range=6.7-218.2 ng/ml) or with flair-ups of chronic GVHD (mean=15.8 ng/ml, range=9-44.3 ng/ml). The increase of PTX-3 levels in patients with acute and active chronic GVHD was statistically significant (p<0.01 and p<0.05 respectively) when compared to both HD and HSCT patients without GVHD.

These preliminary results suggest that PTX-3 plasma levels increase very rapidly in patients experiencing active GVHD, thus candidating PTX-3 as an easily measurable soluble factor useful to corroborate clinical observations in a disease in which signs and symptoms are often protean. Further studies are needed to clarify if PTX-3 could represent a good diagnostic and/or prognostic factor rapidly indicating therapy responsiveness.

No relevant conflicts of interest to declare.