The expression of a group of proteins, haptoglobin (Hp), alpha-1-antitrypsin, apolipoprotein A-IV, serum paraoxonase and Zn-alpha-glycoprotein were increased and the proteins, clusterin precursor, alpha-2-macroglobulin, serum amyloid protein precursor, sex hormone-binding globulin, serotransferrin and complement C4 were decreased in patients with extensive chronic GVHD (cGVHD).
In six patients who were in continuous remission after BMT, a rapid decrease in BCR-ABL copy number to the PCR-negative status was observed after the development of chronic GVHD.
In a logistic regression based on multinomial model, ATA/ATA homozygote had 7-fold increasing risk of the development of chronic GVHD compared with ACC/ACC homozygote.
In this report, an extensive evaluation of a patient with cGvHD is described: glucose and insulin during OGTT, markers of inflammation, adiponectin and RBP4, body composition analysis, and the kinetics of GLUT3 and GLUT4 in circulating monocytes were evaluated.
Findings suggest the potential utility of administering patient-reported and performance-based functional measures, such as the DASH and the AMPS, to patients with cGVHD.
We demonstrated that fibroblasts expressed angiotensin II, AT1R, and AT2R, and that the mRNA expression of angiotensinogen was greater in the lacrimal glands of cGVHD model mice than in controls generated by syngeneic-HSCT.
Next, we administered an AT1R antagonist (valsartan; 10 mg/kg) or angiotensin II type 2 receptor (AT2R) antagonist (PD123319; 10 mg/kg) intraperitoneally into cGVHD model mice and assessed the fibrotic change in the lacrimal gland, lung, and liver.
We demonstrated that fibroblasts expressed angiotensin II, AT1R, and AT2R, and that the mRNA expression of angiotensinogen was greater in the lacrimal glands of cGVHD model mice than in controls generated by syngeneic-HSCT.
In addition markers like ANK3 (ankyrin), S100A8 and VCAN are indicative for acute GvHD, while IFIT3, IFI44 and IFIT1 are potential biomarkers for chronic GvHD.
Analysis focused on previously identified cGVHD cellular biomarkers, including naive helper T (Th) cells, recent thymic emigrant (RTE) Th cells, CD21<sup>low</sup> B cells, CD56<sup>bright</sup> NK<sub>reg</sub> cells, and T<sub>reg</sub> cells ST2, osteopontin, sBAFF, sCD25, TIM-3, matrix metallopeptidase 3, ICAM-1, CXCL10, and soluble aminopeptidase N. The ATG-treated group had a >10-fold decrease in both RTE naive Th and naive Th cells (P < .0001) and a 10-fold increase in CD56<sup>bright</sup> NK<sub>reg</sub> cells (P < .0001).
The incidence of grade 3-4 acute GVHD was 11.8% in MUD and 3.8% in MMUD group, and that of NIH stage moderate/severe chronic GVHD in the 2 groups was 10.5% and 7.6%, respectively.
It is noteworthy that RT-PCR positivity appeared in five patients presenting acute or chronic graft versus host disease (GVHD) and in one patient who had received MUD-BMT.
The expression of a group of proteins, haptoglobin (Hp), alpha-1-antitrypsin, apolipoprotein A-IV, serum paraoxonase and Zn-alpha-glycoprotein were increased and the proteins, clusterin precursor, alpha-2-macroglobulin, serum amyloid protein precursor, sex hormone-binding globulin, serotransferrin and complement C4 were decreased in patients with extensive chronic GVHD (cGVHD).
A univariate logistic regression model analysis showed that only acute graft-versus-host disease may be affected by recipient MiHAg-HA-1 disparity (p: 0.041, OR: 6.727), while chronic graft-versus-host disease correlates with both age and recipient/donor sex mismatch (p: 0.014, OR: 8.556 and p: 0.033, OR: 8.664, respectively).
These results provide a strong rationale that blockade of p40 may represent a promising therapeutic strategy in preventing and treating aGVHD and cGVHD while sparing the GVL effect after allo-HSCT.
These results provide a strong rationale that blockade of p40 may represent a promising therapeutic strategy in preventing and treating aGVHD and cGVHD while sparing the GVL effect after allo-HSCT.
We created humanised mice model for chronic GVHD (cGVHD) by injecting cord blood (CB)-derived human CD34<sup>+</sup>CD38<sup>-</sup>CD45RA<sup>-</sup> haematopoietic stem/progenitor cells (HSPCs) into hIL-6 transgenic NOD/SCID/Il2rgKO (NSG) newborns, and compared GVHD progression with NSG newborns receiving CB CD34<sup>-</sup> cells mimicking acute GVHD.
Moreover, our data show that aGVHD, cGVHD patients and healthy donors (HDs) present distinct NK patterns: aGVHD patients have a higher frequency of CD56<sup>bri</sup> NK subsets with stronger NKG2D and CD62L expression, while CD56<sup>-</sup>CD16<sup>+</sup> NK cells with higher expression of CD57 and CD11b stand out as a signature population for cGVHD.
The therapeutic potential of targeted ROCK2 inhibition in the clinic was solidified further by human data demonstrating the KD025 inhibits the secretion of IL-21, IL-17, and interferon γ along with decreasing phosphorylated STAT3 and reduced protein expression of interferon regulatory factor 4 and B-cell lymphoma 6 (BCL6) in human peripheral blood mononuclear cells purified from active cGVHD patients.