| 1. |
- Christakoudi, Sofia, et al.
(författare)
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Development and validation of the first consensus gene-expression signature of operational tolerance in kidney transplantation, incorporating adjustment for immunosuppressive drug therapy
- 2020
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Kidney transplant recipients (KTRs) with "operational tolerance" (OT) maintain a functioning graft without immunosuppressive (IS) drugs, thus avoiding treatment complications. Nevertheless, IS drugs can influence gene-expression signatures aiming to identify OT among treated KTRs. Methods: We compared five published signatures of OT in peripheral blood samples from 18 tolerant, 183 stable, and 34 chronic rejector KTRs, using gene-expression levels with and without adjustment for IS drugs and regularised logistic regression. Findings: IS drugs explained up to 50% of the variability in gene-expression and 20-30% of the variability in the probability of OT predicted by signatures without drug adjustment. We present a parsimonious consensus gene-set to identify OT, derived from joint analysis of IS-drug-adjusted expression of five published signature gene-sets. This signature, including CD40, CTLA4, HSD11B1, IGKV4-1, MZB1, NR3C2, and RAB40C genes, showed an area under the curve 0.92 (95% confidence interval 0.88-0.94) in cross-validation and 0.97 (0.93-1.00) in six months follow-up samples. Interpretation: We advocate including adjustment for IS drug therapy in the development stage of gene-expression signatures of OT to reduce the risk of capturing features of treatment, which could be lost following IS drug minimisation or withdrawal. Our signature, however, would require further validation in an independent dataset and a biomarker-led trial. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license. (http://creativecommons.org/licenses/by/4.0/)
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| 2. |
- Christakoudi, Sofia, et al.
(författare)
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Steroid regulation : An overlooked aspect of tolerance and chronic rejection in kidney transplantation
- 2018
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Ingår i: Molecular and Cellular Endocrinology. - : ELSEVIER IRELAND LTD. - 0303-7207 .- 1872-8057. ; 473, s. 205-216
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Tidskriftsartikel (refereegranskat)abstract
- Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-qPCR-based) and cell counts were adjusted for immunosuppressant drug intake. Tolerant (n = 17), stable (n = 190) and CR patients (n = 37) were compared. Healthy controls (n= 14) were used as reference. The anti-inflammatory glucocorticoid receptor (NR3C1) and the cortisol-activating HSD11B1 and H6PD genes were up-regulated in CR and were lowest in tolerant patients. The pro-inflammatory mineralocorticoid gene (NR3C2) was downregulated in stable and CR patients. NR3C1 was associated with neutrophils and NR3C2 with T-cells. Steroid conversion and receptor genes, alone, enabled classification of tolerant patients and were major contributors to gene-expression signatures of both, tolerance and CR, alongside known tolerance-associated genes, revealing a key role of steroid regulation and response in kidney transplantation.
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| 3. |
- Lamperti, I., et al.
(författare)
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SUPER: V. ALMA continuum observations of z ∼2 AGN and the elusive evidence of outflows influencing star formation
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
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Tidskriftsartikel (refereegranskat)abstract
- We study the impact of active galactic nuclei (AGN) ionised outflows on star formation in high-redshift AGN host galaxies, by combining near-infrared integral field spectroscopic (IFS) observations, mapping the H emission and [O iii]5007 outflows, with matched-resolution observations of the rest-frame far-infrared (FIR) emission.We present high-resolution ALMA Band 7 observations of eight X-ray selected AGN (L2-10 keV = 1043:81045:2 erg s1) at z 2 from the SUPER (SINFONI Survey for Unveiling the Physics and Eect of Radiative feedback) sample, targeting the observed-frame 870 m (rest-frame 260 m) continuum at 2 kpc (0.200) spatial resolution. The targets were selected among the SUPER AGN with an [O iii] detection in the IFS maps and with a detection in the FIR photometry. We detected six out of eight targets with signal-to-noise ratio S=N & 10 in the ALMA maps, from which we measured continuum flux densities in the range 0:272:58 mJy and FIR half-light radii (Re) in the range 0:8-2:1 kpc. The other two targets were detected with S/N of 3.6 and 5.9, which are insucient for spatially resolved analysis. The FIR Re of our sample are comparable to other AGN and star-forming galaxies at a similar redshift from the literature. However, combining our sample with the literature samples, we find that the mean FIR size in X-ray AGN (Re = 1:16 0:11 kpc) is slightly smaller than in non-AGN (Re = 1:69 0:13 kpc). From spectral energy distribution fitting, we find that the main contribution to the 260 m flux density is dust heated by star formation, with 4% contribution from AGN-heated dust and 1% from synchrotron emission. The majority of our sample show dierent morphologies for the FIR (mostly due to reprocessed stellar emission) and the ionised gas emission (H and [O iii], mostly due to AGN emission). This could be due to the dierent locations of dust and ionised gas, the dierent sources of the emission (stars and AGN), or the eect of dust obscuration.We are unable to identify any residual H emission, above that dominated by AGN, that could be attributed to star formation. Under the assumption that the FIR emission is a reliable tracer of obscured star formation, we find that the obscured star formation activity in these AGN host galaxies is not clearly aected by the ionised outflows. However, we cannot rule out that star formation suppression is happening on smaller spatial scales than the ones we probe with our observations (<2 kpc) or on dierent timescales.
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| 4. |
- Pereira-Santaella, M., et al.
(författare)
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Physics of ULIRGs with MUSE and ALMA: The PUMA project: II. Are local ULIRGs powered by AGN: The subkiloparsec view of the 220 GHz continuum
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 651
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Tidskriftsartikel (refereegranskat)abstract
- We analyze new high-resolution (400 pc) ∼220 GHz continuum and CO(2-1) Atacama Large Millimeter Array (ALMA) observations of a representative sample of 23 local (z < 0.165) ultra-luminous infrared systems (ULIRGs; 34 individual nuclei) as part of the "Physics of ULIRGs with MUSE and ALMA"(PUMA) project. The deconvolved half-light radii of the ∼220 GHz continuum sources, rcont, are between < 60 pc and 350 pc (median 80-100 pc). We associate these regions with the regions emitting the bulk of the infrared luminosity (LIR). The good agreement, within a factor of 2, between the observed ∼220 GHz fluxes and the extrapolation of the infrared gray-body as well as the small contributions from synchrotron and free-free emission support this assumption. The cold molecular gas emission sizes, rCO, are between 60 and 700 pc and are similar in advanced mergers and early interacting systems. On average, rCO are ∼2.5 times larger than rcont. Using these measurements, we derived the nuclear LIR and cold molecular gas surface densities (ςLIR = 1011.5-1014.3 L· kpc-2 and ςH2 = 102.9-104.2 M· pc-2, respectively). Assuming that the LIR is produced by star formation, the median ςLIR corresponds to ςSFR = 2500 M· yr-1 kpc-2. This ςSFR implies extremely short depletion times, ςH2/ςSFR < 1-15 Myr, and unphysical star formation efficiencies > 1 for 70% of the sample. Therefore, this favors the presence of an obscured active galactic nucleus (AGN) in these objects that could dominate the LIR. We also classify the ULIRG nuclei in two groups: (a) compact nuclei (rcont < 120 pc) with high mid-infrared excess emission (ΔL6-20 μm/LIR) found in optically classified AGN; and (b) nuclei following a relation with decreasing ΔL6-20 μm/LIR for decreasing rcont. The majority, 60%, of the nuclei in interacting systems lie in the low-rcont end (<120 pc) of this relation, while this is the case for only 30% of the mergers. This suggests that in the early stages of the interaction, the activity occurs in a very compact and dust-obscured region while, in more advanced merger stages, the activity is more extended, unless an optically detected AGN is present. Approximately two-thirds of the nuclei have nuclear radiation pressures above the Eddington limit. This is consistent with the ubiquitous detection of massive outflows in local ULIRGs and supports the importance of the radiation pressure in the outflow launching process.
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