The Role of Programmed Cell Death 1/Programmed Death Ligand 1 (PD-1/PD-L1) Axis in Sepsis-Induced Apoptosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Patient Characteristics
2.2. Evaluated Parameters
- CD4/CD8/CD3 (BDTritest, Cat. No. 342414);
- CD3/CD16 + CD56/CD45/CD19 (BD Multitest, Cat. No. 342416).
2.3. Statistical Analysis
3. Results
3.1. Population Analysis
3.2. Comparison of Variables for the Entire Amount of Patients
3.3. Comparison of Variables for the Sepsis and Septic Shock Groups
3.4. Comparison of Variables for the Survivor and Non-Survivor Groups
3.5. Comparison of Variables for the Survivor and Non-Survivor Groups
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Underlying Conditions | Number of Patients | % | Infectious Site | Number of Patients | % |
---|---|---|---|---|---|
Cardiovascular disease | 73 | 83.91 | Pulmonary | 51 | 58.6 |
Renal disease | 58 | 69.88 | Abdominal | 30 | 34.5 |
Respiratory disease | 55 | 63.22 | Urinary tract | 10 | 11.5 |
Neurological disease | 42 | 48.28 | Cutaneous | 7 | 8.0 |
Diabetes | 27 | 31.03 | Thoracic cavity | 1 | 1.1 |
Trauma | 7 | 8.05 | Soft tissue | 1 | 1.1 |
Other | 85 | 97.70 | Unidentified | 1 | 1.1 |
Parameter (on Day 1) | PD-1 (ng/mL) | PD-L1 (ng/mL) |
---|---|---|
Th cells (CD4+) % | r = 0.1941 (−0.03038 to 0.4000) a p = 0.08 | r = 0.1378 (−0.09043 to 0.3523) p b = 0.24 |
Tc cells (CD8+) % | r = −0.2545 (−0.4520 to −0.03317) a p = 0.02 | r =−0.2263 (−0.4353 to 0.005916) a p = 0.04 |
Parameter (on day 5) | PD-1 (ng/mL) | PD-L1 (ng/mL) |
Th cells (CD4+) % | r = −0.1661 (−0.4397 to 0.1357) a p =0.27 | r = −0.3306 (−0.5793 to −0.02552) p b = 0.03 |
Tc cells (CD8+) % | r = 0.1366 (−0.1652 to 0.4150) a p = 0.36 | rho = 0.3982 (0.1032 to 0.6288) p b = 0.0099 |
Parameter | Th cells (CD4+) % on day 1 | Th cells (CD4+) % on day 5 |
Tc cells (CD8+) % | r = −0.7951 (−0.8631 to −0.6988) a p ≤ 0.0001 | r = −0.9558 (−0.9745 to −0.9238) p b ≤ 0.0001 |
Parameter (on Day 1) | PD-1 (ng/mL) | PD-L1 (ng/mL) |
---|---|---|
SOFA | r = 0.08570 (−0.1402 to 0.3031) a p = 0.44 | r= 0.3511 (0.1365 to 0.5343) p b = 0.001 |
APACHE II | r = 0.1346 (−0.09132 to 0.3474) a p = 0.2278 | r = 0.2822 (0.06065 to 0.4773) a p = 0.01 |
Parameter (on day 5) | PD-1 (ng/mL) | PD-L1 (ng/mL) |
SOFA | r = 0.06812 (−0.2350 to 0.3592) a p = 0.65 | r = 0.03967 (−0.2752 to 0.3469) p b = 0.80 |
APACHE II | r = 0.1019 (−0.2026 to 0.3885) a p = 0.5 | rho = 0.1580 (−0.1615 to 0.4475) p b = 0.33 |
Parameter | SOFA on day 1 | SOFA on day 5 |
APACHE II | r = 0.7394 (0.6263 to 0.8220) p b ≤ 0.0001 | r = 0.7726 (0.6297 to 0.8649) p b ≤ 0.0001 |
Tc Cells (CD8+) % | PD-1, ng/mL | PD-L1, ng/mL | SOFA | APACHE II | ||
---|---|---|---|---|---|---|
Th cells (CD4+) % | Day 1 | r = −0.8654 (−0.9188 to −0.7809) p b < 0.0001 | r = 0.1386 (−0.1449 to 0.4010) a p = 0.3224 | r = 0.1374 (−0.1496 to 0.4030) p b = 0.3466 | r = 0.08207 (−0.1824 to 0.3355) p b = 0.5439 | r = 0.09483 (−0.1699 to 0.3468) p b = 0.4829 |
Day 5 | r = −0.9776 (−0.9887 to −0.9557) p b < 0.0001 | r = −0.2788 (−0.5881 to 0.1016) a p = 0.1357 | r = −0.001538 (−0.4068 to 0.4042) a p = 0.9942 | r = 0.01774 (−0.3330 to 0.3642) p b = 0.9232 | r = 0.01039 (−0.3395 to 0.3578) p b = 0.9550 | |
Tc cells (CD8+) % | Day 1 | r = −0.1885 (−0.4431 to 0.09433) a p = 0.1765 | r = −0.2057 (−0.4603 to 0.08011) p b = 0.1562 | r = −0.1455 (−0.3913 to 0.1196) p b = 0.2801 | r = −0.1744 (−0.4161 to 0.09023) p b = 0.1944 | |
Day 5 | r = 0.2487 (−0.1336 to 0.5665) a p = 0.1852 | r = 0.1078 (−0.3113 to 0.4918) a p = 0.6081 | r = −0.08839 (−0.4240 to 0.2686) p b = 0.6305 | r = −0.06552 (−0.4050 to 0.2898) p b = 0.7216 | ||
PD-1, ng/mL | Day 1 | r = 0.002837 (−0.2958 to 0.3010) a p = 0.9851 | r = −0.004792 (−0.2823 to 0.2734) a p = 0.9728 | r = 0.2031 (−0.07920 to 0.4553) a p = 0.1446 | ||
Day 5 | r = −0.06957 (−0.4700 to 0.3546) a p = 0.7467 | r = −0.04681 (−0.4096 to 0.3288) a p = 0.8060 | r = 0.05985 (−0.3171 to 0.4205) a p = 0.7534 | |||
PD-L1, ng/mL | Day 1 | r = 0.2086 (−0.07714 to 0.4626) p b = 0.1504 | r = 0.2338 (−0.05075 to 0.4832) p b = 0.1059 | |||
Day 5 | r = 0.003482 (−0.4026 to 0.4084) a p = 0.9868 | r = 0.2367 (−0.1868 to 0.5859) a p = 0.2547 | ||||
SOFA | Day 1 | r = 0.7225 (0.5691 to 0.8273) p b < 0.0001 | ||||
Day 5 | r = 0.7294 (0.5193 to 0.8563) p b < 0.0001 |
Tc Cells (CD8+) % | PD-1, ng/mL | PD-L1, ng/mL | SOFA | APACHE II | ||
---|---|---|---|---|---|---|
Th cells (CD4+) % | Day 1 | r = −0.4830 (−0.7183 to −0.1486) p b = 0.0069 | r = 0.2340 (−0.1561 to 0.5609) a p = 0.2219 | r = 0.06571 (−0.3224 to 0.4349) p b = 0.7447 | r = 0.03528 (−0.3292 to 0.3906) p b = 0.8532 | r = 0.05343 (−0.3129 to 0.4059) p b = 0.7792 |
Day 5 | r = −0.9042 (−0.9653 to −0.7491) p b < 0.0001 | r = −0.03431 (−0.5180 to 0.4660) a p = 0.8984 | r = −0.4075 (−0.7514 to 0.1105) p b = 0.1172 | r = 0.07724 (−0.4351 to 0.5518) p b = 0.7762 | r = 0.001199 (−0.4948 to 0.4966) p b = 0.9965 | |
Tc cells (CD8+) % | Day 1 | r = −0.3345 (−0.6313 to 0.04784) a p = 0.0761 | r = −0.04149 (−0.4150 to 0.3439) p b = 0.8372 | r = −0.1220 (−0.4620 to 0.2492) p b = 0.5206 | r = 0.01866 (−0.3439 to 0.3764) p b = 0.9220 | |
Day 5 | r = −0.02696 (−0.5126 to 0.4718) a p = 0.9209 | r = 0.4329 (−0.08000 to 0.7645) p b = 0.0940 | r = −0.09829 (−0.5664 to 0.4178) p b = 0.7173 | r = −0.03894 (−0.5245 to 0.4658) p b = 0.8861 | ||
PD-1, ng/mL | Day 1 | r = 0.4566 (0.07218 to 0.7230) a p = 0.0190 | r = 0.1846 (−0.2060 to 0.5244) a p = 0.3378 | r = 0.06407 (−0.3199 to 0.4300) a p = 0.7413 | ||
Day 5 | r = 0.3088 (−0.2359 to 0.7059) a p = 0.2440 | r = 0.3333 (−0.2099 to 0.7193) a p = 0.2058 | r = 0.1372 (−0.3983 to 0.6029) a p = 0.6101 | |||
PD-L1, ng/mL | Day 1 | r = 0.4909 (0.1363 to 0.7340) p b = 0.0093 | r = 0.3373 (−0.04903 to 0.6358) p b = 0.0854 | |||
Day 5 | r = 0.1272 (−0.4119 to 0.6003) p b = 0.6515 | r = 0.1370 (−0.4036 to 0.6067) p b = 0.6263 | ||||
SOFA | Day 1 | r = 0.8070 (0.6298 to 0.9043) p b < 0.0001 | ||||
Day 5 | r = 0.8433 (0.5972 to 0.9443) p b < 0.0001 |
Tc Cells (CD8+) % | PD-1, ng/mL | PD-L1, ng/mL | SOFA | APACHE II | ||
---|---|---|---|---|---|---|
Th cells (CD4+) % | Day 1 | r = −0.9368 (−0.9726 to −0.8575) p b < 0.0001 | r = −0.2344 (−0.5910 to 0.1988) a p = 0.2703 | r = 0.1030 (−0.3679 to 0.5319) a p = 0.6655 | r = 0.07439 (−0.3392 to 0.4639) p b = 0.7298 | r = −0.09935 (−0.4834 to 0.3167) p b = 0.6442 |
Day 5 | r = −0.9788 (−0.9922 to −0.9426) p b < 0.0001 | r = 0.05296 (−0.4547 to 0.5346) p b = 0.8456 | r = −0.06786 (−0.5720 to 0.4735) a p = 0.8124 | r = −0.1823 (−0.6600 to 0.4004) a p = 0.5303 | r = −0.2830 (−0.7074 to 0.2913) p b = 0.3268 | |
Tc cells (CD8+) % | Day 1 | r = 0.1723 (−0.2602 to 0.5472) a p = 0.4207 | r = −0.07446 (−0.5110 to 0.3926) a p = 0.7550 | r = −0.1931 (−0.5534 to 0.2280) p b = 0.3659 | r = 0.008656 (−0.3961 to 0.4106) p b = 0.9680 | |
Day 5 | r = −0.01212 (−0.5048 to 0.4865) p b = 0.9645 | r = 0.1893 (−0.3722 to 0.6493) a p = 0.4983 | r = 0.1170 (−0.4549 to 0.6206) a p = 0.6894 | r = 0.3229 (−0.2506 to 0.7286) p b = 0.2602 | ||
PD-1, ng/mL | Day 1 | r = −0.1835 (−0.5882 to 0.2948) a p = 0.4388 | r = 0.02186 (−0.3957 to 0.4319) a p = 0.9193 | r = −0.1161 (−0.5057 to 0.3129) a p = 0.5892 | ||
Day 5 | r = 0.05934 (−0.4998 to 0.5836) a p = 0.8438 | r = 0.2519 (−0.3633 to 0.7141) a p = 0.4044 | r = 0.006637 (−0.5463 to 0.5556) p b = 0.9828 | |||
PD-L1, ng/mL | Day 1 | r = −0.05898 (−0.4994 to 0.4056) a p = 0.8049 | r = −0.07472 (−0.5111 to 0.3923) a p = 0.7542 | |||
Day 5 | r = −0.1015 (−0.6495 to 0.5159) a p = 0.7583 | r = −0.2050 (−0.7067 to 0.4339) a p = 0.5201 | ||||
SOFA | Day 1 | r = 0.7352 (0.4718 to 0.8782) p b < 0.0001 | ||||
Day 5 | r = 0.8397 (0.5452 to 0.9497) p b = 0.0003 |
Tc Cells (CD8+) % | PD-1, ng/mL | PD-L1, ng/mL | SOFA | APACHE II | ||
---|---|---|---|---|---|---|
Th cells (CD4+) % | Day 1 | r = −0.7114 (−0.8155 to −0.5629) p b < 0.0001 | r = 0.3463 (0.08886 to 0.5603) a p = 0.0078 | r = 0.1843 (−0.08264 to 0.4265) p b = 0.1740 | r = 0.1454 (−0.1062 to 0.3795) p b = 0.2556 | r = 0.1835 (−0.06737 to 0.4125) p b = 0.1501 |
Day 5 | r = −0.9461 (−0.9730 to −0.8939) p b < 0.0001 | r = −0.4123 (−0.6749 to −0.05702) a p = 0.0212 | r = −0.2116 (−0.5536 to 0.1915) p b = 0.2995 | r = 0.02640 (−0.3146 to 0.3613) p b = 0.8822 | r = 0.01088 (−0.3285 to 0.3478) p b = 0.9513 | |
Tc cells (CD8+) % | Day 1 | r = −0.3873 (−0.5920 to −0.1357) a p = 0.0027 | r = −0.2790 (−0.5049 to −0.01736) p b = 0.0373 | r = −0.2283 (−0.4506 to 0.02059) p b = 0.0719 | r = −0.1836 (−0.4126 to 0.06722) p b = 0.1498 | |
Day 5 | r = 0.3414 (−0.02566 to 0.6273) a p = 0.0602 | r = 0.2440 (−0.1584 to 0.5768) p b = 0.2297 | r = −0.1121 (−0.4338 to 0.2350) p b = 0.5280 | r = −0.1009 (−0.4246 to 0.2457) p b = 0.5703 | ||
PD-1, ng/mL | Day 1 | r = 0.2528 (−0.02984 to 0.4980) a p = 0.0706 | r = 0.1357 (−0.1347 to 0.3873) a p = 0.3097 | r= 0.2432 (−0.02392 to 0.4779) a p = 0.0658 | ||
Day 5 | r = 0.03316 (−0.3693 to 0.4251) a p = 0.8722 | r = 0.05831 (−0.3005 to 0.4026) a p = 0.7472 | r = 0.1770 (−0.1872 to 0.4985) a p = 0.3243 | |||
PD-L1, ng/mL | Day 1 | r = 0.4850 (0.2545 to 0.6633) p b = 0.0002 | r = 0.3710 (0.1198 to 0.5776) p b = 0.0049 | |||
Day 5 | r = −0.004608 (−0.3770 to 0.3691) p b = 0.9814 | r = 0.1172 (−0.2676 to 0.4697) p b = 0.5526 | ||||
SOFA | Day 1 | r = 0.6471 (0.4756 to 0.7712) p b < 0.0001 | ||||
Day 5 | r = 0.6939 (0.4733 to 0.8326) p b < 0.0001 |
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Coman, O.; Grigorescu, B.-L.; Huțanu, A.; Bacârea, A.; Văsieșiu, A.M.; Fodor, R.Ș.; Stoica, F.; Azamfirei, L. The Role of Programmed Cell Death 1/Programmed Death Ligand 1 (PD-1/PD-L1) Axis in Sepsis-Induced Apoptosis. Medicina 2024, 60, 1174. https://doi.org/10.3390/medicina60071174
Coman O, Grigorescu B-L, Huțanu A, Bacârea A, Văsieșiu AM, Fodor RȘ, Stoica F, Azamfirei L. The Role of Programmed Cell Death 1/Programmed Death Ligand 1 (PD-1/PD-L1) Axis in Sepsis-Induced Apoptosis. Medicina. 2024; 60(7):1174. https://doi.org/10.3390/medicina60071174
Chicago/Turabian StyleComan, Oana, Bianca-Liana Grigorescu, Adina Huțanu, Anca Bacârea, Anca Meda Văsieșiu, Raluca Ștefania Fodor, Florin Stoica, and Leonard Azamfirei. 2024. "The Role of Programmed Cell Death 1/Programmed Death Ligand 1 (PD-1/PD-L1) Axis in Sepsis-Induced Apoptosis" Medicina 60, no. 7: 1174. https://doi.org/10.3390/medicina60071174