Tick-Borne Encephalitis Specific Lymphocyte Response after Allogeneic Hematopoietic Stem Cell Transplantation Predicts Humoral Immunity after Vaccination
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population and Design
2.2. Institutional Review Board Statement
2.3. Study Endpoints
2.4. Laboratory Analyses
2.4.1. Collection and Storage of Peripheral Blood Mononuclear Cells
2.4.2. Lymphocyte Proliferation Detected by Thymidine Incorporation Assay
2.4.3. Flow Cytometric Analysis
2.4.4. Cytokine Detection Assays
2.4.5. Statistical Analyses
3. Results
3.1. Characteristics of the Study Population
3.2. Assessment of Lymphocyte Proliferation and Cytokine Responses after Antigen-Specific and Polyclonal Stimulation
3.2.1. Comparison between Patients and Healthy Control Subjects
3.2.2. Comparison of Patients with and without Humoral Response
3.2.3. Comparing Patients with Related and Unrelated Donors
3.3. Predictors for TBE Proliferation at Baseline before Vaccination
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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Subject No. | Group | Age In Years | Sex | BMI | Underlying Condition | Sibling Donor | Conditioning Regimen * | Neutralization Test Titer Baseline | Lymphocyte Proliferation after Stimulation With (SI) | Humoral Responder | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|
TBE Antigen | CEFT | PMA/Iono | ||||||||||
1 | Patient | 27 | F | 23.1 | AML | Yes | Myeloablative | 10 | 30.99 | 24.60 | 67.64 | Yes |
2 | Patient | 24 | M | 43.1 | AML | Yes | Myeloablative | 160 | 5.15 | 1.53 | 40.28 | No |
3 | Patient | 27 | M | 24.0 | ALL | Yes | Myeloablative | 95 | 4.15 | 2.61 | 60.44 | No |
4 | Patient | 56 | M | 31.5 | AML | No | Non-myeloablative | 40 | 2.22 | 1.13 | 66.28 | No |
5 | Patient | 61 | M | 29.0 | AML | Yes | Non-myeloablative | 48 | 13.06 | 24.65 | 77.40 | Yes |
6 | Patient | 27 | F | 39.1 | AML | No | Non-myeloablative | 113 | 28.45 | 21.69 | 54.37 | Yes |
7 | Patient | 47 | M | 29.9 | Lymphoma | No | Non-myeloablative | 6 | 1.02 | 36.13 | 322.35 | No |
8 | Patient | 22 | F | 19.5 | AML | Yes | Myeloablative | 538 | 24.34 | 34.67 | 132.59 | Yes |
9 | Patient | 53 | F | 22.7 | AML | No | Non-myeloablative | 12 | 1.53 | 1.24 | 72.24 | No |
10 | Patient | 43 | M | 27.8 | AML | No | Myeloablative | 40 | 1.21 | 2.21 | 71.54 | No |
11 | Patient | 22 | M | 23.1 | AML | No | Myeloablative | 40 | 1.04 | 3.47 | 94.69 | No |
12 | Patient | 26 | M | 26.9 | AA | Yes | Non-myeloablative | 10 | 3.35 | 14.59 | 153.72 | No |
13 | Patient | 41 | F | 24.2 | Lymphoma | Yes | Non-myeloablative | 10 | 9.42 | 1.57 | 532.10 | No |
14 | Patient | 55 | M | 28.4 | AML | No | Non-myeloablative | 4 | 1.45 | 1.39 | 64.81 | No |
15 | Patient | 58 | M | 32.4 | AML | No | Non-myeloablative | 80 | 1.44 | 8.55 | 190.69 | No |
16 | Patient | 26 | F | 19.1 | AML | Yes | Myeloablative | 135 | 69.70 | 45.20 | 171.94 | Yes |
17 | Patient | 31 | M | 23.4 | ALL | Yes | Myeloablative | 4 | 27.41 | 11.21 | 61.41 | Yes |
18 | Control | 27 | F | 18.5 | - | - | - | <5 | 0.98 | 134.64 | 271.29 | Yes |
19 | Control | 32 | M | 24.2 | - | - | - | <5 | 0.87 | 51.46 | 214.57 | Yes |
20 | Control | 22 | F | 20.3 | - | - | - | <5 | 0.89 | 77.62 | 374.98 | Yes |
21 | Control | 21 | F | 26.0 | - | - | - | <5 | 0.99 | 65.14 | 307.39 | Yes |
22 | Control | 23 | M | 22.2 | - | - | - | <5 | 2.31 | 13.34 | 314.67 | Yes |
23 | Control | 38 | F | 20.9 | - | - | - | <5 | 0.61 | 25.19 | 88.62 | Yes |
24 | Control | 33 | M | 21.1 | - | - | - | <5 | 1.27 | 45.24 | 85.41 | Yes |
25 | Control | 60 | M | 26.6 | - | - | - | <5 | 2.37 | 56.29 | 255.10 | No |
Logistic Regression Models for TBE Proliferation SI > 3 | |||||
---|---|---|---|---|---|
Variable | Comparison | OR | Lower 95% CI | Upper 95% CI | p-Value |
Humoral responder | Yes vs. No | 21.667 | 1.816 | 3090.366 | 0.012 |
Donor | Related vs. Unrelated | 95.000 | 6.437 | 15,251.370 | <0.001 |
Sex | Female vs. Male | 4.333 | 0.594 | 52.665 | 0.153 |
Chronic GvHD requiring systemic immunosuppressive treatment | Yes vs. No | 1.667 | 0.247 | 11.718 | 0.595 |
BMI | 0.981 | 0.847 | 1.134 | 0.784 | |
Age | 0.918 | 0.835 | 0.988 | 0.020 | |
Total CD4+ T-cell count at baseline | 1.004 | 0.997 | 1.014 | 0.241 |
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Harrison, N.; Grabmeier-Pfistershammer, K.; Graf, A.; Trapin, D.; Tauber, P.; Aberle, J.H.; Stiasny, K.; Schmidt, R.; Greinix, H.; Rabitsch, W.; et al. Tick-Borne Encephalitis Specific Lymphocyte Response after Allogeneic Hematopoietic Stem Cell Transplantation Predicts Humoral Immunity after Vaccination. Vaccines 2021, 9, 908. https://doi.org/10.3390/vaccines9080908
Harrison N, Grabmeier-Pfistershammer K, Graf A, Trapin D, Tauber P, Aberle JH, Stiasny K, Schmidt R, Greinix H, Rabitsch W, et al. Tick-Borne Encephalitis Specific Lymphocyte Response after Allogeneic Hematopoietic Stem Cell Transplantation Predicts Humoral Immunity after Vaccination. Vaccines. 2021; 9(8):908. https://doi.org/10.3390/vaccines9080908
Chicago/Turabian StyleHarrison, Nicole, Katharina Grabmeier-Pfistershammer, Alexandra Graf, Doris Trapin, Peter Tauber, Judith H. Aberle, Karin Stiasny, Ralf Schmidt, Hildegard Greinix, Werner Rabitsch, and et al. 2021. "Tick-Borne Encephalitis Specific Lymphocyte Response after Allogeneic Hematopoietic Stem Cell Transplantation Predicts Humoral Immunity after Vaccination" Vaccines 9, no. 8: 908. https://doi.org/10.3390/vaccines9080908