Antigen-Induced IL-1RA Production Discriminates Active and Latent Tuberculosis Infection
Abstract
:1. Background
2. Patients and Methods
2.1. Human Subjects
2.2. Antigens
2.3. PBMC Isolation and Peptide Stimulation
2.4. Luminex Cytokine Detection
2.5. Statistical Analysis
2.5.1. Normality Test
2.5.2. Bivariate and Multivariate Analysis
2.5.3. The Area under the Curve (AUC)
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | ATBD (%) | LTBI (%) | Total n | p-Value |
---|---|---|---|---|
Gender | ||||
Male | 73 (77.7) | 21 (22.3) | 94 | 0.051 † |
Female | 46 (63.9) | 26 (36.1) | 72 | |
Age | ||||
12–17 years | 1 (50) | 1 (50) | 2 | <0.001 ‡ |
18–29 years | 76 (87.4) | 11 (12.6) | 87 | |
30 or more years | 42 (54.5) | 35 (45.5) | 77 | |
Ethnicity | ||||
Caucasian | 6 (75.0) | 2 (25.0) | 8 | 1.000 ‡ |
Mestizo | 113 (71.5) | 45 (28.5) | 158 | |
Marital status | ||||
Single | 63 (82.9) | 13 (17.1) | 76 | 0.008 ‡ |
Married | 17 (54.8) | 14 (45.2) | 31 | |
Cohabiting | 0 (0.0) | 1 (100) | 1 | |
Separated | 2 (66.7) | 1 (33.3) | 3 | |
Divorced | 37 (67.3) | 18 (32.7) | 55 | |
Education | ||||
None | 1 (100) | 0 (0.0) | 1 | <0.001 ‡ |
Primary | 7 (70.0) | 3 (30.0) | 10 | |
High school | 99 (83.9) | 19 (16.1) | 118 | |
Technical | 9 (34.6) | 17 (65.4) | 26 | |
University degree | 3 (27.3) | 8 (72.7) | 11 | |
Work | ||||
Unemployed | 2 (100) | 0 (0.0) | 2 | <0.001 ‡ |
Student | 13 (72.2) | 5 (27.8) | 18 | |
House worker | 29 (90.6) | 3 (9.4) | 32 | |
Temporal worker | 7 (70.0) | 3 (30.0) | 10 | |
Health care worker | 2 (11.1) | 16 (88.9) | 18 | |
Public/private worker | 42 (80.8) | 10 (19.2) | 52 | |
Independent worker | 24 (70.6) | 10 (29.4) | 34 | |
Comorbidities | ||||
None | 80 (71.4) | 32 (28.6) | 112 | 1.000 ‡ |
Yes | 39 (72.2) | 15 (27.8) | 54 | |
Total | 119 (71.7) | 47 (28.3) | 166 |
Cytokines and Peptides Combined | LTBI | ATBD | p-Value * |
---|---|---|---|
Rv0849-12 | |||
IL-1RA | 0.48 (0.0–1.87) | 5.57 (0.0–84.45) | 0.001 |
IP-10 | 8.72 (0.0–15.01) | 1.09 (0.0–10.60) | 0.054 |
MCP-1 | 46.87 (0.0–408.52) | 361.73 (48.60–1447.92) | 0.003 |
Rv2031c-14 | |||
IL-1RA | 0.51 (0.0–1.18) | 13.55 (0.26–73.2) | 0.001 |
Rv2031c-5 | |||
IL-1RA | 0.47 (0.0–1.42) | 4.51 (0.0–84.50) | 0.006 |
IL-8 | 189.6 (26.91–441.22) | 368.65 (92.22–1611.75) | 0.041 |
MCP-3 | 14.13 (2.23–45.15) | 30.53 (9.46–132.49) | 0.033 |
GRO | 45.57 (8.05–139.76) | 105.35 (21.05–579.55) | 0.017 |
EGF | 1.57 (0.0–6.71) | 7.78 (0.0–28.99) | 0.030 |
Rv2693-06 | |||
IL-1RA | 0.06 (0.0–1.87) | 4.78 (0.0–69.27) | 0.001 |
IL-8 | 168.23 (43.61–368.22) | 266.01 (123.42–1031.04) | 0.038 |
MCP-1 | 42.15 (0.0–656.25) | 468.47 (0.0–1689.57) | 0.029 |
GRO | 33.11 (9.28–94.95) | 77.50 (21.21–259.76) | 0.036 |
EGF | 0 (0.0–4.95) | 6.17 (0.0–22.15) | 0.001 |
MDC | 0 (0.0–7.26) | 6.80 (0.0–27.95) | 0.002 |
IL-13 | 0 (0.0–2.08) | 1.68 (0.0–3.94) | 0.022 |
Rv0849-13 | Rv2031c-6 | Rv2031c-15 | Rv2693-07 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
LTBI | ATBD | p * | LTBI | ATBD | p * | LTBI | ATBD | p * | LTBI | ATBD | p * | |
EGF | 1.65 (0.0–9.04) | 0 (0.0–22.73) | 0.504 | 1.57 (0.0–6.71) | 7.78 (0.0–28.99) | 0.030 | 1.76 (0.0–10.53) | 2.47 (0.0–20.19) | 0.554 | 0 (0.0–4.95) | 6.17 (0.0–22.15) | 0.001 |
EOTAXIN | 0 (0.0–3.29) | 0 (0.0–2.53) | 0.513 | 0.49 (0.0–3.31) | 0 (0.0–3.29) | 0.362 | 0.74 (0.0–2.6) | 0 (0.0–3.41) | 0.630 | 0.49 (0.0–1.7) | 0 (0.0–3.29) | 0.821 |
FGF-2 | 0.0 (0.0–0.0) | 0 (0.0–1.96) | 0.409 | 0.0 (0.0–0.0) | 0 (0.0–1.75) | 0.682 | 0 (0.0–1.16) | 0 (0.0–2.37) | 0.650 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.984 |
Flt | 0 (0.0–1.21) | 0 (0.0–1.22) | 0.546 | 0 (0.0–0.72) | 0 (0.0–1.56) | 0.307 | 0 (0.0–1.21) | 0 (0.0–1.12) | 0.593 | 0 (0.0–1.02) | 0 (0.0–0.73) | 0.331 |
Fractalkine | 11.77 (0.0–21.35) | 0 (0.0–13.07) | 0.113 | 10.96 (0.0–19.53) | 8.04 (0.0–18.30) | 0.549 | 10.39 (0.0–13.07) | 0 (0.0–13.07) | 0.248 | 11.77 (0.0–19.53) | 0 (0.0–14.27) | 0.081 |
G-CSF | 0 (0.0–2.14) | 0.41 (0.0–0.86) | 0.117 | 0.41 (0.0–2.37) | 0 (0.0–2.14) | 0.170 | 0 (0.0–2.14) | 0 (0.0–1.88) | 0.673 | 0 (0.0–1.89) | 0.0 (0.0–0.0) | 0.072 |
GM-CSF | 0.2 (0.0–0.92) | 0.12 (0.0–1.17) | 0.761 | 0.1 (0.0–1.22) | 0.34 (0.0–1.53) | 0.602 | 0.04 (0.0–0.89) | 0.19 (0.0–1.7) | 0.422 | 0.2 (0.0–1.33) | 0.37 (0.0–1.19) | 0.894 |
GRO | 32.21 (9.47–153.24) | 60.57 (1.08–230.83) | 0.563 | 45.57 (8.05–139.76) | 105.35 (21.05–579.55) | 0.017 | 21.05 (1.52–78.48) | 37.51 (3.05–466.44) | 0.136 | 33.11 (9.28–94.95) | 77.50 (21.21–259.76) | 0.036 |
IFNa2 | 0.54 (0.0–2.05) | 0 (0.0–2.11) | 0.716 | 0 (0.0–1.23) | 0.53 (0.0–2.27) | 0.307 | 0 (0.0–1.23) | 0.27 (0.0–1.94) | 0.599 | 0 (0.0–1.23) | 0 (0.0–1.20) | 0.707 |
IFNg | 0.0 (0.0–0.0) | 0 (0.0–0.23) | 0.262 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.763 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.528 | 0 (0.0–0.37) | 0.0 (0.0–0.0) | 0.166 |
IL-10 | 0 (0.0–12.43) | 2.55 (0.0–16.13) | 0.384 | 1.7 (0.0–17.37) | 2.84 (0.0–13.55) | 0.929 | 1.26 (0.0–13.42) | 0.31 (0.0–12.79) | 0.833 | 2.71 (0.0–18.44) | 2.78 (6.08–61.70) | 0.932 |
IL-12p40 | 0 (0.0–0.84) | 0 (0.0–0.09) | 0.043 | 0 (0.0–1.47) | 0 (0.0–0.70) | 0.123 | 0 (0.0–0.76) | 0 (0.0–0.78) | 0.786 | 0 (0.0–0.63) | 0.0 (0.0–0.0) | 0.425 |
IL-12p70 | 0 (0.0–0.37) | 0 (0.0–0.60) | 0.173 | 0 (0.0–0.48) | 0.21 (0.0–0.96) | 0.050 | 0 (0.0–0.49) | 0.53 (0.0–1.47) | 0.029 | 0 (0.0–0.33) | 0.27 (0.0–1.28) | 0.023 |
IL-13 | 0.63 (0.0–3.11) | 1.42 (0.0–4.22) | 0.428 | 1.04 (0.0–3.14) | 0.39 (0.0–3.25) | 0.348 | 0 (0.0–1.33) | 0.60 (0.0–4.23) | 0.117 | 0 (0.0–2.08) | 1.68 (0.0–3.94) | 0.022 |
IL-15 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 1.000 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 1.000 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 1.000 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.370 |
IL-17 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.849 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.710 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.293 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.442 |
IL-1a | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.071 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.029 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.029 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.006 |
IL-1B | 0.0 (0.0–0.0) | 0 (0.0–0.59) | 0.408 | 0.0 (0.0–0.0) | 0 (0.0–1.34) | 0.121 | 0.0 (0.0–0.0) | 0 (0.0–0.65) | 0.015 | 0.0 (0.0–0.0) | 0 (0.0–0.32) | 0.025 |
IL-1RA | 0.48 (0.0–1.87) | 5.57 (0.0–84.45) | 0.001 | 0.47 (0.0–1.42) | 4.51 (0.0–84.50) | 0.006 | 0.51 (0.0–1.18) | 13.55 (0.26–73.2) | 0.001 | 0.06 (0.0–1.87) | 4.78 (0.0–69.27) | 0.001 |
IL-2 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.426 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.649 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.373 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.937 |
IL-22 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 1.000 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 1.000 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 1.000 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 1.000 |
IL-3 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.265 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 1.000 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 1.000 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 1.000 |
IL-4 | 0 (0.0–6.05) | 3.58 (0.0–8.24) | 0.349 | 0 (0.0–6.05) | 2.47 (0.0–13.55) | 0.129 | 0 (0.0–8.15) | 0.28 (0.0–8.73) | 0.469 | 0.28 (0.0–6.05) | 2.61 (0.0–8.45) | 0.392 |
IL-5 | 0 (0.0–0.05) | 0 (0.0–0.10) | 0.479 | 0 (0.0–0.05) | 0 (0.0–0.08) | 0.435 | 0 (0.0–0.05) | 0 (0.0–0.05) | 0.194 | 0 (0.0–0.05) | 0 (0.0–0.05) | 0.621 |
IL-6 | 0 (0.0–1.1) | 0 (0.0–0.72) | 0.917 | 0 (0.0–3.46) | 0.14 (0.0–4.77) | 0.540 | 0 (0.0–0.57) | 0 (0.0–4.06) | 0.127 | 0 (0.0–1.11) | 0 (0.0–2.02) | 0.950 |
IL-7 | 1.52 (0.0–3.39) | 0.72 (0.0–3.85) | 0.369 | 1.66 (0.0–2.89) | 1.46 (0.0–4.32) | 0.952 | 1 (0.0–2.55) | 0.95 (0.0–3.23) | 0.838 | 1.03 (0.0–1.96) | 1.52 (0.0–3.16) | 0.930 |
IL-8 | 114.04 (30.14–404.76) | 182.12 (16.62–600.10) | 0.396 | 189.6 (26.91–441.22) | 368.65 (92.22–1611.75) | 0.041 | 66.98 (0.0–371.87) | 141.5 (30.32–954.13) | 0.059 | 168.23 (43.61–368.22) | 266.01 (123.42–1031.04) | 0.038 |
IL-9 | 0 (0.0–1.32) | 0.92 (0.0–2.41) | 0.158 | 0.1 (0.0–1.15) | 0.63 (0.0–2.51) | 0.269 | 0 (0.0–1.02) | 0.26 (0.0–1.75) | 0.267 | 0.59 (0.0–1.93) | 0.23 (0.0–2.14) | 0.691 |
IP-10 | 8.72 (0.0–15.01) | 1.09 (0.0–10.60) | 0.054 | 7.65 (1.15–20.67) | 6.39 (0.0–17.13) | 0.193 | 7.97 (0.0–12.31) | 3.44 (0.0–10.50) | 0.114 | 5.8 (0.0–16.68) | 3.58 (0.0–13.96) | 0.300 |
MCP-1 | 46.87 (0.0–408.52) | 361.73 (48.60–1447.92) | 0.003 | 77.6 (0.0–815.13) | 465.28 (11.51–1267.78) | 0.105 | 82.22 (0.0–819.08) | 120.37 (0.0–882.54) | 0.989 | 42.15 (0.0–656.25) | 468.47 (0.0–1689.57) | 0.029 |
MCP-2 | 0.64 (0.0–2.31) | 1.23 (0.0–3.02) | 0.517 | 0.94 (0.0–3.23) | 1.22 (0.0–4.38) | 0.961 | 0.64 (0.0–1.64) | 1.08 (0.0–3.72) | 0.540 | 0.53 (0.0–1.91) | 0.38 (0.0–1.79) | 0.683 |
MCP-3 | 14.93 (3.59–48) | 27.65 (6.29–79.52) | 0.268 | 14.13 (2.23–45.15) | 30.53 (9.46–132.49) | 0.033 | 10.89 (0.0–43.31) | 26.33 (8.84–52.16) | 0.078 | 12.92 (0.0–40.57) | 28.2 (6.08–61.70) | 0.079 |
MDC | 9.66 (0.0–38.23) | 9.35 (0.0–54.15) | 0.474 | 5.48 (0.0–36.56) | 20.46 (2.31–48.27) | 0.091 | 2.68 (0.0–25.66) | 7.05 (0.0–25.16) | 0.512 | 0 (0.0–7.26) | 6.80 (0.0–27.95) | 0.002 |
MIP-1a | 0.91 (0.0–11.17) | 1 (0.0–12.01) | 0.843 | 4.56 (0.0–12.92) | 11.42 (0.0–27.52) | 0.663 | 0 (0.0–3.85) | 1.03 (0.0–11.36) | 0.105 | 0 (0.0–3.09) | 0 (0.0–6.49) | 0.302 |
MIP-1B | 0.71 (0.0–8.36) | | | 0.965 | 7.09 (0.0–13.81) | 8.99 (0.0–18.61) | 0.547 | 0 (0.0–4.74) | 0 (0.0–7.98) | 0.502 | 0 (0.0–3.64) | 0 (0.0–7.52) | 0.621 |
sCD40L | 3.305 (0.0–6.54) | 3.71 (0.0–13.14) | 0.386 | 2.48 (0.0–4.19) | 2.94 (0.0–13.81) | 0.242 | 1.45 (0.0–4.63) | 2.52 (0.0–9.94) | 0.355 | 0.78 (0.0–3.49) | 2.88 (0.0–10.37) | 0.141 |
TGF a | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.113 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.113 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.113 | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.113 |
TNF B | 0.06 (0.0–0.12) | 0.06 (0.0–0.12) | 0.696 | 0 (0.0–0.06) | 0.06 (0.0–0.13) | 0.064 | 0 (0.0–0.06) | 0.06 (0.0–0.13) | 0.029 | 0 (0.0–0.06) | 0 (0.0–0.12) | 0.361 |
TNFa | 0.6 (0.0–4.28) | 0.33 (0.0–4.01) | 0.986 | 1 (0.0–3.61) | 1.04 (0.0–3.50) | 0.681 | 0 (0.0–1.65) | 0.06 (0.0–1.87) | 0.453 | 0.84 (0.0–4.42) | 0.04 (0.0–2.23) | 0.290 |
VEGF | 1.48 (0.0–4.26) | 0.33 (0.0–6.45) | 0.795 | 0 (0.0–4.78) | 0.88 (0.0–7.52) | 0.345 | 1.14 (0.0–4.86) | 0 (0.0–5.75) | 0.764 | 1.33 (0.0–4.49) | 1.02 (0.0–6.07) | 0.857 |
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Sanchez, C.; Jaramillo-Valverde, L.; Capristano, S.; Solis, G.; Soto, A.; Valdivia-Silva, J.; Poterico, J.A.; Guio, H. Antigen-Induced IL-1RA Production Discriminates Active and Latent Tuberculosis Infection. Microorganisms 2023, 11, 1385. https://doi.org/10.3390/microorganisms11061385
Sanchez C, Jaramillo-Valverde L, Capristano S, Solis G, Soto A, Valdivia-Silva J, Poterico JA, Guio H. Antigen-Induced IL-1RA Production Discriminates Active and Latent Tuberculosis Infection. Microorganisms. 2023; 11(6):1385. https://doi.org/10.3390/microorganisms11061385
Chicago/Turabian StyleSanchez, Cesar, Luis Jaramillo-Valverde, Silvia Capristano, Gilmer Solis, Alonso Soto, Julio Valdivia-Silva, Julio A. Poterico, and Heinner Guio. 2023. "Antigen-Induced IL-1RA Production Discriminates Active and Latent Tuberculosis Infection" Microorganisms 11, no. 6: 1385. https://doi.org/10.3390/microorganisms11061385
APA StyleSanchez, C., Jaramillo-Valverde, L., Capristano, S., Solis, G., Soto, A., Valdivia-Silva, J., Poterico, J. A., & Guio, H. (2023). Antigen-Induced IL-1RA Production Discriminates Active and Latent Tuberculosis Infection. Microorganisms, 11(6), 1385. https://doi.org/10.3390/microorganisms11061385