Anti-Aminoacyl Transfer-RNA-Synthetases (Anti-tRNA) Autoantibodies Associated with Interstitial Lung Disease: Pulmonary Disease Progression has a Persistent Elevation of the Th17 Cytokine Profile
Abstract
:1. Introduction
2. Material and Methods
2.1. Patients
2.2. Pulmonary Function Tests
2.3. High-Resolution Computed Tomography (HRCT) Evaluation
2.4. Autoantibodies
2.5. Cytokines’ Immunoassays
2.6. Statistical Analysis
3. Results
3.1. Patients Included
3.2. PFTs at Baseline and Follow-Up
3.3. Serum Cytokines Quantification
3.4. Association between Cytokines
4. Discussion
5. Highlights
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variable | n = 39 |
---|---|
Age at baseline, years old. | 51.9 ± 9.87 |
Gender female: male | 28 (71.7%):11 (28.3%) |
Pulmonary symptoms before baseline evaluation | 12 (7–24) months |
Anti-tRNA autoantibody | |
Jo1+ (%) | 10 (25.64) |
PL7+ (%) | 8 (20.51) |
PL12+ (%) | 11 (28.20) |
Ej+ (%) | 10 (25.64) |
Ro52+ (%) | 27 (69.23%) |
HRCT pattern | |
OP | 20 (51.28%) |
NSIP | 17 (43.59%) |
UIP | 2 (5.13%) |
Lung disease extent in HRCT * | 56 (40–62) |
Ground glass extent in HRCT * | 51.52 (34.4–57.04) |
Fibrosis extent in HRCT * | 5.6 (3.72–8.88) |
Baseline % of predicted value of FVC (median, (IQR)) | 50 (41–74) |
Baseline % of the predicted value of the DLCO | 45 (33–66) |
CK level at baseline | 100 (62–384) min, max: 22–6318 |
Arthritis | 28 (72%) |
Fever | 20 (51.28%) |
Mechanic’s hand sign | 23 (60%) |
Raynaud’s phenomenon | 13 (33%) |
Proximal muscle weakness | 28 (72%) |
Modified Borg scale at rest | 4 (2–5) |
Modified Borg scale during activity | 6 (5–9) |
Variable | Patients with ILD Progression n = 3 | Patients without ILD Progression n = 36 | p-Value |
---|---|---|---|
Age at baseline assessment | 52 (49–83) | 51 (45.5–56) | 0.42 |
Female gender | 2 (66.6%) | 34 (94.45%) | 1.0 |
Pulmonary symptoms before baseline evaluation | 12 (12–24) | 10.5 (3.5–20) | 0.33 |
Anti-tRNA autoantibody | |||
Jo1+ | 0 | 10 (27.77%) | |
PL7+ | 1 (33.33%) | 7 (19.44%) | |
PL12+ | 2 (66.66%) | 9 (25%) | |
Ej+ | 0 | 10 (27.77%) | 0.27 |
HRCT pattern | |||
OP | 2 (66.66%) | 18 (50%) | |
NSIP | 1 (33.33%) | 16 (44.44%) | |
UIP | 0 | 2 (5.55%) | 1.0 |
Lung disease extent in HRCT * | 63 (56–70) | 56 (40–62) | 0.34 |
Ground glass extent in HRCT * | 53.2 (50.4–56) | 51.2 (34.4–57) | 0.86 |
Fibrosis extent in HRCT * | 9.8 (5.6–14) | 4.96 (3.72–8.5) | 0.26 |
Baseline % of predicted value of FVC (median, (IQR)) | 66 (36–77) | 49 (41.5–74) | 0.87 |
Baseline % of predicted value of the DLCO | 55 (15–66) | 44.5 (33.5–67) | 0.95 |
CK level at baseline | 42 (22–50) | 105.5 (72.5–516.5) | 0.01 |
Arthritis | 2 | 1 | 1.0 |
Fever | 1 | 2 | 1.0 |
Modified Borg scale at rest | 4 (2.5–5) | 3 (2–3) | 0.21 |
Modified Borg scale during activity | 6.5 (5–5.5) | 5 (4–6) | 0.17 |
Variable | Anti-Jo1+ Patients n = 10 | Anti-PL7+ Patients n = 8 | Anti-PL12+ Patients n = 11 | Anti-EJ+ Patients v10 | p-Value |
---|---|---|---|---|---|
Age at baseline assessment | 45 ± 9.5 | 62 ± 10.7 | 51.5 ± 5.6 | 50.9 ± 7.4 | 0.002 ∃ |
Female gender * | 9 (90%) | 7 (87.5%) | 4 (45.5%) | 9 (90%) | 0.13 |
Pulmonary symptoms before baseline evaluation | 7.5 (2–14) | 15 (5–24) | 12 (1–20) | 12 (6–12) | 0.87 |
Patients with ILD progression at follow-up. | 0 | 1 (12.5%) | 2 (18.18%) | 0 | 0.27 |
Arthritis * | 10 (100%) | 5 (62%) | 8 (73%) | 5 (50%) | 0.06 |
Mechanic’s hand sign * | 8 (80%) | 5 (62.5%) | 7 (63.6%) | 3 (30%) | 0.16 |
Fever * | 7 (70%) | 3 (37.5%) | 4 (36.4%) | 6 (60%) | 0.37 |
Raynaud’s phenomenon * | 6 (60%) | 3 (37.5%) | 2 (19%) | 2 (20%) | 0.18 |
CK level at baseline *** | 516 (107–2413) | 61 (34–75.5) | 100 (50–178) | 240 (88–1652) | 0.004 |
Anti-Ro52 positivity * | 5 (50%) | 5 (62.5%) | 8 (72.7%) | 8 (80%) | 0.55 |
Baseline % of predicted value of FVC ** | 65 (34–76) | 75 (59–86.5) | 45 (42–64) | 44 (40–60) | 0.20 |
Baseline % of predictive value of DLCO | 51 (38–80) | 48 (29.5–61.5) | 40 (33–55) | 45.5 (32–73) | 0.85 |
Patients with improvement in FVC (>10%) or in DLCO (>15%) * | 6 (60%) | 4(50%) | 6 (54.5%) | 10 (100%) | 0.047 |
Patients with lung disease progression in FVC (>10%) or in DLCO (15%) * | 0 | 1 (12.5%) | 2 (19%) | 0 | 0.27 |
Follow-up % of predicted value of FVC | 74 (57–104) | 66 (49–95.5) | 58.5 (43–62) | 71 (43–92) | 0.35 |
Follow-up % of predicted value of DLCO | 80 (55–119) | 70 (37–89) | 56 (40–57) | 61 (35–87) | 0.37 |
Variable | Anti-Jo1+ Patients n: 10 | Anti-PL7+ Patients n: 8 | Anti-PL12+ Patients n: 11 | Anti-EJ+ Patients n: 10 | p-Value | ILD anti tRNA Positive Patients n: 39 |
---|---|---|---|---|---|---|
IL-1β | 92 (75.3–310) | 202 (65–327) | 319 (107–335) | 239 (105–318) | 0.22 | 264 (88–324) |
IL-2 | 262 (236–284) | 280 (214–286) | 278 (273–282) | 279 (272–284) | 0.82 | 278 (247–284) |
IL-4 | 288 (277–624) | 522 (261–761) | 730 (446–786) | 695 (516–744) | 0.09 | 688 (283–758) |
IL-5 | 408 (308–458) | 354 (226–465) | 453 (370–459) | 453 (440–463) | 0.79 | 452 (311–463) |
IL-6 | 445 (423–2243) | 1509 (437–2283) | 2205 (415–2318) | 1996 (440–2324) | 0.67 | 1694 (438–2313) |
IL-9 | 454 (383–495) | 430 (389–524) | 434 (412–480) | 463 (450–565) | 0.71 | 454 (412–495) |
IL-10 | 70 (67–73) | 73 (48–85) | 74 (71–97) | 76 (70–84) | 0.31 | 73 (68–81) |
IL-12 p70 | 321 (287–331) | 317 (289–324) | 302 (290–318) | 305 (279–326) | 0.88 | 311 (287–326) |
IL-13 | 105 (95–124) | 144 (108–189) | 153 (117–167) | 123 (106–190) | 0.21 | 119 (104–174) |
IL-17A | 232 (167–290) | 230 (146–290) | 193 (151–290) | 214 (176–289) | 0.89 | 201 (164–289) |
IL-18 | 908 (795–1408) | 907 (814–1170) | 1065 (1022–1292) | 1037 (966–1441) | 0.23 | 1022 (875–1353) |
IL-21 | 283 (175–379) | 349 (259–505) | 340 (273–358) | 345 (294–564) | 0.64 | 346 (233–450) |
IL-22 | 871 (740–952) | 1026 (730–1064) | 1027 (981–1058) | 1017 (883–1048) | 0.37 | 1017 (824–1058) |
IL-23 | 898 (863–947) | 917 (795–979) | 937 (916–1003) | 932 (903–1259) | 0.28 | 927 (885–976) |
IL-27 | 453 (447–469) * | 474 (458–483) | 474 (464–492) | 483 (264–324) * | 0.02 | 473 (458–485) |
INF-γ | 661 (624–724) | 698 (607–950) | 815 (633–938) | 819 (668–856) | 0.41 | 720 (644–860) |
GM-CSF | 856 (725–856) | 808 (667–856) | 843 (688–856) | 686 (662–856) | 0.77 | 843 (670–856) |
TNF-α | 346 (326–405) | 365 (313–404) | 405 (403–407) | 403 (349–404) | 0.07 | 403 (332–405) |
Variable | Anti-Jo1+ Patients n = 10 | Anti-PL7+ Patients n = 8 | Anti-PL12+ Patients n = 11 | Anti-EJ+ Patients n = 10 | p-Value | ILD anti tRNA Positive Patients n = 39 |
---|---|---|---|---|---|---|
IL-1β | 92 (70–225) | 235 (187–405) | 224 (214–234) | 223 (104–233) | 0.05 * | 264 (88–324) |
IL-2 | 256 (223-272) | 279 (238–479) | 276 (264–561) | 268 (266–273) | 0.19 | 271 (249–288) |
IL-4 | 594 (288–786) | 754 (471–2595) | 691 (660–803) | 709 (528–744) | 0.60 | 698 (472–803) |
IL-5 | 357 (235–445) | 443 (440–1722) | 438 (428–476) | 437 (313–442) | 0.09 | 438 (337–447) |
IL-6 | 650 (435–2308) | 2339 (2127–5185) | 2298 (1709–2349) | 2313 (430–2359) | 0.38 | 2298 (456–2358) |
IL-9 | 441 (357–558) | 512 (3893–1871) | 551 (536–622) | 505 (398–548) | 0.39 | 534 (398–593) |
IL-10 | 64 (61–75) | 129 (73–235) | 69 (66–84) | 72 (68–80) | 0.12 | 71 (63–89) |
IL-12 p70 | 322 (296–328) | 308 (278–435) | 298 (275–351) | 296 (284–342) | 0.90 | 305 (283–344) |
IL-13 | 111 (97–143) | 123 (99–518) | 102 (72–211) | 306 (283–345) | 0.76 | 109 (97–172) |
IL-17A | 279 (220–286) | 288 (152–477) | 225 (140–287) | 125 (124–143) | 0.13 | 225 (126–290) |
IL-18 | 1128 (672–1535) | 1231 (845–2653) | 1108 (1039–1504) | 1050 (831–1260) | 0.82 | 1064 (878–1535) |
IL-21 | 526 (131–959) | 583 (341–4368) | 327 (281–495) | 331 (297–740) | 0.18 | 345 (297–765) |
IL-22 | 1408 (729–2025) | 1298 (1032–2698) | 1058 (786–3174) | 1045 (949–2017) | 0.81 | 1062 (870–2262) |
IL-23 | 923 (900–945) | 1033 (915–3631) | 932 (922–956) | 929 (910–939) | 0.44 | 932 (908–1065) |
IL-27 | 475 (457–489) | 477 (462–1742) | 481 (475–2359) | 481 (470–6790) | 0.60 | 479 (461–1650) |
INF-γ | 786 (631–843) | 1042 (760–1391) | 843 (691–991) | 713 (669–738) | 0.14 | 815 (669–932) |
GM-CSF | 855 (679–856) | 2084 (765–3786) | 710 (691–856) | 716 (689–856) | 0.28 | 855 (689–856) |
TNF-α | 380 (309–407) | 406 (377–1259) | 405 (403–410) | 408 (404–409) | 0.33 | 406 (359–409) |
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Ramos-Martinez, E.; Falfán-Valencia, R.; Pérez-Rubio, G.; Mejia, M.; Buendía-Roldán, I.; González-Pérez, M.I.; Mateos-Toledo, H.N.; Rojas Serrano, J. Anti-Aminoacyl Transfer-RNA-Synthetases (Anti-tRNA) Autoantibodies Associated with Interstitial Lung Disease: Pulmonary Disease Progression has a Persistent Elevation of the Th17 Cytokine Profile. J. Clin. Med. 2020, 9, 1356. https://doi.org/10.3390/jcm9051356
Ramos-Martinez E, Falfán-Valencia R, Pérez-Rubio G, Mejia M, Buendía-Roldán I, González-Pérez MI, Mateos-Toledo HN, Rojas Serrano J. Anti-Aminoacyl Transfer-RNA-Synthetases (Anti-tRNA) Autoantibodies Associated with Interstitial Lung Disease: Pulmonary Disease Progression has a Persistent Elevation of the Th17 Cytokine Profile. Journal of Clinical Medicine. 2020; 9(5):1356. https://doi.org/10.3390/jcm9051356
Chicago/Turabian StyleRamos-Martinez, Espiridión, Ramcés Falfán-Valencia, Gloria Pérez-Rubio, Mayra Mejia, Ivette Buendía-Roldán, Montserrat I. González-Pérez, Heidegger N. Mateos-Toledo, and Jorge Rojas Serrano. 2020. "Anti-Aminoacyl Transfer-RNA-Synthetases (Anti-tRNA) Autoantibodies Associated with Interstitial Lung Disease: Pulmonary Disease Progression has a Persistent Elevation of the Th17 Cytokine Profile" Journal of Clinical Medicine 9, no. 5: 1356. https://doi.org/10.3390/jcm9051356