Figures
- Figure 1–
Schema used for classification of disease course among recruited sarcoidosis subjects. ATS: American Thoracic Society; PFT: pulmonary function testing; FVC: forced vital capacity; DLCO: diffusing capacity of the lung for carbon monoxide; IS: immunosuppression; TNF: tumour necrosis factor. #: 34 out of 45 nonprogressive subjects had never received IS or had IS tapered off within 2 years of diagnosis and 11 nonprogressive subjects were maintained on IS from diagnosis; ¶: 16 out of 46 chronic subjects had progressive declines in pulmonary function testing and 30 chronic subjects developed a sarcoidosis flare requiring escalation of IS (organ manifestations of flare: nine pulmonary, seven cutaneous, five neurological, four ocular, three cardiac and two hypercalcaemia).
- Figure 2–
Receiver operating characteristic curve analyses of discrimination between chronic and nonprogressive disease (n=91). Logistic regression-based prediction probabilities using CXCL9, T-cell receptor (TCR) and interferon (IFN) factors outperform lymphopenia, with the difference in area under curve (AUC) being associated with p=0.001.
- Figure 3–
Sarcoidosis subjects with high CXCL9 factor at enrolment more rapidly develop significant declines in pulmonary function or a sarcoidosis flare requiring escalation in immunosuppression during follow-up (p=0.009 by log-rank test). PFT: pulmonary function testing.
- Figure 4–
a) Longitudinal analysis demonstrates a persistent elevation of interferon factor (three-gene mean of STAT1, STAT2 and GBP1) in nonprogressive and chronic sarcoidosis compared with healthy controls. b) Longitudinal analysis reveals a suppression of T-cell receptor (TCR) factor (three-gene mean of CD28, ITK and LEF1) in nonprogressive and chronic sarcoidosis compared with healthy controls, and lower TCR factor in chronic subjects compared with nonprogressive subjects. c) CXCL9 expression remains persistently high among subjects with chronic sarcoidosis compared with both healthy control and nonprogressive sarcoidosis subjects. Mean values are presented; errors bars represent the standard error of the mean. Numbers of PAXgene samples processed at time of quantitative PCR analysis (V1: baseline visit; V2: 6-month visit; V3: 12-month visit) to generate data were as follows. Nonprogressive: V1, n=45; V2, n=27; V3, n=27; chronic: V1, n=46; V2, n=31; V3, n=27; healthy: V1, n=62; V2, n=40; V3, n=36. ns: nonsignificant. #: p=0.005. ***: p<0.001.
Tables
- Table 1– Genes selected for quantitative PCR analysis in longitudinal cohort
Rationale for inclusion in study Genes# n Gene names Implicated in sarcoidosis inflammation 11 ICAM1, IFNG, IL15, IL17, IL6, CXCL9, CXCL10, TNFA, HGF, IL13, TNFSF13B Implicated in granulomatous inflammation 7 IL15RA, IL18R1, IL4, STAT6, B7H1, IL25, SAA4 Invoked in Ingenuity Pathway Analysis 16 IRF1, ITK, JAK2, TYK2, LEF1, MYD88, TLR2, TLR4, TLR8, CTL4A, CD28, TAP1, IRF7, IRF9, STAT1, STAT2 Differentially expressed in sarcoidosis derivation cohort but unknown role in disease 11 LRP1, PLAUR, TBXAS1, GBP1, GBP2, SKIL, CETP, USP15, PIK3AP1, TNFAIP2, LPCAT2 Housekeeping genes 3 RPL13A, B2M, ACTB #: 48 genes in total.
- Table 2– Baseline cohort characteristics
Control Sarcoidosis p-value Subjects n 62 103 Female n (%) 35 (56) 64 (62) 0.51 Age years 42.13±14.55 50.88±10.31 <0.01 Follow-up period months 31±11.4 Race African-American 6 (10) 12 (12) 0.80 White 42 (68) 77 (75) 0.37 Other 14 (22) 14 (13) 0.14 Ethnicity Latino 8 (13) 8 (8) 0.29 Lymphocyte count ×109 cells·L−1 1.81±0.50 1.47±1.79 0.16 Data are presented as n (%) or mean±sd, unless otherwise stated.
- Table 3– Sarcoidosis baseline characteristics by clinical course
Nonprogressive Chronic p-value Subjects 45 46 Age years 49.2±10.2 52.8±10.6 0.11 Range (33–74) (30–76) Females 26 (58) 31 (67) 0.39 Time from diagnosis to enrolment years 2.87±3.9 8.01±9.06 <0.01 Race African-American 5 7 0.76 White 35 31 0.35 Other 5 8 0.55 Ethnicity Latino 2 5 0.43 Scadding stage 0/I/II/III/IV 4/6/20/6/9 5/2/22/5/12 0.64 Lymphocyte count ×109 cells·L−1 1.24±0.5 1.32±1.1 0.64 Systemic immunosuppression at enrolment 14 (31) 30 (65) <0.01 Pulmonary function testing % predicted FVC 102.4±12.5 91.2±16.7 <0.01 FEV1 97.8±16.8 86.7±18.8 <0.01 DLCO 89.8±18.1# 73.4±20.2¶ <0.01 Data are presented as n, mean±sd or n (%), unless otherwise stated. FVC: forced vital capacity; FEV1: forced expiratory volume in 1 s; DLCO: diffusing capacity of the lung for carbon monoxide. #: n=31; ¶: n=26.
Supplementary material
Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.
Files in this Data Supplement:
- Supplementary figures - Figures E1-E6
- Supplementary methods - qPCR normalisation
- Supplementary table - Table E1
