Session Information
Date: Tuesday, October 23, 2018
Title: Epidemiology and Public Health Poster III: SLE, SSc, APS, PsA, and Other Rheumatic Diseases
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Current cigarette smoking and recent cessation (within 4 years), compared to no smoking or remote cessation, have been associated with increased anti-dsDNA+ SLE risk among women. SLE-specific cytokines and chemokines have been found to be increased prior to diagnosis. We conducted cross-sectional analyses to investigate whether current smoking was associated with concentrations of SLE-associated cytokines including B lymphocyte stimulator (BLyS), stem cell factor (SCF), interferon-inducible protein-10 (IP-10), and interferon-alpha (IFNα) within a general population of women at risk of SLE.
Methods: The Nurses’ Health Study (NHS, n=121,700) and NHSII (n=116,429) cohorts were begun in 1976 and 1989, respectively, and collected detailed exposure and outcome data biennially. In 1988- 1989, ~25% participants donated a blood sample. We identified 1177 women without SLE with banked plasma samples and smoking exposure data prior to the blood draw. We tested for presence of ANA (by Hep2 IF), and anti-dsDNA and extractable nuclear antigens (ENAs; anti-Ro, anti-La, anti-Sm and anti-RNP, by ELISAs]). Samples were tested by ELISA for BLyS, SCF, IP10, and IFNα. Each passed quality control [QC] using blinded split samples. We adjusted for inter-batch variation using common QC samples. Cytokine/chemokine concentrations were natural log-transformed to improve normality. We assessed relationships between smoking and biomarker concentrations using general linear regression for BLyS and SCF. Tobit regression was employed for IP-10 and IFNα due to a high proportion below the threshold of detection (165 [14%] and 754 [64%]).
Results: Mean age at blood draw was 56 (SD 10); 64% of women were White, 36% Black; 15% were current/recent smokers. No association was found between current/recent smoking (vs. never or >4 years past) and ANA/dsDNA/ENA positivity (multivariable-adjusted OR 1.11 [95% CI 0.77, 1.60]). Current/recent smoking was associated with increasing circulating log BLyS (β [SE] =0.10 [0.03], p<0.0001) and log IFNα (β [SE]= 1.15 [0.52], p=0.03), but not SCF or IP-10 compared to never/distant smoking (Table). When restricted to the 295 women with ANA+, dsDNA+ or ENA+, the relationship between current/recent smoking and log BLyS was stronger.
Conclusion: Current smoking was associated with elevated BLyS, but not SCF-1 or IP-10, among women without SLE. BLyS is responsible for B-cell survival and maturation and has been reported to be elevated in the lungs of smokers. In stimulating the production of BLyS, smoking may accelerate onset or severity of autoantibody-positive SLE.
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A. General Linear Regression Analyses: NHS and NHSII Current Smoking* vs. Past or Never Smoking and Continuous Concentrations of SLE-Associated Biomarkers, Log BLyS and Log SCF-1 among women without SLE |
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Log BLyS |
Log SCF |
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Age-adjusted β (SE) |
p |
Multivariable-adjusted β (SE)** |
p |
Age- adjusted β (SE) |
p |
Multivariable- adjusted β (SE)** |
p |
|
Current Smoking* among all women (n=1177) |
0.09 (0.03) |
0.0006 |
0.10 (0.03) |
0.0002 |
-0.04 (0.02) |
0.12 |
-0.01 (0.02) |
0.60 |
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Current Smoking* among ANA/dsDNA/ENA+ women (n=295) |
0.19 (0.05) |
0.0003 |
0.21 (0.05) |
< 0.0001 |
-0.09 (0.08) |
0.30 |
-0.09 (0.10) |
0.34 |
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B. Tobit Analyses***: Current Smoking* vs. Past or Never Smoking and Continuous Concentrations of SLE-Associated Biomarkers, IP-10 and Log IFNα |
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Log IP-10 |
Log IFNα |
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Age-adjusted β (SE) |
p |
Multivariable-adjusted β (SE)** |
p |
Age- adjusted β (SE) |
p |
Multivariable- adjusted β (SE)** |
p |
|
Current Smoking* among all women (n=1177) |
0.12 (0.13) |
0.36 |
0.10 (0.13) |
0.43 |
1.37 (0.52) |
0.009 |
1.15 (0.52) |
0.03 |
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Current Smoking* among ANA/dsDNA/ENA+ women (n=295) |
-0.04 (0.24) |
0.88 |
-0.03 (0.25) |
0.91 |
1.98 (1.03) |
0.05 |
1.57 (1.04) |
0.13 |
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*Current smoking: includes those who quit within past 4 years of blood draw as risk of SLE continued to be elevated among recent quitters in past analyses. **Multivariable analyses: adjusted for age, race, body mass index, alcohol intake, history of depression (additional adjustment for oral contraceptive use, menopausal status, postmenopausal hormone use did not affect estimates) *** Tobit analysis is a method that allows for maximum usage of cytokines/chemokines if there are many undetectable values.
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To cite this abstract in AMA style:
Leatherwood C, Liu X, Malspeis S, Roberts A, Sparks JA, Karlson E, Feldman CH, James JA, Kubzansky L, Costenbader K. Associations between Current Cigarette Smoking and SLE-Related Cytokine and Chemokine Biomarkers Among U.S. Female Nurses without SLE [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/associations-between-current-cigarette-smoking-and-sle-related-cytokine-and-chemokine-biomarkers-among-u-s-female-nurses-without-sle/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/associations-between-current-cigarette-smoking-and-sle-related-cytokine-and-chemokine-biomarkers-among-u-s-female-nurses-without-sle/