Session Information
Date: Monday, October 22, 2018
Title: Systemic Lupus Erythematosus – Etiology and Pathogenesis Poster II
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Low or no alcohol intake (0-5 gm/day or <0.5 drinks/day) has been associated with increased SLE risk among women. Several cytokines and chemokines are involved in disease pathogenesis and are upregulated prior to SLE onset. We investigated whether alcohol intake was associated with B-lymphocyte stimulator (BLyS), stem cell factor (SCF), interferon alpha (IFN-α) and interferon-gamma induced protein (IP-10) concentrations in a large cross-sectional study of women.
Methods: The Nurses’ Health Study (NHS, n=121,700 and NHSII n=116,429) cohorts began in 1976 and 1989, collecting exposure and outcome data on detailed biennial questionnaires. In 1988-1989, ~25% participants donated a blood sample. Cumulative average intake of beer, wine or liquor in drinks per day was assessed prior to the blood draw. We identified 1177 women without SLE prior to blood draw with banked plasma samples and alcohol data. Samples were tested by ELISA assays for BlyS, SCF, IFN-α and IP-10 (each passed quality control [QC] using blinded split samples). We adjusted for inter-batch variation using common QC samples and natural log-transformed all biomarkers to improve normality. ANA (hep2 IF) and ELISAs for anti-dsDNA and extractable nuclear antigens (ENAs; anti-Ro, anti-La, anti-Sm and anti-RNP) were tested. We assessed relationships between alcohol intake (0-5 [low] vs. >5 [high] grams/day) and biomarker concentrations overall and among women with SLE autoantibody positivity in age-adjusted and then multivariable models adjusting for age, race, body mass index, smoking status, and history of depression. SCF and BLyS were assessed using general linear regression, and IP-10 and IFN-α were assessed using Tobit regression due to the high proportion below threshold (IP-10 undetectable=165 [14%] and IFN-α undetectable= 754 [64%]).
Results: Mean age at blood draw was 56 years (SD 10). Low alcohol intake was associated with increased circulating SCF concentration among all women (β [SE]= 0.10 [0.02], p<0.0001) and among the 295 ANA, dsDNA or ENA positive women (β [SE]=0.11[0.04], p=0.05). (Table) In age-adjusted models, BLyS and IP-10 were higher (BLyS β [SE]= 0.05[0.02], p=0.03; IP-10 β [SE]= 2.04 [0.51], p=<0.0001) among women with low alcohol intake, while IFN-α concentration was lower (β [SE]=-5.9 [2.3]; p=0.01).
Conclusion: Low or no alcohol intake was associated with increased SCF concentrations, but not with other SLE-related cytokine/chemokine concentrations in this cross-sectional sample of women without SLE in the NHS and NHSII cohorts. Stem cell factor (SCF) plays a role in T-cell differentiation and hematopoiesis. It is thought to be upregulated prior to SLE diagnosis. Decreased SLE risk among women with moderate alcohol intake may be related to inhibition of SCF.
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Table. A: Mean Daily Alcohol Intake (≤5gm vs. >5 gm) and Continuous Log Concentrations of BLyS and SCF-1 within a cross-sectional sample of women in the Nurses’ Health Study Cohorts |
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Log BLyS |
Log SCF |
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Age-adjusted Models |
Multi-variable Models |
Age-adjusted Models |
Multi-variable Models |
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≤5 gm vs. >5 gm per day Alcohol Intake |
β (SE) |
P |
β (SE) |
P* |
β (SE) |
p |
β (SE) |
P* |
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Among all women (n=1177) |
0.05 (0.02) |
0.03 |
0.04 (0.02) |
0.07 |
0.10 (0.02) |
<0.0001 |
0.08 (0.02) |
0.0001 |
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Among ANA/dsDNA/ENA+ women (n=295) |
0.01 (0.05) |
0.76 |
0.03 (0.05) |
0.50 |
0.11 (0.04) |
0.005 |
0.08 (0.04) |
0.05 |
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Table. B: Mean Daily Alcohol Intake (≤5gm vs. >5 gm) and Continuous Log Concentrations of IP-10 and IFN-α within a cross-sectional sample of women in the Nurses’ Health Study Cohorts |
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Log IP-10** |
Log IFN-α ** |
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Age-adjusted Models |
Multi-variable Models |
Age-adjusted Models |
Multi-variable Models |
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≤5 gm vs. >5 gm per day Alcohol Intake |
β (SE) |
P |
β (SE) |
P* |
β (SE) |
p |
β (SE) |
P* |
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Among all women (n=1177) |
0.03 (0.11) |
0.82 |
0.08 (0.11) |
0.47 |
-0.42 (0.45) |
0.35 |
-0.22 (0.46) |
0.62 |
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Among ANA/dsDNA/ENA+ women (n=295) |
2.04 (0.51) |
<0.0001 |
0.32 (0.22) |
0.14 |
-5.9 (2.3) |
0.01 |
-0.22 (0.95) |
0.82 |
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*Multivariable general linear regression and Tobit models, adjusted for age (continuous), race (Black vs. other), smoking (current/recent quit vs. never or remote quit), body mass index (continuous), history of depression (present vs not) |
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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 Daily Alcohol Intake and SLE-Related Cytokines and Chemokines U.S. Female Nurses without SLE [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/associations-between-daily-alcohol-intake-and-sle-related-cytokines-and-chemokines-u-s-female-nurses-without-sle/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/associations-between-daily-alcohol-intake-and-sle-related-cytokines-and-chemokines-u-s-female-nurses-without-sle/