Smoking may drive risk for lupus progression among ANA-positive women
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Higher B-lymphocyte stimulator and low interleukin-10 levels among cigarette smokers, particularly women who are positive for antinuclear antibodies, are associated with an increased risk for systemic lupus erythematosus, researchers noted.
“The cytokines interferon-gamma-induced protein 10 (IP-10) and B-lymphocyte stimulator (BLyS) are upregulated prior to SLE classification and are hypothesized to be involved in the etiology of SLE,” Jill Hahn, MS, ScD, of Brigham and Women’s Hospital, Harvard Medical School, and colleagues wrote. “A recent case-control study suggested that elevated levels of BLyS, stem cell factor (SCF), and type I interferons (including IFN-alpha) in ANA+ individuals might predict progression from asymptomatic autoimmunity to clinical SLE.”
“Cigarette smoking causes chronic inflammation and has been reported to influence production of several inflammatory cytokines and chemokines,” they added. “Thus, smoking may increase SLE risk through effects on SLE-related cytokines/chemokines.”
To determine whether smoking among women was positively associated with SLE-linked pro-inflammatory chemokines and cytokines, or negatively associated with anti-inflammatory cytokine IL-10, Hahn and colleagues analyzed data from the Nurses’ Health Study (NHS). According to the researchers the NHS and the NHS II are prospective cohorts of women who are registered nurses, followed biennially. Established in 1976, the NHS enrolled 121,700 nurses aged 30 years to 55 years in 11 large U.S. states. NHS II, started in 1989, enrolled 116,670 nurses aged 25 years to 42 years in 14 states. Both groups are more than 90% white. About 25% donated blood samples.
For their study, Hahn and colleagues identified 1,177 participants without SLE with banked blood samples that were tested for chemokines and cytokines, as well as antiSm, Ro/SSA, La/SSB and RNP. Antinuclear antibodies were assessed using HEp2 cell indirect immunofluorescence and anti-double-stranded DNA antibodies, and assayed using ELISA. Smoking data were assessed up until blood was drawn. The researchers used separate tobit and linear regression analyses, adjusted for potential confounders, to model associations between smoking and log-transformed chemokine and cytokine concentrations. These analyses were stratified based on autoantibody status.
According to the researchers, B-lymphocyte stimulator levels were 8.7% higher (P < .01) among the 15% current or recent smokers, compared with the 85% past or never smokers. Meanwhile, B-lymphocyte stimulator levels were 24% higher (P < .0001) among those positive for antinuclear antibodies. Current or recent smokers demonstrated IL10 concentrations 46% lower (P < .01) than past or never smokers. Each 10 pack-years of smoking was associated with –17% IL10 (P < .001). Smoking was not associated with interferon-inducible protein10 or stem cell factor.
“Our findings that current/recent smoking was associated with higher BLyS concentrations, particularly in ANA-positive women, that IL-10 was decreased in current/recent smokers, and that IFN-alpha is dramatically elevated among current smokers who had self-reported a [connective tissue disease (CTD)] (the majority of whom were confirmed to have CTDs or CTD symptoms), suggests that current or recent smoking may increase risk of SLE through its effects on these SLE-related cytokines,” Hahn and colleagues wrote.
“The next step is to verify that the observed effect of smoking on SLE is mediated by these biomarkers,” they added. “For now, these results reinforce the importance of counseling women at risk of CTD to avoid smoking.”
Perspective
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David A. McLain, MD, FACP, FACR
Smoking has profound influences on the human immune system and rheumatic disease. We know that smoking is linked to the development of rheumatoid arthritis, particularly among more than 20-year smokers and men. Smokers have been found to have more seropositive disease, more severe disease, and appear to be less likely to experience remission.
Smoking has been associated with an increased risk of SLE, cutaneous LE, and the development of anti-ds DNA antibodies. Studies on the effects of smoking on the immune system include creation of synergism with the shared epitope to markedly increase the risk of RA, induction of apoptosis, alteration of cytokine and hormonal balance, promoting self-antigen immunogenesis and impacting lymphocyte function.
The present study looked specifically at the association of smoking with SLE-related cytokines and chemokines. Researchers used the Nurses’ Health Study (NHS) and the NHSII databases and the banked blood samples drawn with the study. They found that BLyS levels were higher among smokers while IL-10 levels were lower, which may play a role in SLE pathogenesis. Going forward, the role of smoking in autoimmune disease continues to be of interest.
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