Session Type: Abstract Submissions (ACR)
Background/Purpose: Interferon-α (IFN-α) plays a prominent pro-inflammatory role in SLE. Studies suggest clinical/serologic discordance may illuminate systemic lupus erythematosus (SLE) pathophysiology, as peripheral IFN-α production is blunted in some autoantibody-producing, clinically quiescent SLE mice despite abundant IFN-α –producing plasmacytoid dendritic cells (pDCs). This goes against the current SLE paradigm which postulates that nucleic acid-containing immune complexes stimulate pDCs via Toll-like receptors to generate copious IFN-α, leading to upregulation of proinflammatory molecules and clinical disease. Thus serologically active clinically quiescent (SACQ) patients who, like these mice, exhibit persistent autoantibody production despite durable clinical quiescence, may provide unique insights. We investigated whether 5 IFN-associated genes and IFN-associated cyto/chemokines differed in SACQ patients compared to serologically and clinically active (SACA) and serologically and clinically quiescent (SQCQ) patients.
Methods: We defined SACQ and SQCQ as ≥2-year periods without clinical activity, with/without persistent serologic activity, respectively, by SLE Disease Activity Index 2000 (SLEDAI-2K), over which antimalarials were permissible but corticosteroids/immunosuppressives were not. SACA was defined as disease activity, by SLEDAI-2K, which compelled immunosuppression. Clinical and lab data were collected at each visit. Gene expression of OAS1, IFT1, MX1, LY6E and ISG15 was measured by qRTPCR, and a composite IFN gene score was developed. Plasma cyto/chemokines were measured by 65-plex Luminex panel, with the 19 most relevant selected a priorifor analysis. Non-parametric univariate and logistic regression analyses were conducted with Bonferroni correction applied.
Results: Twenty-two, 27 and 43 SACQ, SQCQ and SACA patients, respectively, were included in the analysis. There were no differences in gene expression, or in cyto/chemokine levels between SACQ and SQCQ. SACQ patients were older (43.7 ± 13.7 vs 28.7 ± 9.4, p < 0.0001) and had longer disease duration (18.5 ± 12.5 vs 7.4 ± 7.1 years, p=0.0005) at study start than did SACA patients. Anti-Ro (82% vs 46%, p=0.007) and anti-La (50% vs 13%, p=0.002), antibodies were significantly more prevalent in SACQ than in SACA patients. Anti-RNP antibodies were significantly more prevalent in SACA than in SACQ (74% vs 36%, p=0.004). The SACQ IFN gene score was significantly lower than that of SACA (p=0.003). Levels of GM-CSF, IL-6, IL-10, IP-10, MCP-1 and TNF-α were significantly lower in SACQ than SACA. Logistic regression analysis revealed that anti-La antibody positivity, and low levels of MCP-1 and LY6Ewere associated with SACQ status.
Conclusion: The SACQ interferon signature and cytokine/chemokine profile closely resemble those of patients who are in complete remission. Anti-La antibody positivity and low levels of MCP-1 and LY6E were associated with SACQ status in this small pilot study. The presence of this combination of factors may serve to reinforce the clinical impression of disease quiescence in SACQ patients.
A. J. Steiman,
M. B. Urowitz,
J. E. Wither,
D. D. Gladman,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-interferon-alpha-signature-in-patients-with-serologically-active-clinically-quiescent-systemic-lupus-erythematosus/