Background/Purpose: Interferon-α (IFN-α) plays a prominent pro-inflammatory role in SLE. Studies suggest clinical/serologic discordance may illuminate SLE pathophysiology: peripheral IFN-α production is blunted in autoantibody-producing, clinically quiescent SLE mice despite abundant IFN-α-producing plasmacytoid dendritic cells (pDCs); continuous pDC stimulation yields reversible blunting of the IFN-α response in vitro.  Thus SACQ patients, who exhibit persistent autoantibody production despite durable clinical quiescence, may provide unique insights.  We thus measured IFN-associated cyto/chemokines 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; 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.  Plasma cyto/chemokines were measured by 65-plex Luminex panel, with the 16 most relevant selected a priori for analysis.  Bonferroni correction was applied. Non-parametric univariate and logistic regression analyses were conducted.  Given the vast range of cyto/chemokine levels, values were transformed by a factor of 10, 100, or 1000, as appropriate, to facilitate interpretation. 

Results: We identified 25, 28 and 48 SACQ, SQCQ and SACA patients, respectively.   IFN-α, IL-6, IL-10, IP-10 and MCP-1 levels were lower in SACQ vs SACA patients (p = 0.006, 0.0018, and <0.0001 (last three), respectively).  There were no differences in cyto/chemokine levels between SACQ and SQCQ patients.  IFN-α and IP-10 were moderately correlated (r=0.79).  Disease duration at study start differed between SACQ and SACA patients (18.5±12.1 vs 7.4±7.3 yrs, p=0.0002) as did the proportion with anti-Ro, -La, and –RNP positivity (84.0 vs 53.6%; 48 vs 32.1%; 40 vs 28.6%, p=0.005, 0.004 and 0.023, respectively).  There were no differences in clinical manifestations from disease onset between SACQ and SACA patients.  Logistic regression revealed that increased levels of IL-10 (OR 7.35 [1.04,51.93]) and MCP-1 (OR 2.33 [1.23,4.41]) were associated with SACA status.  Increased disease duration (OR 1.12 [1.03, 1.23] and anti-Ro positivity (OR 20 [2.38,166.67]) were associated with SACQ status.  When SACA patients with disease duration <6 years were excluded, MCP-1 elevation remained associated with SACA (OR 1.95 [1.28,2.97] and anti-Ro positivity with SACQ (OR 7.14[1.47,33.33].  Regression analysis applied to SACQ vs SQCQ patients similarly revealed anti-Ro positivity was associated with SACQ status (OR 4.55[1.23,16.67]).

Conclusion: IFN-associated cyto/chemokine profiles differed between SACQ and SACA, but not SACQ and SQCQ, patients.  Elevations in MCP-1 and IL-10 were associated with SACA status; there were no cyto/chemokines associated with SACQ status.  These findings warrant further pursuit to determine if they may facilitate clinical prediction.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/interferon-associated-cytokine-and-chemokine-expression-in-patients-with-serologically-active-clinically-quiescent-sacq-systemic-lupus-erythematosus-sle/