Background/Purpose:

Cytokines and autoantibodies are involved in the pathogenesis of systemic lupus erythematosus (SLE). The presence of autoantibodies preceding disease onset by years has been reported both in patients with SLE and in other rheumatic diseases, and changes in cytokine levels have been shown before disease onset in rheumatoid arthritis. The cytokine group interferons and interferon-related molecules are considered to be of importance in SLE pathogenesis. Therefore, we intended to measure cytokine levels, and relate them to autoantibodies, in a northern European population before the onset of symptoms of SLE.

Methods:

The register of patients fulfilling the American College of Rheumatology criteria for SLE and with a given date of the onset of symptoms was coanalysed with the register of the Medical Biobank, Umeå, Sweden. Thirty-six patients were identified as having donated blood samples prior to symptom onset. A nested case-control study (1:4) was performed with 144 age- and sex-matched controls identified from the Medical Biobank register (Umeå, Sweden). The cytokines interferon alpha (IFN)-α, interleukin (IL)-4, IL-9, IL-10, interferon inducible protein 10 (CXCL10/IP-10) and monocyte chemotactic protein-1 (CCL2/MCP-1), were analysed before and after onset of symptoms of SLE using a multiplex kit from Millipore on a Bio-Plex Array Reader (Luminex²⁰⁰). The associations of these cytokines to autoantibodies (ANA, ENA, anti-dsDNA och anti-histone antibodies), from the same blood samples, before disease onset was estimated.

Results:

The IP-10 levels were significantly higher in the individuals who later developed SLE (“prepatients”) than in the controls (median value ±IQR) 372pg/mL±293 versus 253pg/mL±192. IFN-α and IP-10 were strongly correlated (p<0.01) and IP-10 had the most obvious association to autoantibodies, being significantly higher in ANA, SSA and Jo-1 positive individuals (p=0.03, 0.01 and 0.03, respectively) and also to autoantibody positivity over all (p<0.001).  MCP-1 was related to SSA and SSB positivity (p=0.009 and 0.047) and with antibody positivity over all (p=0.015), IFN-α with anti-SSB and antibody positivity over all (p=0.027 and 0.025), IL-4 to anti-dsDNA (p=0.019) and IL-10 to anti-RNP positivity (p=0.041). IL-10, IP-10 and MCP-1 increased significantly between the pre-patient sample, 7.44 pg/mL ±8.93, 372 pg/mL± 293 and 278pg/mL ± 475 respectively, and after SLE was diagnosed,  12.3 pg/mL±20.1, 666 pg/mL± 602  and 1098 pg/mL± 765, respectively (p=0.029, <0.0001 and <0.0001 respectively). The cytokines showed no significant changes in relation to time before disease onset or to the debut SLE-symptom.

Conclusion:

IP-10, MCP-1 and IFN-α had the clearest relationships with autoantibody formation before disease onset of SLE. Since IFNs and IP-10 were strongly correlated with each other these findings support previous theories that the IFN-system is important in the early SLE pathogenesis and autoantibody formation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cytokines-and-their-relation-to-autoantibodies-before-disease-onset-in-systemic-lupus-erythematosus/