Background/Purpose:  While autoantibodies production and immune complex deposition are cornered as hallmark features of systemic lupus erythematosus (SLE), there is growing evidence to propose the pathogenic role of cytokines in this disease. The aim of this follow-up study was to evaluate the sera levels of Th1 cytokines and Th2 in SLE patients, associating these cytokines with disease activity, clinical and laboratory manifestations and also, to assess Th1 and Th2 cytokines levels could be potential biomarkers.

Methods:  Consecutive SLE patients followed at the Rheumatology unit of the State University of Campinas were enrolled in this follow-up study. Healthy volunteers, matched by age and sex, were included as control group. A complete clinical, laboratory and neurological evaluation was performed in all subjects. Neurological manifestations were analyzed according to the ACR classification criteria. SLE patients were further assessed for clinical and laboratory SLE manifestations, disease activity [SLE Disease Activity Index (SLEDAI)], damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)] and long-term therapy. Clinical, laboratory evaluation and blood withdrawal was performed every 4 months for 1 year. Sera for stored. Sera cytokines levels were performed by enzyme linked immunosorbent assay (ELISA) at the end of the study. Data were compared by non-parametric tests.

Results:  Two hundred and eighteen (210 women) SLE patients, with a mean age of 42.62 ±11.98 years were included. The control group, matched by age and sex, consisted of 46 (40 women) healthy volunteers with a mean age of 40.04±13.54 years. Only IL-6 remained significantly increased in SLE patients [median sera levels (pg/mL): T₀ 2.13; T₁ 1.96; T₂ 2.52; T₃ 2.37] compared to healthy controls [T₀ 0.91 (p<0.001); T₁ 0.91 (p<0.001); T₂ 0.93 (p<0.001); T₃ 1.3 (p=0.042)] over time. Sera IL-10 levels correlated with disease activity in all evaluations (T₀ r=0.28 p<0.001; T₁ r=0.23 p=0.001; T₂ r=0.19 p=0.007 T₃ r=0.14 p=0.049). We also observed an association between sera IL-10 levels and nephritis in all evaluations (T₀ p=0.008; T₁ p=0.036; T₂ p=0.024 and T₃ p=0.005). In the paired analyses, significant variation in IFN-γ [median sera levels (pg/mL): T₀ 25.7; T₁ 31.22; T₂ 35.98; T₃ 26.3; p=0.026), IL-12 (T₀ 1.86; T₁ 0.94; T₂ 1.09; T₃ 1.34; p<0.001), IL-4 (T₀ 0.41; T₁ 0.34; T₂ 0.34; T₃ 0.5; p=0.001) and IL-10 (T₀ 0.98; T₁ 0.94; T₂ 1.09; T₃ 1.34; p<0.001) was observed. There was no significant variation in TNF-α (T₀ 2.84; T₁ 2.67; T₂ 2.83; T₃ 2.71; p=0.304) and IL-6 (T₀ 2.13; T₁ 1.96; T₂ 2.52; T₃ 2.37; p=0.241). In the paired analyses, we also observed an association between INF-γ (p=0.039) and IL-10 (p<0.001) and neuropsychiatric manifestations in SLE patients.

Conclusion: IL-10 may be considered a biomarker for disease activity and nephritis in SLE. IFN-γ and IL-10 may identify patients with CNS involvement. Identifying new SLE biomarkers might be a useful tool to sub-classify patients and predict which clinical manifestation these patients might develop.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/longitudinal-analysis-of-th1-and-th2-cytokines-in-systemic-lupus-erythematosus/