Background/Purpose:

Evidence supports the existence of different sub-phenotypes and the pivotal role of cytokines and autoantibodies in systemic lupus erythematosus (SLE). Cytokines interact in a highly complex network. Thus, understanding how these complex non-linear processes are connected and observed in real-life settings is a major challenge. Cluster approaches may assist in the identification of these sub-phenotypes, which represent such a phenomenon and may contribute to the development of personalized medicine. Therefore, we analyzed the relationship between autoantibodies and cytokine clusters in SLE.

Methods:  

This was an exploratory study in which 70 consecutive women with established SLE (ACR 1997) were assessed. Clinical characteristics, including disease activity (by SLAQ), a 14-autoantibody profile (by IFI and ELISA), and a panel of 15 serum cytokines (by cytometric bead array) were measured simultaneously. Mixed-cluster methodology was used to define autoantibody and cytokine clusters. Bivariate and multivariate analyses, including a heteroscedastic regression model, were done to identify associations between clusters and related variables.

Results:

Three clusters of autoantibodies were defined (Figure 1): neutral, 2) aPL-dominant, and 3) ENA-dominant. Eight cytokines disclosed levels above the threshold (as compared to healthy controls), allowing to find 4 clusters (Figure 2): 1) neutral, 2) chemotactic, 3) IL-6/G-CSF dominant, and 4) IFNα /Pro-inflammatory. Further, the disease activity was associated with cytokine clusters (Figure 3A), which, in turn, were associated with autoantibody clusters (Figure 3B).

Conclusion:

These results support the existence of SLE cytokine-driven sub-phenotypes. They provide insight for a new taxonomy, encourage the practice of personalized medicine, and support proof-of-principle studies.

Figure 1. Autoantibody clusters.

Figure 2. Cytokine clusters.

Figure 3.

A.      Disease activity by cytokine cluster.

B.      Cytokine and autoantibody clusters interaction.