Serum protein profiling reveals distinct patient clusters in giant cell arteritis.

Objectives: We investigated the potential of serum proteins for distinguishing clinical and molecular subtypes in patients with GCA.

Methods: Proximity extension assays were used to analyse 1463 proteins in serum samples from patients with new-onset GCA (n = 16) and patients who have achieved remission (n = 13). Unsupervised and supervised cluster analyses were performed.

Results: Unsupervised cluster analysis identified three distinct clusters based on the protein signature. Compared with cluster 2, patients of cluster 1 had fewer PMR symptoms, increased levels of macrophage migration inhibitory factor (MIF) and pronounced NF-κB, STAT5 and IL-1 signalling. The changes in serum proteins upon remission differed between cluster 1 and 2.Patients with cranial GCA were characterized by altered endothelial and Th17 signalling, whereas patients not responding to treatment within the GUSTO-trial showed increased Th1 and diminished B cell signalling. Patients with anterior ischaemic optic neuropathy displayed higher levels of CHI3L1 (YKL40) and MMP12, and reduced levels of TIMP3.

Conclusion: Protein profiling identified patient clusters in GCA with distinct proteomic features and therefore likely different pathophysiology. These unique proteomic footprints might lead to more targeted treatments in future.