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Introduction: Giant cell arteritis (GCA) is an inflammatory vasculitis of large and medium-sized vessels in individuals over the age of 50 years. To date, no disease-specific autoantibodies or laboratory biomarkers have been identified. Immunologically, GCA is characterized by a pronounced acute phase response and activation of neutrophils and monocytes. Histopathologically, affected vascular segments show extensive immune cell infiltrates, with monocytes playing a central role in vascular wall destruction. However, it remains unclear whether disease-specific monocyte populations can be detected in the peripheral blood of GCA patients for biomonitoring active disease.

Methods: Circulating monocytes from peripheral blood of newly diagnosed, treatment-naïve GCA patients and age-matched healthy controls were analyzed using single-cell RNA sequencing. To adequately capture potentially underrepresented monocyte subpopulations (e.g., low-frequency non-classical monocytes), we profiled transcriptomes from equivalent cell numbers across all known monocyte subsets. Monocyte surface markers identified through this approach were validated and quantified at the protein level by flow cytometry. In a longitudinal follow-up, single-cell RNA sequencing of monocytes from the same GCA patients was repeated three months after initiation of therapy, at which time patients were in remission, and compared with data obtained during the acute disease phase.

Results: This approach identified a distinct monocyte population within the classical monocyte compartment that was exclusively present in patients with active GCA and absent in age-matched healthy controls. Under treatment, this monocyte population disappeared and was no longer detectable at the three-month follow-up, when all patients had achieved remission. The transcriptional profile of these monocytes indicated potential regulation by sex hormones and an increased responsiveness to GM-CSF (granulocyte–macrophage colony-stimulating factor).

Conclusion: These findings identify a previously unrecognized monocyte population in active, untreated GCA with potential relevance for disease pathogenesis, particularly during the early phase of vascular inflammation. This population represents a promising candidate for the development of diagnostic biomarkers and for disease activity monitoring.