Disease patterns and tissue cytokine profiles in giant cell arteritis

Abstract

Objective. To determine whether clinical heterogeneity in patients with giant cell arteritis (GCA) is correlated with different patterns in the tissue-specific inflammatory response. Methods. Twenty-three patients with typical histomorphologic findings of GCA were grouped according to the presence or absence of jaw claudication and/or visual abnormalities, fever, concomitant polymyalgia rheumatica (PMR), and histologic evidence of giant cell formation. The inflammatory response in temporal artery biopsy specimens was characterized by semiquantification of cytokine messenger RNA (mRNA) transcripts using reverse transcriptase-polymerase chain reaction, followed by oligonucleotide hybridization with cytokine-specific probes. Clinical patterns were then correlated with profiles of tissue cytokines. Results. Inflammatory cytokines were expressed in all temporal artery tissues. In situ synthesis of interleukin-2 (IL-2), interferon-γ (IFNγ), and IL-1β mRNA, but not of IL-10 and IL-12 mRNA, distinguished different patterns of inflammation, and these patterns correlated with clinical manifestations of the disease. Patients with evidence of ischemic symptoms, indicated by jaw claudication and/or visual symptoms, typically expressed higher concentrations of IFNγ mRNA (P = 0.008) and IL-1β mRNA (P = 0.02). Presence of fever was correlated with lower copy numbers of IFNγ (P = 0.02). Formation of giant cells in the granulomatous infiltrates was associated with the local synthesis of IFNγ mRNA (P = 0.003). Tissue from GCA patients with concomitant PMR contained higher levels of IL-2 mRNA transcripts (P = 0.001). Conclusion. Variations in the clinical presentation of GCA were correlated with cytokine mRNA expression in the affected temporal arteries. Differences in the effector functions of tissue-infiltrating T cells distinguished disease patterns in which either local ischemic symptoms or systemic involvement was dominant, or in which there was co-occurrence of PMR. Definition of different patterns of inflammation in GCA might, therefore, facilitate the design of differentiated therapeutic approaches.