Comment on: Plasma Pyruvate Kinase M2 as a marker of vascular inflammation in giant cell arteritis: reply

Esen, Idil; Jiemy, William F.; Sleen, Yannick van; Reitsema, Rosanne; Bijzet, Johan; Jong, Daniel M de; Nienhuis, P.H.; Slart, Riemer H. J. A.; Heeringa, Peter; Boots, Annemieke M. H.; Brouwer, Elisabeth

doi:10.1093/rheumatology/keac093

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“…In general, these findings point at an upregulation of genes involved in glucose metabolism and proinflammatory responses, and a downregulation of genes involved in the regulation of immune response. Our group have previously reported on metabolically active APCs in GCA patients which is in line with these findings ( 44 ). Taken together, these findings hint at a shifted balance in APCs of GCA patients toward a dysregulated, proinflammatory phenotype of APCs in GCA patients.…”

Section: Discussionsupporting

confidence: 90%

Aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumatica

et al. 2023

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BackgroundGiant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) are overlapping inflammatory diseases. Antigen-presenting cells (APCs), including monocytes and dendritic cells (DCs), are main contributors to the immunopathology of GCA and PMR. However, little is known about APC phenotypes in the peripheral blood at the time of GCA/PMR diagnosis.MethodsAPCs among peripheral blood mononuclear cells (PBMCs) of treatment-naive GCA and PMR patients were compared to those in age- and sex-matched healthy controls (HCs) using flow cytometry (n=15 in each group). We identified three monocyte subsets, and three DC subsets: plasmacytoid DCs (pDCs), CD141+ conventional DCs (cDC1) and CD1c+ conventional DCs (cDC2). Each of these subsets was analyzed for expression of pattern recognition receptors (TLR2, TLR4), immune checkpoints (CD86, PDL1, CD40) and activation markers (HLA-DR, CD11c).Resultst-SNE plots revealed a differential clustering of APCs between GCA/PMR and HCs. Further analyses showed shifts in monocyte subsets and a lower proportion of the small population of cDC1 cells in GCA/PMR, whereas cDC2 proportions correlated negatively with CRP (r=-0.52). Classical monocytes of GCA/PMR patients show reduced expression of TLR2, HLA-DR, CD11c, which was in contrast to non-classical monocytes that showed higher marker expression. Additionally, single cell RNA sequencing in GCA patients identified a number of differentially expressed genes related to inflammation and metabolism in APCs.ConclusionCirculating non-classical monocytes display an activated phenotype in GCA/PMR patients at diagnosis, whereas classical monocytes show reduced expression of activation markers. Whether these findings reflect APC migration patterns or the effects of long-term inflammation remains to be investigated.

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Section: Discussionsupporting

confidence: 90%