AB1275 EXPLORING NOVEL MACROPHAGE SUBTYPES IN EARLY AND LATE GIANT CELL ARTERITIS IMMUNE MICROENVIRONMENT
Authors: H. S. Albano-Aluquin, J. Malysz, V. Aluquin, N. Olsen
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The manifestations of giant cell arteritis(GCA) are mediated by macrophages thru T-cell activation, interferon-gamma(IG), interleukin-12(IL12) production and vascular remodeling but there are no diagnostic or therapeutic modalities directed at these macrophages. CD163-macrophages are pathogenic in ANCA-vasculitis and lupus nephritis but their role in GCA is unknown. The folate-receptor beta (FRB) is a membrane glycoprotein selectively expressed in GCA macrophages and can be a druggable target for folate/antifolate/folate-conjugated therapeutics. We hypothesized that FRB and CD163 macrophages play key roles in GCA and explored their expression in the vascular microenvironment of early and chronic disease. <h3>Objectives:</h3> To compare the immune microenvironment and novel FRB and CD163 macrophage expression in GCA and controls and between early and chronic disease. <h3>Methods:</h3> Temporal artery biopsies (TABs) from GCA-positive (n=9) and negative controls (n=5) were analyzed for FRB, CD163, CD2, IG and IL12 expression/distribution by immunohistochemistry (IHC). Formalin-fixed paraffin-embedded blocks were processed by standard protocol and incubated with the following primary antibodies: FRB (1:800; placenta for control), CD163 (1:25; placenta for control); CD3 (1:75; spleen for control), IG (1:400; Hodgkin lymphoma for control) and IL-12 (1:75; lung cancer for control). We counted the average number of cells per high-power-field for FRB, CD163 and CD3 and semi-quantitatively assessed IG and IL12 as the percentage of inflammatory cells (1=&lt;25%,2=26 to 50%,3= 51-75%,4=&gt;75%). Values were calculated and compared between (1) GCA (n=9) and controls (n=5) and (2) early and late GCA. The correlation between FRB and CD163 macrophages were determined. Statistical analyses were performed using SAS (SAS Institute, Cary, NC) -Wilcoxon rank-sum test and Spearman rank correlation-with significance set at p &lt;0.05 <h3>Results:</h3> The early GCA group (n=6;1 male;5 females) had TABs within 2-3 weeks of symptoms which included vision loss and tongue gangrene and were on high-dose prednisone. Late GCA (n=3; all females) presented with vision loss and chronic relapsing disease that prompted a second TAB done 2.5 years post-diagnosis and were on low dose prednisone. In GCA, FRB and CD163 expression were restricted to activated macrophages in vascular adventitia/media and in close proximity to T cells. IG was noted in T-cells and macrophages while IL-12 was in endothelial cells/macrophages (Figure 1). As expected, the expression of each component was significantly higher in GCA than controls: FRB (14.0 vs 2.3; p=0.006), CD163 (14.7 vs 1.5; p=0.023), CD3 (79 vs 0; p=0.004), IG (3.0 vs1.0; p=0.005) and IL12 (1.5 vs 0; p=0.003). There was no correlation between FRB and CD163 (r=0.52; p=0.17). FRB macrophages persisted in late GCA (13.3 vs 12.5; p=0.52) along with CD3(113.2 vs 72.5; p=0.16), IG (3 vs 3.2; p=0.9) and IL12 (1.5 vs 1.5; p=0.22) with no statistical difference between the first and second biopsies. In contrast, CD163 expression was significantly reduced in late GCA (18.8 vs 9.5; p=0.038) suggesting that these macrophage biomarker responds to chronic steroid therapy. <h3>Conclusion:</h3> Chronic GCA demonstrated persistent FRB macrophages which can predict a relapsing trajectory and serve as novel targets for selective drug therapy. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>