Background/Purpose: Enthesitis related arthritis (ERA) is a chronic immune-inflammatory disease with unknown etiology. HLA-B27 is the strongest risk factor predisposing to ERA similar to Spondylarthritis (SpA). Children with HLA-B27 have a more severe disease course and are more likely to have uveitis and sacroiliitis.  In adult SpA, HLA-B27 has been associated with defective bacterial handling, UPR and inflammasome activation in monocytes.  However, no data is available in ERA thus, we studied monocytes in patients with ERA.

Methods: Patients with ERA (ILAR classification) and healthy controls (HCs) were enrolled in the study after informed consent. HLA-B27 was done by PCR. Using flow cytometry monocytes subsets were studied using anti-CD14 and anti-CD16 antibodies, superoxide (ROS) production was measured by Dihydrorhodamine 123 assay while Phagocytosis was measured using pH rhodo Green E. coli Bioparticle Conjugate. Cytokine production by the monocytes after LPS (10ng/ml) stimulation was measured by ELISA.  

Results: 60 HLA-B27 positive, 13 HLA-B27 negative and 19 HLA-B27 negative HCs were included. Clinical features were similar in both HLA-B27 positive and negative ERA patients except the family history which was only present in HLA-B27 positive patients (p< 0.05). JSpADA Score and ESR were higher in HLA-B27 positive patients compared to B27 negative patients (Table 1).

The frequency of Classical Monocytes was higher in B27 positive patients compared to B27 negative patients and B27 negative HCs (p< 0.05; Figure 1a). Monocytes of B27 positive patients produced more superoxide compared to B27 negative HCs (7.180 vs 2.965, p< 0.0001; Figure 1b). Phagocytic Index was higher in B27 positive patients compared to B27 negative patients and HCs (3.390 vs 1.70, p< 0.05; 3.39 vs 1.72, p< 0.05; Figure 1c). TNF- α production was higher at baseline in B27 positive patients compared to B27 negative patients and also on LPS stimulation (8.22 pg/ml vs 0.4035 pg/ml, p< 0.05; 993.7pg/ml vs 343.4pg/ml, p< 0.01; Fig 1d). IL-6 production showed a trend towards increased production in B27 positive patients compared to B27 negative patients.

Conclusion: HLA B27 positive patient’s monocytes were more pro-inflammatory with higher ROS production, increased phagocytosis, and TNF– α production thus may result in persistent inflammation and more severe disease in HLA B27 group.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/monocytes-from-hla-b27-positive-enthesitis-related-arthritis-patients-are-more-activated-than-hla-b27-negative-patients/