Local production of soluble CD163 in the spondyloarthropathic joint

Objective

We recently described an increase of macrophages expressing the scavenger receptor CD163 in synovium and gut of SpA patients. CD163 is a receptor for haemoglobin–haptoglobin (Hp) complexes with highest affinity for the multimeric 2–2 Hp phenotype. CD163 can be shed from the macrophage membrane as a soluble protein (sCD163), which has been shown to inhibit lymphocyte proliferation in vitro. The present aim is to find out if the increased presence of CD163+ macrophages in SpA is associated with Hp polymorphism and/or local production of sCD163 in the joint.

Methods

CD163⁺ macrophages in synovium and sCD163 in synovial fluid (SF) (normalized for albumin levels) were assessed by immunohistochemistry and ELISA, respectively, in 26 SpA and 23 RA patients. Serum sCD163 was analysed in 100 SpA patients, 23 RA patients, and 20 healthy controls (HCs). Serum sCD163 was reassessed after 12 weeks of treatment with infliximab in 20 SpA patients. Finally, Hp polymorphisms were determined in 130 SpA and 23 RA patients.

Results

The number of CD163⁺ macrophages was increased in both synovial lining (P < 0.001) and sublining (P < 0.001) in SpA patients versus RA patients. Within the SpA group, HLA-B27⁺ patients had higher scores than HLA-B27^- (P = 0.022 and P = 0.016 for lining and sublining, respectively). SF median sCD163 levels were high in both SpA (8.04 mg/l) and RA (8.79 mg/l), and approximately three times higher than the corresponding serum levels. Interestingly, in SpA, sCD163 in SF correlated with that in the synovial lining (r = 0.43, P = 0.034) and in serum (r = 0.33, P = 0.002). Serum sCD163 was increased in SpA (2.2 mg/l) (P = 0.008) and RA (3.0 mg/l) (P < 0.001) versus HCs. In SpA, serum sCD163 correlated weakly with CRP and ESR, but was unaffected by infliximab treatment. Finally, Hp polymorphisms in SpA were characterised by a slight underrepresentation of the 1–1 and overrepresentation of the 2–1 phenotype. Hp polymorphisms were not associated with serum or SF sCD163 levels.

Conclusion

These data confirm an increased presence of CD163⁺ macrophages in the SpA joint and indicate local production of sCD163. The increased levels of sCD163 may contribute to local impairment of T-cell proliferation and activation in SpA.