Differential expression and response to infliximab treatment of specific macrophage subsets in inflammatory synovitis

Background

Myeloid related protein (MRP)8 and MRP14 are expressed in early monocytes, whereas CD163 is marker for mature tissue macrophages.

Objective

To analyse macrophage subsets in RA and SpA, and the effect of infliximab on the synovial infiltration of these subsets.

Methods

Paired synovium and synovial fluid (SF) were collected in 20 RA and 30 SpA patients. In nine SpA patients, synovium was also obtained after 12 weeks of infliximab treatment. The levels of expression of MRP8, MRP14, CD163 and CD68 were analyzed by immunohistochemistry on frozen sections. Levels of MRP8/MRP14 in SF were determined by ELISA.

Results

In inflammatory arthritis, MRP8, MRP14, CD163 and CD68 positive cells were abundant in the lining and sublining layer. The expression of CD68 and CD163 exhibited a cellular pattern. The MRP8 and MRP14 expression was characterized by a cellular staining, with in some samples also an extracellular and perivascular pattern. Comparing RA and SpA, CD68-positive macrophages were equally present (lining P = 0.463, sublining P = 0.235), whereas MRP8 expression was higher in the lining of RA synovium (P = 0.025) and CD163-positive cells were more prominent in SpA synovium (lining P < 0.001, sublining P = 0.017). No differences for MRP8, MRP14, CD163 or CD68 were seen between the SpA subgroups. Confirming that these markers identify different macrophage subsets, the expression of MRP8 and MRP14 was more reduced after infliximab than CD163 (MRP8: lining P = 0.038, sublining P = 0.023; MRP14: lining P = 0.088, sublining P = 0.036; CD163: lining P = 0.119, sublining P = 0.125). Local secretion of soluble MRP8/MRP14 was evidenced by high SF levels (RA 24 530 ng/ml, SpA 4152 ng/ml), which were higher than in serum (RA 20-fold, SpA 6-fold).

Conclusion

MRP8/MRP14 and CD163 identify different macrophage subsets as evidenced by the differential expression in RA versus SpA, and by the differential effect of infliximab on the synovial expression of these markers