Enhanced neutrophilic granulopoiesis in rheumatoid arthritis. Involvement of neutrophils in disease progression.

Objective: To investigate enhanced granulopoiesis in bone marrow of patients with rheumatoid arthritis (RA), and the role of neutrophils in RA pathogenesis.
Methods: Aspirated bone marrow cells and peripheral blood leukocytes from patients with RA and non-RA patient controls were analyzed morphologically and by 2 color flow cytometry. Thirteen iliac bones (8 RA, 5 non-RA) were examined by light and transmission electron microscope (TEM).
Results: The percentage of CD15+CD16- cells (immature neutrophils) in RA bone marrow (64.3+/-13.4%, mean +/- SD) increased significantly compared to that of non-RA controls (43.2+/-14.3%), whereas the fraction of CD15+CD]6+ cells (mature neutrophils)was greatly decreased (RA 21.8+/-10.1%; non-RA 38.1+/-8.9%). The absolute number of CD15+CD16- cells also increased markedly in RA bone marrow. The ratio of immature cells to the total granulocytes (% CD15+CD16- to % CD15+) correlated with the Lansbury Index score (R = 0.76, p<0.0001). TEM observations revealed that abundant immature neutrophils adhered closely to the trabeculae of the iliac bone. Margins of trabeculae were mostly irregular, especially in severe RA, and collagenous fibers frequently disappeared in those trabeculae with ragged margins.
Conclusion: In RA bone marrow, immature neutrophils (CD15+CD16-) were markedly increased in number; by contrast, no changes were found for mature cells. Augmented production of immature neutrophils (at the promyelocyte-to-myelocyte stage) might lead to the destruction of collagenous fibers in RA bone trabeculae, as revealed by TEM. Generalized bone destruction in RA might, at least in part, be caused by enhanced production of immature neutrophils.