DISTINCT ALTERATIONS IN LINEAGE COMMITTED PROGENITOR CELLS EXIST IN THE PERIPHERAL-BLOOD OF PATIENTS WITH RHEUMATOID-ARTHRITIS AND PRIMARY SJOGRENS-SYNDROME

Objective. Due to the elevated levels of hematopoietically active cyto kines such as tumor necrosis factor (TNF) and granulocyte macrophage c olon), stimulating factor (GMCSF) in rheumatoid arthritis (RA) serum a nd synovium, the increased bone man ow activity in RA, and the effecti veness of GMCSF in mobilizing progenitor cell release from the bone ma rrow into the periphery, we hypothesized that hematopoietic progenitor s are altered in the peripheral blood (PB) of patients with RA. Method s. Flow cytometry assisted cell surface analysis was employed to compa re the distribution of myeloid (CD34+CD33+), B lymphoid (CD34+CD10+), and erythroid (CD34+CD71+) committed progenitor cell subsets in the PB of healthy controls and patients with RA. Since RA and Sjogren's synd rome (SS) are related autoimmune disorders, primary SS PB was also inv estigated. Results. Only those patients with RA exhibiting clinically active disease (RA-A) demonstrated increases in myeloid and B lymphoid progenitor cell subsets. Growth of RA-A progenitors in cytokines prom oting myelopoiesis (GMCSF, TNF, stem cell factor) produced increased m onocyte and dendritic cell progeny, in support of the flow cytometry d ata. Lineage committed (CD34+CD38+) progenitors were increased in SS P B (p < 0.03). However, these did not correlate with either the myeloid , erythroid, or B lymphoid lineages. Conclusion. Distinct alterations in the distribution of PB progenitors are present in RA and primary SS . Since progenitor cells retain a proliferative capacity, their infilt ration into the synovial/glandular environment may contribute to the a ccumulation of inflammatory cells within these sites. We propose that PB progenitors enter the diseased microenvironment through similar mec hanisms as mature hematopoietic elements.