Distinct alterations in lineage committed progenitor cells exist in the peripheral blood of patients with rheumatoid arthritis and primary Sjogren's syndrome.
OBJECTIVE
Due to the elevated levels of hematopoietically active cytokines such as tumor necrosis factor (TNF) and granulocyte macrophage colony stimulating factor (GMCSF) in rheumatoid arthritis (RA) serum and synovium, the increased bone marrow activity in RA, and the effectiveness of GMCSF in mobilizing progenitor cell release from the bone marrow into the periphery, we hypothesized that hematopoietic progenitors are altered in the peripheral blood (PB) of patients with RA.


METHODS
Flow cytometry assisted cell surface analysis was employed to compare 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 syndrome (SS) are related autoimmune disorders, primary SS PB was also investigated.


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 promoting myelopoiesis (GMCSF, TNF, stem cell factor) produced increased monocyte and dendritic cell progeny, in support of the flow cytometry data. Lineage committed (CD34+CD38+) progenitors were increased in SS PB (p <0.03). However, these did not correlate with either the myeloid, erythroid, or B lymphoid lineages.


CONCLUSIONS
Distinct alterations in the distribution of PB progenitors are present in RA and primary SS. Since progenitor cells retain a proliferative capacity, their infiltration into the synovial/glandular environment may contribute to the accumulation of inflammatory cells within these sites. We propose that PB progenitors enter the diseased microenvironment through similar mechanisms as mature hematopoietic elements.
Santiago-Schwarz
F
F
Division of Rheumatology and Allergy, Winthrop University Hospital, Mineola, NY, USA.
Sullivan
C
C
Rappa
D
D
Carsons
S E
SE
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000503:physiopathology; D001853:Bone Marrow / Q000473:pathology / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D003713:Dendritic Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases / Q000032:analysis; D015260:Neprilysin / Q000032:analysis; D011990:Receptors, Transferrin / Q000032:analysis; D063268:Sialic Acid Binding Ig-like Lectin 3; D012859:Sjogren's Syndrome / Q000097:blood* / Q000503:physiopathology; D019089:Stem Cell Factor / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000944:Antigens, Differentiation, B-Lymphocyte; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; C068126:CD71 antigen; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D011990:Receptors, Transferrin; D063268:Sialic Acid Binding Ig-like Lectin 3; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D015260:Neprilysin