Decreased expression of integrins by hematopoietic cells in patients with rheumatoid arthritis and anemia: relationship with bone marrow cytokine levels.
OBJECTIVE
In order to gain a better insight into the pathogenesis of the anemia of chronic disease (ACD) accompanying rheumatoid arthritis, we analyzed the density of the integrins very late antigen (VLA) 4 and VLA-5 on the surface of erythroblasts from bone marrow in patients with rheumatoid arthritis. We also measured the concentration of interleukin (IL) 3 and tumor necrosis factor (TNF) alpha in bone marrow. Finally, we analyzed the relationship between integrin expression on hematopoietic cells and the degree of anemia and concentration of cytokines in bone marrow in patients with rheumatoid arthritis.


RESULTS
Patients with rheumatoid arthritis who also had ACD were found to have lower hemoglobin levels and higher C-reactive protein and erythrocyte sedimentation rate compared to patients who had rheumatoid arthritis without ACD or osteoarthritis of the hip. The mean bone marrow concentration of IL-3 was elevated in patients with rheumatoid arthritis and ACD compared to those without ACD or patients with osteoarthritis. IL-3 concentration in bone marrow showed a significant negative correlation with VLA-4 and VLA-5 expression on erythroblasts, but only in patients with rheumatoid arthritis and ACD.


CONCLUSIONS
Patients with rheumatoid arthritis and ACD have abnormal erythroblasts (decreased VLA density), possibly through an effect on early stages of erythroblast development. Increased levels of IL-3 and the negative correlation between IL-3 concentration in bone marrow and expression of the integrins VLA-4 and VLA-5 may suggest positive feedback between erythroblasts and IL-3, probably associated with decreased sensitivity of bone marrow erythroblasts to IL-3.
Jaworski
J
J
Department of Connective Tissue Diseases, Institute of Rheumatology, Warsaw, Poland. jaworskij@ir.ids.pl
Maslinski
W
W
Pazdur
J
J
Sliwinska-Stanczyk
P
P
Kaminska-Tchorzewska
E
E
Jung
L
L
Lacki
J K
JK
D000740:Anemia / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001853:Bone Marrow / Q000737:chemistry*; D002908:Chronic Disease; D016207:Cytokines / Q000032:analysis*; D006801:Humans; D039041:Integrin alpha4beta1 / Q000032:analysis*; D039081:Integrin alpha5beta1 / Q000032:analysis*; D007377:Interleukin-3 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D039041:Integrin alpha4beta1; D039081:Integrin alpha5beta1; D007377:Interleukin-3; D014409:Tumor Necrosis Factor-alpha