Impaired bone marrow hematopoietic progenitor cell function in rheumatoid arthritis patients candidated to autologous hematopoietic stem cell transplantation.
We have evaluated bone marrow morphology, percentage of bone marrow CD34(+) cells, proliferative activity of bone marrow precursors, clonogenic assay (BFU-E and CFU-GM) in short-term bone marrow cultures, and bone marrow cell apoptosis, together with serum TNF-alpha and IL-6, in 16 chronic, refractory RA patients, as well as in five healthy controls. Of 16 RA patients (68.7%), 11 showed a reduced bone marrow cellularity, while it was normal in all the controls. In RA patients, the median percentage of CD34(+) bone marrow cells, the median percentage of proliferating bone marrow myeloid precursors, and the median number of both BFU-E and CFU-GM colonies were significantly lower than observed in the controls. As far as TNF-alpha and IL-6 titers is concerned, the latter did not significantly differ from controls' values, while TNF-alpha titers were significantly lower in healthy controls. Finally, the median apoptotic index of early bone marrow myeloid cells of RA patients was significantly higher compared with controls. These observations may identify the biological risk factors for impaired mobilization and/or engraftment when RA patients are candidates for autologous hematopoietic stem cell grafting.
Porta
C
C
Istituto di Medicina Interna ed Oncologia Medica, Università degli Studi di Pavia e I.R.C.C.S. Policlinico San Matteo, Pavia, Italy. c.porta@smatteo.pv.it
Caporali
R
R
Epis
O
O
Ramaioli
I
I
Invernizzi
R
R
Rovati
B
B
Comolli
G
G
Danova
M
M
Montecucco
C
C
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000473:pathology*; D001854:Bone Marrow Cells / Q000473:pathology*; D016022:Case-Control Studies; D002455:Cell Division; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D022423:Myeloid Cells / Q000473:pathology; D018579:Patient Selection; D014182:Transplantation, Autologous; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018952:Antigens, CD34; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha