Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone marrow erythroid cells: improvement following anti-tumor necrosis factor-alpha antibody therapy Export

@article{citeulike:3401523, abstract = {Circumstantial evidence has implicated tumor necrosis factor [alpha] (TNF-[alpha]) in the pathogenesis of anemia of chronic disease (ACD) in rheumatoid arthritis (RA). We investigated the role of TNF-[alpha] in erythropoiesis of patients with active RA (n = 40) and the effect of anti-TNF-[alpha] antibody administration (cA2). Patients with RA had lower numbers of CD34+/CD71+ and CD36[-]/glycophorin A+ (glycoA+) bone marrow (BM) cells and increased proportions of apoptotic cells within the CD34+/CD71+ and CD36+/glycoA+ cell compartments, compared to healthy controls (n = 24). Erythroid burst-forming units (BFU-Es) obtained by BM mononuclear or purified CD34+ cells were significantly lower in RA patients compared to controls. These abnormalities were more pronounced among patients with ACD. Increased TNF-[alpha] levels in patient long-term BM culture supernatants inversely correlated with BFU-Es and hemoglobin levels and positively with the percentage of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells. Following cA2 therapy, a normalization was documented in the number of CD34+/CD71+ and CD36[-]/glycoA+ cells, the number of BFU-Es, and the proportion of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells, which was associated with a significant increase in hemoglobin levels compared to baseline. Recovery from anemia was more prominent in patients with ACD. The exogenous addition of an anti-TNF-[alpha] antibody in the cultures increased BFU-E number in patients prior to cA2 treatment but not after treatment, further substantiating the inhibitory role of TNF-[alpha] on patients' erythropoiesis. We conclude that TNF-[alpha]-mediated apoptotic depletion of BM erythroid cells may account for ACD in RA and that cA2 administration may ameliorate ACD in these patients by down-regulating the apoptotic mechanisms involved in erythropoiesis. 10.1182/blood-2002-01-0136}, author = {Papadaki, Helen A. and Kritikos, Heraklis D. and Valatas, Vasilis and Boumpas, Dimitrios T. and Eliopoulos, George D.}, citeulike-article-id = {3401523}, citeulike-linkout-0 = {http://dx.doi.org/10.1182/blood-2002-01-0136}, citeulike-linkout-1 = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/100/2/474}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/12091338}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=12091338}, day = {28}, doi = {10.1182/blood-2002-01-0136}, journal = {Blood}, keywords = {anemia}, month = {June}, number = {2}, pages = {474--482}, posted-at = {2008-10-13 17:41:55}, priority = {2}, title = {Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone marrow erythroid cells: improvement following anti-tumor necrosis factor-alpha antibody therapy}, url = {http://dx.doi.org/10.1182/blood-2002-01-0136}, volume = {100}, year = {2002} }

TY - JOUR ID - citeulike:3401523 L3 - citeulike-article-id:3401523 N2 - Circumstantial evidence has implicated tumor necrosis factor [alpha] (TNF-[alpha]) in the pathogenesis of anemia of chronic disease (ACD) in rheumatoid arthritis (RA). We investigated the role of TNF-[alpha] in erythropoiesis of patients with active RA (n = 40) and the effect of anti-TNF-[alpha] antibody administration (cA2). Patients with RA had lower numbers of CD34+/CD71+ and CD36[-]/glycophorin A+ (glycoA+) bone marrow (BM) cells and increased proportions of apoptotic cells within the CD34+/CD71+ and CD36+/glycoA+ cell compartments, compared to healthy controls (n = 24). Erythroid burst-forming units (BFU-Es) obtained by BM mononuclear or purified CD34+ cells were significantly lower in RA patients compared to controls. These abnormalities were more pronounced among patients with ACD. Increased TNF-[alpha] levels in patient long-term BM culture supernatants inversely correlated with BFU-Es and hemoglobin levels and positively with the percentage of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells. Following cA2 therapy, a normalization was documented in the number of CD34+/CD71+ and CD36[-]/glycoA+ cells, the number of BFU-Es, and the proportion of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells, which was associated with a significant increase in hemoglobin levels compared to baseline. Recovery from anemia was more prominent in patients with ACD. The exogenous addition of an anti-TNF-[alpha] antibody in the cultures increased BFU-E number in patients prior to cA2 treatment but not after treatment, further substantiating the inhibitory role of TNF-[alpha] on patients' erythropoiesis. We conclude that TNF-[alpha]-mediated apoptotic depletion of BM erythroid cells may account for ACD in RA and that cA2 administration may ameliorate ACD in these patients by down-regulating the apoptotic mechanisms involved in erythropoiesis. 10.1182/blood-2002-01-0136 IS - 2 JF - Blood EP - 482 TI - Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone marrow erythroid cells: improvement following anti-tumor necrosis factor-alpha antibody therapy VL - 100 SP - 474 KW - anemia AU - Papadaki, Helen AU - Kritikos, Heraklis AU - Valatas, Vasilis AU - Boumpas, Dimitrios AU - Eliopoulos, George PY - 2002/06/28/ UR - http://dx.doi.org/10.1182/blood-2002-01-0136 ER -