TNF-Alpha Antibody Improves Rheumatoid Arthritis-Associated Anemia

[Guest guest]

TNF-Alpha Antibody Improves Rheumatoid Arthritis-Associated Anemia

NEW YORK (Reuters Health) Jul 23 - An antibody to tumor necrosis factor

(TNF)-alpha, cA2, slows the apoptosis of bone marrow erythroid cells

associated with the anemia of chronic disease that often accompanies

rheumatoid arthritis, according to a report in the July 15th edition of

Blood.

While cA2 has been shown to increase hemoglobin levels in rheumatoid

arthritis patients with anemia of chronic disease (ACD), the authors

explain, the mechanism behind TNF-alpha's apparent modulation of

erythropoiesis is unclear.

Dr. Helen Papadaki, and colleagues from University of Crete School of

Medicine in Heraklion in Greece, investigated the role of TNF-alpha in

erythropoiesis of 40 patients with active rheumatoid arthritis. The effect

of cA2 administration on erythropoiesis was also evaluated.

Patients had significantly lower numbers of early erythroid precursor cells

than did healthy controls, the authors report, due principally to a relative

reduction in mature precursor cells (but not early precursor cells).

Similarly, the report indicates, the rheumatoid arthritis patients showed

increased apoptosis in the bone marrow erythroid progenitor and early

precursor cell compartments, but not in the mature precursor cell

population. The increased number of apoptotic cells probably reduced the

clonogenic potential of patient progenitor cells, investigators suggest.

TNF-alpha concentrations were significantly higher in the bone marrow

culture supernatants from patients with ACD than from nonanemic patients or

controls, the researchers note. This suggests that the " increased local

TNF-alpha production by bone marrow stromal cells probably accounts for the

apoptotic depletion of patient erythroid progenitor and early precursor

cells and is possibly involved in the pathogenesis of ACD in rheumatoid

arthritis. "

Administration of cA2 significantly increased the numbers of erythroid

progenitor and early precursor cells and decreased the numbers of apoptotic

cells in bone marrow culture.

Anti-TNF-alpha treatment, as expected, brought significant increases in

hemoglobin levels, mainly in the group of ACD patients, the investigators

report. Treatment also reduced peripheral cytokine levels (including IL-6

and IL-1-beta).

" We have provided...evidence that TNF-alpha-induced accelerated apoptosis of

bone marrow erythroid cells largely contributes to the pathogenesis of ACD

in rheumatoid arthritis patients, " the authors write. " TNF-alpha blockade

using cA2 improves ACD in rheumatoid arthritis patients and the beneficial

effect of the treatment is mediated, at least in part, by downregulating the

TNF-alpha-induced apoptotic mechanisms in the bone marrow. "

" Although future studies should help clarify our understanding of ACD, " Dr.

Mark J. Koury from Vanderbilt University School of Medicine in Nashville,

Tennessee, comments in a related editorial, " the results...point to a

prominent role of TNF-alpha in the apoptosis of erythroid cells. "

Blood 2002;100:373-374,474-482.

[Guest guest]

TNF-Alpha Antibody Improves Rheumatoid Arthritis-Associated Anemia

NEW YORK (Reuters Health) Jul 23 - An antibody to tumor necrosis factor

(TNF)-alpha, cA2, slows the apoptosis of bone marrow erythroid cells

associated with the anemia of chronic disease that often accompanies

rheumatoid arthritis, according to a report in the July 15th edition of

Blood.

While cA2 has been shown to increase hemoglobin levels in rheumatoid

arthritis patients with anemia of chronic disease (ACD), the authors

explain, the mechanism behind TNF-alpha's apparent modulation of

erythropoiesis is unclear.

Dr. Helen Papadaki, and colleagues from University of Crete School of

Medicine in Heraklion in Greece, investigated the role of TNF-alpha in

erythropoiesis of 40 patients with active rheumatoid arthritis. The effect

of cA2 administration on erythropoiesis was also evaluated.

Patients had significantly lower numbers of early erythroid precursor cells

than did healthy controls, the authors report, due principally to a relative

reduction in mature precursor cells (but not early precursor cells).

Similarly, the report indicates, the rheumatoid arthritis patients showed

increased apoptosis in the bone marrow erythroid progenitor and early

precursor cell compartments, but not in the mature precursor cell

population. The increased number of apoptotic cells probably reduced the

clonogenic potential of patient progenitor cells, investigators suggest.

TNF-alpha concentrations were significantly higher in the bone marrow

culture supernatants from patients with ACD than from nonanemic patients or

controls, the researchers note. This suggests that the " increased local

TNF-alpha production by bone marrow stromal cells probably accounts for the

apoptotic depletion of patient erythroid progenitor and early precursor

cells and is possibly involved in the pathogenesis of ACD in rheumatoid

arthritis. "

Administration of cA2 significantly increased the numbers of erythroid

progenitor and early precursor cells and decreased the numbers of apoptotic

cells in bone marrow culture.

Anti-TNF-alpha treatment, as expected, brought significant increases in

hemoglobin levels, mainly in the group of ACD patients, the investigators

report. Treatment also reduced peripheral cytokine levels (including IL-6

and IL-1-beta).

" We have provided...evidence that TNF-alpha-induced accelerated apoptosis of

bone marrow erythroid cells largely contributes to the pathogenesis of ACD

in rheumatoid arthritis patients, " the authors write. " TNF-alpha blockade

using cA2 improves ACD in rheumatoid arthritis patients and the beneficial

effect of the treatment is mediated, at least in part, by downregulating the

TNF-alpha-induced apoptotic mechanisms in the bone marrow. "

" Although future studies should help clarify our understanding of ACD, " Dr.

Mark J. Koury from Vanderbilt University School of Medicine in Nashville,

Tennessee, comments in a related editorial, " the results...point to a

prominent role of TNF-alpha in the apoptosis of erythroid cells. "

Blood 2002;100:373-374,474-482.