Many laboratory findings have demonstrated that the haemopoietic stem cell compartment is defective in aplastic anaemia (AA). AA bone marrow (BM) and peripheral blood (PB) are profoundly deficient in colony-forming cells, and AA progenitors fail to proliferate in long-term assays even in the presence of an intact stroma. Our study was designed to characterize some quantitative and qualitative aspects of the progenitor cell defect in AA. Using flow cytometric analysis of BM from new AA patients and from those recovering after immunosuppressive therapy, we determined that the numbers of CD34+ and CD33+ cells were markedly decreased in AA. Although PB neutrophil counts did not correlate with BM CD34+ cell numbers in acute disease, there was an association between the overall severity of the disease and the degree of CD34+ cell reduction. A decrease in BM CD33+ cells was a common finding in MDS patients, but reduction in CD34+ cells was found only in some hypoplastic MDS cases. Sorting experiments demonstrated lower plating efficiency for purified CD34+ cells from AA BM in comparison to controls. Thus, diminished colony formation of total BM appeared to result from both quantitative and qualitative defects. Based on the association between increased cycling and c-kit receptor expression on CD34+ cells, we found that the mitotically active CD34+ cells bearing the c-kit antigen were reduced in AA. With clinical improvement, CD34+ and CD33+ cells increased in correlation with PB parameters, but they did not return to normal values. Sorted CD34+ cells from recovered patents showed improved plating efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

We determined nine immune function parameters at diagnosis in patients with myelodysplastic syndromes (MDS) and correlated the results with the FAB classification and prognosis by univariate and multivariate analyses. Patients with refractory anaemia (RA) and refractory anaemia with ring sideroblasts (RAS) tended to have a higher CD4/CD8 ratio and a lower amount of γ‐globulins and soluble interleukin‐2 receptors in serum in comparison to those suffering from the other three subgroups of MDS. FAB classification, neutrophil and CD8 + T‐cell number had the best discriminatory capacity for predicting survival less than 1 year, and FAB classification, neutrophil number and serum TNF levels were predictors for conversion to acute leukaemia. The frequent occurrence of infections, on the other hand, could be better predicted by the absolute numbers of neutrophils and CD4 + cells and by the skin test score.

No abstract

Anemia is a frequent manifestation of rheumatoid arthritis, with a probably multifactorial etiology. We investigated the effect of peripheral blood mononuclear cell supernatants (PBMCS) from rheumatoid arthritis (RA) patients on hematopoietic colony formation in vitro, by using a methylcellulose assay. PBMCS from patients suppress in vitro erythroid (BFU‐E), mixed‐lineage (CFU‐GEMM) and to a lesser degree granulocyte‐macrophage (CFU‐GM) progenitors. PBMCS from anemic RA patients were more suppressive for BFU‐E than those from non‐anemic patients. Addition of antibodies to tumor‐necrosis factor alpha (TNFα) almost completely reversed the inhibition of BFU‐E and CFU‐GEMM, but had little effect on the CFU‐GM colony formation. Antibodies to interferon‐gamma (IFNγ) and interleukin‐1 (IL‐1) were not effective. The above data suggest that PBMCS from RA patients suppress in vitro erythropoiesis via the production of TNFα; a pathogenetic role for TNFα in the anemia of RA can be implied.