Immunophenotype of Erythroid Precursors in Patient with Pure Red Cell Aplasia (PRCA): Utility of Analysis of Erythroid Maturation

Abstract

Pure Red Cell Aplasia (PRCA) is an infrequent disease [1,2], which usually presents as hypogenerative normochromic anemia, and is characterized by a significant decrease (including absence) of erythroid precursors [3]. Its etiology can be congenital or acquired, and its correct diagnosis requires exclusion of alternative cases of refractory anemia, so the bone marrow histology plays a crucial role. Myelodisplastic Syndromes (MDS) should always be considered in its differential diagnosis. The use of laboratory tools, specifically Flow Cytometry (FCM) is gained importance in the study of malignant and benign hematology pathologies. In MDS, FCM is not yet considered a standard of care, however it provides valuable information [4,5] and there are numerous publications and scores for its usual clinical use (for example Ogata score and RED-score [6,7]). In relation to the rise of FCM in MDS, enormous progress has been made in the description of the erythroid precursors immunophenotype [8-10]. An example of normal erythroid maturation is presented in Figure 1, showing proerythroblasts with immunophenotype CD71+ CD105+ CD117+, basophilic erythroblasts CD71+ CD105+ CD117-, polychromatophilic and orthochromatophilic erythroblasts CD71+ CD105- CD117- distinguishing by size in Forward Scatter (FSC) versus CD36 respectively. Characteristic maturation curve in CD117 versus CD105 analysis evidenced a predominance towards more mature erythroblasts.

Analysis of Immunophenotypic Changes during Ex Vivo Human Erythropoiesis and Its Application in the Study of Normal and Defective Erythropoiesis

“…MDS and PRCA represent the diseases of inefficient erythropoiesis [37,38] and have been classically defined by the increased coefficient of variation (CV) of CD36 and CD71 expression on the erythroid precursor. Previous studies have highlighted the same context with little focus on stage-specific aberrancies [31,41]. Recently, Yan et al broadly identified defects in an MDS group of patients with focus on erythroid stages [14]; however, in this research we studied all stages, from HSPCs to terminal stages, of erythroid differentiation and show that at progenitor stages, HSCs, MPPs, and BFU-E were severely decreased, with elevated levels of LMPPs, GMPs, and CFU-E in the MDS group.…”

“…MDS and PRCA patients represent clonal disorders of ineffective hematopoiesis that finally give rise to altered erythropoiesis [37,38]. Currently, the methods for identifying stagespecific erythroid dyspoiesis remain limited [14,[39][40][41]. Therefore, we tested the applicability of our marker panels to monitor erythroid differentiation in normal human bone marrow (BM), as well as in patients affected with MDS (erythroid dysplasia) and PRCA.…”