Expression levels of CD47, CD35, CD55, and CD59 on red blood cells and signal‐regulatory protein‐α,β on monocytes from patients with warm autoimmune hemolytic anemia

Abstract

BACKGROUND:Animal models have shown that CD47-deficient mice develop severe autoimmune hemolytic anemia (AIHA) because the binding of red blood cell (RBC) CD47 to signal-regulatory protein (SIRP-a) on macrophages contributes to the inhibition of phagocytosis. In contrast, complement-inhibitory proteins such as CD35, CD55, and CD59 may protect RBCs against the lysis by complement. STUDY DESIGN AND METHODS:With the use of flow cytometric analyses, the expression of CD47, CD35, CD55, and CD59 on RBCs and of SIRP-a,b on peripheral monocytes of 36 patients with warm AIHA (wAIHA; 23 with active wAIHA, 13 with wAIHA in remission) and 20 healthy subjects was evaluated. RESULTS: The mean fluorescence intensities (MFIs) of the expression of CD47, CD35, CD55, and SIRP-a,b of active wAIHA patients, wAIHA in remission, and healthy subjects were not statistically different. Patients with active wAIHA showed significantly lower CD59 expression on RBCs than healthy individuals (MFI, 512.5 Ϯ 59.6 vs. 553.7 Ϯ 36.6; p = 0.009), while the CD59 expression in patients with wAIHA in remission was not significantly different from that of healthy controls (MFI, 538.4 Ϯ 48.3 vs. 553.7 Ϯ 36.6; p > 0.05). The expression of CD59 on RBCs of 3 patients who died from the wAIHA was lower than that seen on RBCs of healthy controls (MFI, 433.6 Ϯ 69.6 vs. 553.74 Ϯ 36.6; p = 0.0001). CONCLUSIONS: Our data show that the expression of CD47 on RBCs and SIRP-a,b on monocytes of patients with wAIHA is not different from that seen in healthy individuals. In addition, we detected that patients with active wAIHA present low expression of CD59 and normal expression of CD35 and CD55 on their RBCs. Complement-regulatory proteins may play an important role in protecting RBC destruction through the activation of complement.

NF-κB and Enhancer-binding CREB Protein Scaffolded by CREB-binding Protein (CBP)/p300 Proteins Regulate CD59 Protein Expression to Protect Cells from Complement Attack

“…2B, inset). Meanwhile, it has been suggested that the deficient expression of mCRPs, especially CD59, is associated with autologous cell destruction by complement attack in autoimmune disorders, such as autoimmune hemolytic anemia, systemic lupus erythematosus, autoimmune thrombocytopenia, and aplastic anemia (4,5,30), possibly resulting from NF-B dysfunction due to genetic mutation (31). In addition, mouse CD59 genetic deficiency promotes atherogenesis in animal models (32); similarly, this study revealed the pathogenic roles of CD59 in atherosclerosis, a chronic inflammatory and immune vascular disease (33).…”

Experimental immunology Expression levels of CD47 on red blood cells during their storage in blood bank

“…Probably it is caused by phylogenetic divergence and species specificity at a biochemical and genetic level [9,13,16]. Also, one should not compare the RBC senescence in vivo and in vitro [16].…”

“…Some of important roles of CD47 are suspected for example to be regulation of the migration, proliferation, survival of blood cells and some processes of innate and adaptive immunity. As a receptor of protein thrombospondin-1, it influences NO role in regulation of blood pressure, vascular flow and haemostasis [9][10][11]. The aim of this study is to DOI: 10.5114/ceji.2013.35205 compare the CD47 expression on RBCs from "fresh" and "old" units with and without leucocytes.…”

Autoimmune hemolytic anemia: transfusion challenges and solutions

“…We have recently reported a RBC alloantibody prevalence of 11.1% in Brazilian patients with true AIHA. 30 The clinical physician attending patients with AIHA should understand that the aforementioned aspects of pretransfusion compatibility testing on AIHA patients are complex, and thus consider that a longer period of time is necessary for the blood bank to perform the complete panel of immunohematological tests which are necessary to guarantee the best RBC product for transfusion.…”

“…1,26 The prevalence of RBC alloantibodies in patients with WAIHA ranges from 7.5% to 54% (Table 3). 17,23,[27][28][29][30][31][32][33] The majority of studies reporting on the high frequency of coexisting alloantibodies and autoantibodies mostly describe patients with serological positive results rather than with clinically confirmed WAIHA. We have recently reported a RBC alloantibody prevalence of 11.1% in Brazilian patients with true AIHA.…”