ABSTRACT
BACKGROUND: HIV persists in a latent state in quiescent CD4 T cells preventing eradication of HIV. CD52 is a surface molecule modulated by HIV. We aimed at examining factors related to CD52 expression on CD4 T cells in HIV-positive individuals and the impact of initiation of combination antiretroviral therapy (cART). METHODS: Peripheral blood mononuclear cells from 18 HIV-positive individuals and 10 uninfected age- and sex-matched controls were examined by flow cytometry for CD38 and CD52 expression on CD4 T cells. Stimulation assays were performed on 8 healthy blood donors to determine a cutoff for CD52 expression. RESULTS: All examined CD4 T cells expressed CD52. However, both CD4 T cells with higher (CD52) and with lower CD52 expression (CD52dim) were found in HIV-positive individuals compared to uninfected controls. Two % CD52dim cells defined groups of high and low CD52: the group of individuals with high CD52 had higher CD4 counts at baseline (447 vs. 54 cells/µL, P = 0.02) and higher increase in CD4 counts during follow-up compared with low CD52 (P = 0.02). After 12 months of cART, CD52 increased (median fluorescence intensity 4846 vs. 5621, P < 0.05), whereas CD38 decreased (median fluorescence intensity 1519 vs. 730, P < 0.0001). CONCLUSIONS: All HIV-positive individuals in this cohort had CD4 T cells that expressed CD52. Higher CD4 counts were found in those with high CD52. Furthermore, an increase in CD52 was found after 12 months of cART, indicating that anti-CD52 antibodies may be more efficient for depletion of CD4 T cells in HIV-positive individuals on cART.
Subject(s)
Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active , CD4-Positive T-Lymphocytes/chemistry , CD52 Antigen/analysis , HIV Infections/drug therapy , HIV Infections/immunology , ADP-ribosyl Cyclase 1/analysis , Adult , CD4 Lymphocyte Count , Cohort Studies , Female , Flow Cytometry , Humans , Leukocytes, Mononuclear/immunology , Male , Membrane Glycoproteins/analysisABSTRACT
BACKGROUND: Aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH), and myelodysplastic syndrome (MDS) are the common spectrums of acquired bone marrow failure syndromes (BMFs). Accurate and timely diagnosis is a significant clinical challenge because of the overlapping features. The pathogenesis is not fully understood, but several studies have suggested that defective monocyte functions play an important role. We aimed to find whether the different expressions of CD52, CD14 and HLA-DR on CD4+ monocytes would be helpful in the preliminary diagnosis of acquired BMFs. METHODS: This study included 45 patients (21 AA patients, 13 MDS patients, 11 PNH patients). The control group was composed of 33 healthy adults. Flow cytometry was performed to determine the fluorochrome conjugated antibodies, including CD52, CD14 and HLA-DR. RESULTS: In this study, we found the expression of CD52 on CD4+ monocytes in AA patients was significant lower than MDS [15.90% (2.39 - 25.70) vs. 60.63% (26.0 - 94.98), p < 0.001] and healthy controls [15.90% (2.39 - 25.70) vs. 67.19% (25.5 - 88.4)%, p < 0.001], and a little higher than PNH patients [15.90% (2.39 - 25.70) vs. 4.55% (3.1 - 6.0), p < 0.05]. While comparing the levels of HLA-DR on CD4+ monocytes, AA patients were lower than PNH [40.05% (17.2 - 73.3) vs. 83.14% (80.7 - 94.3), p < 0.001] and MDS patients [40.05% (17.2 - 73.3) vs. 82.37% (69.1 - 91.2), p < 0.001]. CONCLUSIONS: According to our knowledge, this is a new clinical diagnostic method that uses surface markers for CD4+ monocytes such as CD52, CD14, and HLA-DR to make differential diagnoses within AA, PNH, and MDS patients in clinical practice. In addition, CD52 in patients shows that CD52 represents the most valuable molecular marker for differential diagnosis of three types of acquired BMFs.
