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The aberrant function of lymphocytes is considered a significant contributing factor to pure red cell aplasia (PRCA), but the precise mechanism by which T lymphocytes induce erythroid development stagnation remains unclear. In our study, the CD8 + T lymphocytes were isolated from bone marrow aspirates of acquired PRCA patients and healthy controls. RNA sequencing (RNA-Seq) was performed to analyze gene expression profiles. Additionally, the expression levels of key molecules and transcription factors were assessed at the transcription and protein levels. The RNA-Seq analysis revealed a significant upregulation of genes associated with the PI3K/AKT/mTOR pathway in CD8 + T lymphocytes from patients with PRCA, compared to healthy controls. The mRNA expression of AKT , mTOR and key transcription factors T-bet were significantly upregulated in CD8 + T cells from patients with PRCA. Treatment with rapamycin, an mTOR inhibitor, attenuated the activation of CD8 + T lymphocytes in PRCA patients. Our findings demonstrate the activation of the PI3K/AKT/mTOR signaling pathway in CD8 + T lymphocytes of PRCA patients, suggesting its involvement in PRCA pathogenesis. Targeting this pathway may offer a potential therapeutic strategy for PRCA characterized by CD8 + T cell dysregulation.

Purpose Acquired pure red cell aplasia (PRCA) is a kind of rare bone marrow failure disease characterized by destruction of erythrocyte by the immune system. However, the diverse etiologies of acquired PRCA make its pathogenesis largely unclear. Materials and methods We portrayed the clinicopathologic, mutation and TCR rearrangement profiles of 64 primary PRCA cases and 104 large granular lymphocytic leukemia (LGLL)-associated PRCA, and tried to reveal the association factors of CsA response. Results We found that gene mutations were detected in 39.7% of acquired PRCA who were older than 40 years, with DNMT3A , KMT2A and TP53 being the top 3 mutation genes. KMT2A mutation was only detected in patients with normal reticulocyte (Ret)%, while IDH1 mutation only occurred in patients with normal CD3 + CD8+/Lym%. For LGLL-associated PRCA patients, TRBV6_TRBJ2 was the most frequent dominant clonotype and the proportion of each dominant clone decreased following the remission of anemia. The response rate of LGLL-associated PRCA to CsA treatment was lower than primary PRCA (56.4% vs. 77.4%). β2-MG dysregulation, MF dysregulation were unfavorable factors for the response to CsA in PRCA patients, while other clinical information, mutated genes, number of mutated genes, mean VAF, number of TCR clones in PRCA patients did not significantly affect the response to CsA. Conclusion This study described the clinical features, mutation landscape and TCR rearrangement profile in a relatively larger PRCA cohort, which may contribute to the clear perception of PRCA and the development of more potent treatment approaches.

Background Thymoma‐associated pure red cell aplasia (PRCA) is a rare autoimmune disorder characterized by selective erythroid lineage suppression. However, the underlying immune mechanisms remain unclear. Methods We performed single‐cell RNA sequencing (scRNA‐seq) on bone marrow cells from thymoma‐PRCA patients and healthy controls to analyze hematopoietic cell populations. Additionally, we conducted bulk RNA sequencing of peripheral blood CD8 + T cells, flow cytometry analysis of CD8 + T‐cell activation, and cytokine profiling of bone marrow supernatant. Results scRNA‐seq revealed a significant reduction in erythroid progenitors (BFU‐E, CFU‐E, erythroblasts) and an increase in granulocyte‐monocyte progenitors (GMP) in thymoma‐PRCA patients. Differential gene expression analysis showed upregulation of TMSB10, AREG, and SPN, which are involved in immune modulation and T‐cell activation. Bulk RNA sequencing of CD8 + T cells indicated enhanced expression of activation markers (TNFRSF9, CTLA4, IRF4, CD38, MTHFD2) and decreased expression of erythroid‐related genes (HBA1, HBA2, HBB). Flow cytometry confirmed an increased CD8 + T‐cell population in the bone marrow, with elevated levels of perforin, granzyme B, IFN‐γ, and TNF‐α. Cytokine analysis further demonstrated increased IFN‐γ and TNF‐α levels in the bone marrow microenvironment. Conclusion Thymoma‐PRCA is associated with excessive CD8 + T‐cell activation and an inflammatory bone marrow environment, leading to impaired erythropoiesis. These findings provide novel insights into the immune dysregulation underlying thymoma‐associated PRCA and may help identify potential therapeutic targets. Single‐cell RNA sequencing reveals hematopoietic alterations in thymoma‐associated PRCA.

A 47‐year‐old woman was diagnosed with invasive thymoma 13 years ago. She had undergone repeated surgeries, as well as chemotherapy and radiation therapy. Chemotherapy was discontinued after the patient developed normocytic anemia, which was unresponsive to repeated blood transfusions. Bone marrow biopsy results revealed pure red cell aplasia (PRCA). Cyclosporine treatment led to improvement in PRCA; however, the patient died 3 years later from an invasive pneumococcal infection. The onset of thymoma‐associated PRCA remains unpredictable, and a significant delay may occur between the diagnosis of the two conditions. A 47‐year‐old woman was diagnosed with invasive thymoma 13 years ago. She had undergone repeated surgeries, as well as chemotherapy and radiation therapy. Chemotherapy was discontinued after the patient developed normocytic anemia. Bone marrow biopsy results revealed pure red cell aplasia (PRCA). Cyclosporine treatment led to improvement in PRCA.

Hemoproteins are critical for the function and integrity of aerobic cells. However, free heme is toxic. Therefore, cells must balance heme synthesis with its use. We previously demonstrated that the feline leukemia virus, subgroup C, receptor (FLVCR) exports cytoplasmic heme. Here, we show that FLVCR-null mice lack definitive erythropoiesis, have craniofacial and limb deformities resembling those of patients with Diamond-Blackfan anemia, and die in midgestation. Mice with FLVCR that is deleted neonatally develop a severe macrocytic anemia with proerythroblast maturation arrest, which suggests that erythroid precursors export excess heme to ensure survival. We further demonstrate that FLVCR mediates heme export from macrophages that ingest senescent red cells and regulates hepatic iron. Thus, the trafficking of heme, and not just elemental iron, facilitates erythropoiesis and systemic iron balance.

This current study retrospectively analyzed the clinical characteristics of 69 adult patients with acquired pure red cell aplasia (PRCA) including 40 elderly and 29 non-elderly patients from September 2009 to June 2019. The remission induction therapy regimens included cyclosporine A (CsA), corticosteroids (CS), or other immunosuppressive agents. The overall response rate was 55% (22/40) in the elderly group compared with 75.9% (22/29) in non-elderly patients (P = 0.075). In elderly patients, the best remission was achieved in the group treated with CsA than those treated with CS or other immunosuppressive agents (83.3% vs 26.7% vs 42.9%%, P = 0.004). However, outcomes of remission were similar among different treatment groups (P = 0.458) in non-elderly patients. CS induced a higher response rate in the non-elderly than that in the elderly (88.9% vs 26.7%, P = 0.009). By univariate and multivariate analysis, the clinical efficacy of elderly patients with acquired PRCA was closely associated with an induction regimen of CsA (P = 0.009; P = 0.017). In conclusion, CsA might produce higher response rate than CS and other drugs in elderly patients with acquired PRCA.

Acquired pure red cell aplasia (aPRCA) is rare and challenging to treat. We investigated the efficacy and safety of sirolimus plus roxadustat in patients with aPRCA (Chinese Clinical Trial Register number, ChiCTR2200065107). We enrolled 82 patients with aPRCA in this prospective single-arm, open-label, multicenter trial between October 2022 and January 2024. Treatment response and safety files were evaluated. The median age was 63 years. Seven patients withdrew during the trial period. Sirolimus plus roxadustat produced an overall response (OR) in 65 patients (90.3%) 3 months after initiation, which included a complete response (CR) in 39 (54.2%) and a partial response in 26 (36.1%). The 3-month CR rate was significantly higher in the newly diagnosed group (65.9% vs. 38.7%; P  = 0.022). The 6-month OR rate in the entire cohort was 93.0% (CR, 77.5%; PR, 15.5%). The mean hemoglobin concentration increased from 5.5 ± 1.6 g/dL at baseline to 11.6 ± 2.5 g/dL after 6 months of treatment. The proportions of patients who achieved transfusion independence within 1, 2, and 3 months of treatment were 57.4%, 76.6%, and 89.5%, respectively. The Functional Assessment of Chronic Illness Therapy-Fatigue Scale score and SF-36 survey score significantly improved after treatment. Treatment-related adverse events occurred in 24 patients (29.2%), and four events (4.9%) were grade ≥3. Sirolimus plus roxadustat is a promising treatment for aPRCA and has an acceptable safety profile, which warrants further investigation in a randomized setting.

Linezolid (LZD) is the first oxazolidinone with excellent safety and efficacy profiles against refractory infections caused by gram-positive organisms. Hematological toxicities such as thrombocytopenia, anemia, and leukocytopenia are common in LZD therapy; however, LZD-induced pure red cell aplasia (PRCA) is rare. An 83-year-old man diagnosed with pleural empyema caused by Staphylococcus aureus received LZD after developing resistance to multiple antibiotics. Although his infection-related symptoms were improved by LZD, progressive anemia was noticed after LZD therapy was initiated. Eight weeks after LZD administration began, his hemoglobin level was 5.7 g/dL and reticulocyte proportion was 0.36%, while his white blood cell and platelet counts remained unchanged since admission. Bone marrow examination revealed markedly decreased erythropoiesis with cytoplasmic vacuolation of erythroblasts. Anemia resolved by 14 days after cessation of LZD. It is important to increase the awareness among clinicians about the potential for the hematological effects associated with LZD, particularly for older patients with pre-existing anemia and treatment courses longer than 14 days. To detect bone marrow suppression, including PRCA, we suggest monitoring the complete blood count and reticulocyte count periodically in patients receiving long-term LZD therapy.

Association of parvovirus B19 infection with idiopathic collapsing glomerulopathy. Collapsing glomerulopathy (CG), a disorder with severe glomerular and tubular involvement, occurs either as an idiopathic lesion or in some patients with human immunodeficiency virus (HIV) infection known as HIV-associated nephropathy (HIVAN). We previously reported a renal transplant recipient with de novo CG and red cell aplasia in association with persistent parvovirus B19 (PVB19) infection. This prompted us to look for an association between PVB19 infection and CG. DNA from archived biopsies of patients with CG was analyzed for PVB19 by polymerase chain reaction (PCR). Results were compared with HIVAN, idiopathic focal segmental glomerulosclerosis (FSGS), and controls. In situ hybridization (ISH) was done to localize PVB19 in renal biopsies. Peripheral blood specimens of patients with CG, HIV infection, healthy controls, and randomly selected hospitalized patients (sick controls) were also analyzed for PVB19. PVB19 DNA was detected in renal biopsies of 18 out of 23 (78.3%) patients with CG, 3 out of 19 (15.8%) with HIVAN, 6 out of 27 (22.2%) with FSGS, and 7 out of 27 (25.9%) controls (P < 0.01, CG vs. HIVAN, FSGS, and controls). PVB19 was detected in peripheral blood of 7 out of 8 (87.5%) CG patients, 3 out of 22 (13.6%) with HIV infection, 4 out of 133 (3%) healthy controls, and 2 out of 50 (4%) sick controls (P < 0.001, CG vs. HIV infected, healthy, and sick controls). PVB19 was identified in glomerular parietal and visceral epithelial and tubular cells by ISH. The significantly higher prevalence of PVB19 DNA in renal biopsies and peripheral blood of CG patients suggests a specific association between PVB19 infection and CG. In susceptible individuals, renal epithelial cell infection with PVB19 may induce CG.