Distinguishing immunorelated haemocytopenia from idiopathic cytopenia of undetermined significance (ICUS): a bone marrow abnormality mediated by autoantibodies

Abstract

SummaryIn recent years we have observed that some patients with idiopathic cytopenia of undetermined significance (ICUS) responded well to corticosteroid and high-dose intravenous immunoglobulin treatment, indicating that some cytopenia in ICUS might be mediated by autoantibodies. In this study, we analysed 166 ICUS cases retrospectively, some of which were autoantibodies detected on haemopoietic cells in bone marrow (

Detection of erythroblast antibodies in mitogen‐stimulated bone marrow cultures from patients with myelodysplastic syndromes

“…In conclusion, we showed the presence of anti‐erythroblast autoimmunity in 66% of RA or RARS cases. Our findings are in line with those by Fu and coworkers who demonstrated the presence of a positive antiglobulin test on BM specimens from approximately 25% of patients with idiopathic cytopenia of undetermined significance, a condition that may precede MDS. The target cell of the autoimmune reaction belongs to a population of RBC precursors at different maturation stage, without the involvement of the EPO and EPO‐R pathway.…”

Lower level of IL‑35 and its reduced inhibition in Th17 cells in patients with bone marrow mononuclear cells Coombs test‑positive hemocytopenia

“…However, there is still a subset of patients who do not fulfill the criteria for MDS or other diseases even after a thorough follow-up time ( 12 ). Our previous study ( 5 ) tested IgM and IgG antibodies on various bone marrow cells membrane of various bone marrow cells of patients with ICUS by BMMNC-Coombs test, FCM and immunofluorescence analysis and determined that some patients had autoantibodies that lead to the immune dysfunction resulting in the destruction of BM hematopoietic cells and leading to hemocytopenia, which we termed as IRH. It is a type of hemocytopenia regarded as an autoimmune disease caused by unknown autoantibodies, which may suppress bone marrow hematopoietic cells, finally lead to the clinical manifestation of different degrees of anemia, bleeding and infection ( 4 , 5 ).…”

“…The positive rates of autoantibodies were tested by FCM on granulocytes (CD15 + ), stem cells (CD34 + ), nucleated erythrocytes (GlyCoA + ) using antibodies against CD15-FITC, CD34-FITC, GlycoA-FITC (5233893, 6082713 and 5288793; 1:10; BD Biosciences) and anti-human IgG-PE, IgM-APC antibodies (6144699 and 6042621; 1:10; BD Biosciences). As described in our previous study ( 5 ) a value of >4.0% was defined as positive. From these findings, all the enrolled patients with IRH were divided into three groups: i) Untreated patients; ii) remission patients with positive FCM results (remission + ); and iii) remission patients with negative FCM result (remission − ).…”

“…A total of 43 (25 females and 18 males; median age, 36 years; range, 11–69 years) patients with IRH were enrolled in the current study, including 18 untreated patients (11 females and 7 males; median age, 44.5 years; range, 16–68 years) and 25 in remission (14 females and 11 males; median age, 31 years; range, 11–69 years). All were inpatients in the Department of Hematology, Tianjin Medical University General Hospital (Tianjin, China) between August 2015 and September 2016 and diagnosed according to Fu ( 5 ). Patients were given corticosteroids (prednisone, 0.5 mg/kg/day) and cyclosporine (CsA) (3 mg/kg/day) as immunosuppressive therapy and some received high-dose IVIg (0.4 g/kg/day for 5 days; Chengdu Institute of Biological Products, Sichuan, China) if they depend on blood transfusion.…”

“…Bone marrow mononuclear cells (BMMNC)-Coombs test-positive hemocytopenia, also termed immunorelated hemocytopenia (IRH) is a type of hemocytopenia exhibiting these following features: i) Hemocytopenia or pancytopenia with a normal or higher percentage of reticulocytes and/or neutrophils; ii) hyperplasia-bone marrow (BM) with a higher percentage of nucleated erythroid cells in sternum, with erythroblastic islands (EIs) that were easily observed; iii) good responses to corticosteroids or high-dose intravenous immunoglobulin (IVIg); iv) exclusion of other primary and secondary hemocytopenia disorders; and v) positive result by BMMNC-Coombs test ( 4 , 5 ). This disease is an immuno-associated hemocytopenia and the production of the autoantibodies may be due to the abnormal number and function of B lymphocytes ( 6 ), regulatory T cells ( 7 ) and Th17 ( 8 ).…”