Increased frequency of bone marrow T follicular helper cells in patients with immune-related pancytopenia.

Hong Yu,Kai Ding,Hui Liu,Yihao Wang,Huaquan Wang,Jiangbo Zhang,Honglei Wang,Zonghong Shao,Rong Fu,Lijuan Li

doi:10.1155/2013/730450

Abstract

Immune-related pancytopenia (IRP) is one kind of bone marrow failure diseases which is related to autoantibodies. Autoantibodies have been detected on the membrane of various bone marrow (BM) hemopoietic cells by BM mononuclear-cell-Coombs test or flow cytometric analysis. There are autoantibodies in the BM supernatant of IRP patients, which can target several antigens on hematopoietic cells membranes by western blot. T follicular helper (Tfh) cells are the true helper cells for Ab responses, which represent one of the most numerous and important subsets of effector T cells. Dysregulation of Tfh cell function or expression of Tfh cell-associated molecules could contribute to the pathogenesis of autoimmune diseases. Currently, there are no studies regarding the role of Tfh cells in IRP patients. The percentages of Tfh cells, Tfh-related molecules ICOS, CD40L, IL-21, and Bcl-6 in BM were investigated in 90 patients with IRP, and 25 healthy controls. We observed that there exist increased quantity and hyperfunction of Tfh cells in IRP, and the results were correlated with patient characteristics. It was indicated that dysregulated Tfh cells might be involved in the pathogenesis of IRP and that inhibition of Tfh cells effector molecules might provide opportunities for new therapeutic approaches to IRP and even other human autoimmune diseases.

Highlights

We have described a group of patients with hemocytopenia who did not conform to the diagnostic criteria of known hematological and nonhematological diseases, such as aplastic anemia (AA), myelodysplastic syndrome (MDS), paroxysmal nocturnal hemoglobinuria (PNH), megaloblastic anemia (MA), iron deficiency anemia (IDA), anemia of chronic disease (ACD), autoimmune hemolytic anemia (AIHA), and congenital anemia
The proportion of patients showing positive results in the flow cytometry (FCM) was 83.3% (75/90), the BMMNC-Coombs test was 70% (63/90), and autoantibody IgG reacting with bone marrow (BM) cell membrane antigens could be found in BM supernatant of Immune-related pancytopenia (IRP) patients in a positive rate of 60% (54/90), respectively, which were significantly higher than normal controls (0%) (P < 0.01) (Figure 1, Table 1)
IRP is a disease differentiated from other bone marrow failure diseases, which have been described in recent years [2, 3, 15]

Summary

Introduction

We have described a group of patients with hemocytopenia who did not conform to the diagnostic criteria of known hematological and nonhematological diseases, such as aplastic anemia (AA), myelodysplastic syndrome (MDS), paroxysmal nocturnal hemoglobinuria (PNH), megaloblastic anemia (MA), iron deficiency anemia (IDA), anemia of chronic disease (ACD), autoimmune hemolytic anemia (AIHA), and congenital anemia. We detected autoantibodies on the membrane of BM hemopoietic cells by bone marrow mononuclear-cell-(BMMNC-) Coombs test [4,5,6] or flow cytometric analysis. The positive rate was 67% and 86%, respectively [7], indicating that this was an autoimmune disease. We termed this abnormality “immune-related Pancytopenia” (IRP) The production of autoantibodies in this disease was related to abnormal quantity and functions of B lymphocytes [11], caused by inhibition of regulatory T cells (Treg) [12], T helper (Th) 1, and activated Th2 [13] and Th17 [14] cells. Differentiating IRP from other diseases was beneficial for the treatment of IRP and other bone marrow failure diseases, such as AA, MDS, and PNH [15, 16]

Methods

Results

Conclusion