Autoimmune thrombocytopenia: flow cytometric determination of platelet-associated CD154/CD40L and CD40 on peripheral blood T and B lymphocytes.
OBJECTIVE
The CD40-CD40L system has pleiotropic effects in a variety of cells and biological processes including the immune response. Within the immune system, these molecules represent a critical link between its humoral and cellular arms. Immune or idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by antibody-induced platelet destruction and clearance due to anti-platelet autoantibodies, which bind to circulating platelets resulting in their destruction by the reticuloendothelial system. Despite its clinical importance, the diagnosis of ITP is one of exclusion, thus, inevitably associated with potential difficulties. CD40 is a cell surface receptor that belongs to the tumor necrosis factor-receptor (TNF-R) family, and that was first identified and functionally characterized on B lymphocytes. CD40-ligand (CD40L/CD154), a member of the TNF superfamily, is a cell membrane molecule expressed on activated CD4 + T lymphocytes and is essential for the T cell-dependent activation of B lymphocytes. Therefore it is now thought that CD40-CD40L interactions play a more important role in ITP immune regulation.


METHODS
The expressions of CD154 and CD40 on peripheral blood (PB) T and B lymphocytes, respectively, were measured using flow cytometry (FCM). An antigen-specific assay for platelet-associated CD154 (CD40L) on CD4 + T lymphocytes and for CD40 on CD19 + B lymphocytes was tested in 30 pediatric patients with acute ITP, 30 adult patients with chronic ITP, and in 20 age- and sex-matched healthy controls.


RESULTS
The expression of CD4 + CD154+ and CD4 + CD154+/CD4+ on PB T lymphocytes, and CD19 + CD40+ and CD19 + CD40+/CD19+ on PB B lymphocytes were significantly higher in acute and chronic ITP patients compared to controls, and in acute patients compared to chronics (p < 0.001).


CONCLUSIONS
CD40-CD40L interaction plays an important role in the pathology of certain autoimmune diseases. ITP is an autoimmune disease characterized by increased platelet destruction caused by anti-platelet autoantibodies, which mainly target a platelet surface antigen. It is speculated that platelet-associated CD154 is competent to induce the CD40-dependent proliferation of B lymphocytes. Therefore, platelet-associated CD154 expression is increased in ITP patients and is able to drive the activation of autoreactive B lymphocytes in this disease. These findings are particularly useful for clarifying the pathogenic process in ITP patients and for developing a therapeutic approach that blocks pathogenic anti-platelet antibody production. Blockade of the CD40/CD154 signal is a potential immunomodulatory strategy for T cell-mediated diseases, and many findings suggest that CD40/CD154 blockade therapy is potentially effective for ITP through selective suppression of autoreactive T and B lymphocytes to platelet antigens.
Meabed
Mohamed H
MH
Department of Pediatrics, Faculty of Medicine, Bani Suef University, Bani Suef, Egypt. mhmeabed@yahoo.com
Taha
Gamal M
GM
Mohamed
Seham O
SO
El-Hadidy
Khaled S
KS
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D018941:Antigens, CD19 / Q000032:analysis; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000737:chemistry*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry*; D019013:CD40 Antigens / Q000032:analysis*; D023201:CD40 Ligand / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008297:Male; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood* / Q000276:immunology / Q000473:pathology
D018941:Antigens, CD19; D001323:Autoantibodies; D019013:CD40 Antigens; D023201:CD40 Ligand