Successful treatment of amegakaryocytic thrombocytopenia with anti-CD20 antibody (rituximab) in a patient with systemic lupus erythematosus

Abstract

Amegakaryocytic thrombocytopenia is an extremely rare disorder in systemic lupus erythematosus, and its mechanism and treatment are still largely unknown. We describe a 42-year-old woman with systemic lupus erythematosus who presented various clinical manifestations of life-threatening amegakaryocytic thrombocytopenia (10,000 platelets/mm³ with a marked decrease of megakaryocytes in the bone marrow), proteinuria, psychosis, refractory chylothorax, ascites, and type II diabetes caused by the anti-insulin receptor autoantibody. She was initially treated with prednisolone (25–50 mg/day) and cyclosporine A (200 mg/day) without any improvement in severe thrombocytopenia. However, her clinical symptoms, including platelet counts, dramatically improved, with a concurrent decrease in the anti-c-Mpl antibody, an autoantibody against the thrombopoietin receptor, after a subsequent treatment with rituximab (375 mg/m² intravenously, weekly, for two consecutive weeks). Our case suggested that amegakaryocytic thrombocytopenia in patients with systemic lupus erythematosus might be mediated by the anti-c-Mpl antibody and could be treated with rituximab through elimination of pathogenic B cells producing autoimmune antibodies.

Keywords

amegakaryocytic thrombocytopenia rituximab (anti-CD20 mAb)SLE

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References

1 Singh RR . SLE: translating lessons from model systems to human disease. Trends Immunol 2005; 26: 572 – 579 .

2 Croker JA Kimberly RP . SLE: challenges and candidates in human disease. Trends Immunol 2005; 26: 580 – 586 .

3 Edwards JC Cambridge G . B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol 2006; 6: 394 – 403 .

4 Kuwana M Kaburaki J Okazaki Y Miyazaki H Ikeda Y . Two types of autoantibody-mediated thrombocytopenia in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2006; 45: 851 – 854 .

5 Agarwal N Spahr JE Werner TL Newton DL Rodgers GM . Acquired amegakaryocytic thrombocytopenic purpura. Am J Hematol 2006; 81: 132 – 135 .

6 Tristano AG . Acquired amegakaryocytic thrombocytopenic purpura: review of a not very well-defined disorder. Eur J Intern Med 2005; 16: 477 – 481 .

7 Wendling F Maraskovsky E Debili N . cMpl ligand is a humoral regulator of megakaryocytopoiesis. Nature 1994; 369: 571 – 574 .

8 Kuwana M Okazaki Y Kajihara M . Autoantibody to c-Mpl (thrombopoietin receptor) in systemic lupus erythematosus: relationship to thrombocytopenia with megakaryocytic hypoplasia. Arthritis Rheum 2002; 46: 2148 – 2159 .

9 Looney RJ Anolik J Sanz I . New therapies for systemic lupus erythematosus: cellular targets. Rheum Dis Clin North Am 2006; 32: 201 – 15 , xi.

10.

10 Tanaka Y Yamamoto K Takeuchi T . A multicenter phase I/II trial of rituximab for refractory systemic lupus erythematosus. Mod Rheumatol 2007; 17: 191 – 197 .

11.

11 Vallerskog T Gunnarsson I Widhe M . Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE. Clin Immunol 2007; 122: 62 – 74 .

12.

12 Anolik JH Barnard J Cappione A . Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus. Arthritis Rheum 2004; 50: 3580 – 3590 .

13.

13 Sun LY Zhang HY Feng XB Hou YY Lu LW Fan LM . Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus 2007; 16: 121 – 128 .

14.

14 Stasi R Pagano A Stipa E Amadori S . Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood 2001; 98: 952 – 957 .