Background/Aims: Antibodies against carbonic anhydrase (CA) have been detected in patients with an aplastic anemia (AA)-like syndrome after autologous stem cell transplantation. Methods: We analyzed sera of 53 bona fide AA patients before and after treatment with anti-thymocyte globulin (ATG) or bone marrow transplantation for the presence of anti-CA antibodies. Results: Anti-CA antibodies were detected in 20 patients (38%) and were associated with older age at diagnosis of AA. Antibody-positive patients showed poor response to ATG treatment (complete response 14%) and inferior long-term survival (36% at 10 years), when compared to antibody-negative patients (complete response and 10-year survival both 64%). Two thirds of patients with antibodies at diagnosis of AA became antibody negative after treatment with ATG. Clearance of the antibody did not appear to be associated with hematological improvement. Conclusion: Antibodies against CA are detected frequently at diagnosis of AA, and their presence identifies a subset of patients with poor response to immunosuppressive treatment.

Keywords:
Anti-thymocyte globulin, Aplastic anemia, Bone marrow transplantation, Carbonic anhydrase
1.
Young NS, Scheinberg P, Calado RT: Aplastic anemia. Curr Opin Hematol 2008;15:162–168.
2.
Scheinberg P, Nunez O, Weinstein B, Biancotto A, Wu CO, Young NS: Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med 2011;365:430–438.
3.
Nissen C, Stern M: Acquired immune mediated aplastic anemia: is it antineoplastic? Autoimmun Rev 2009;9:11–16.
4.
Bacigalupo A, Podesta M, Mingari MC, Moretta L, Van Lint MT, Marmont A: Immune suppression of hematopoiesis in aplastic anemia: activity of t-gamma lymphocytes. J Immunol 1980;125:1449–1453.
5.
Nakao S, Takami A, Takamatsu H, Zeng W, Sugimori N, Yamazaki H, Miura Y, Ueda M, Shiobara S, Yoshioka T, Kaneshige T, Yasukawa M, Matsuda T: Isolation of a T-cell clone showing HLA-DRB1*0405-restricted cytotoxicity for hematopoietic cells in a patient with aplastic anemia. Blood 1997;89:3691–3699.
6.
Hirano N, Butler MO, Von Bergwelt-Baildon MS, Maecker B, Schultze JL, O’Connor KC, Schur PH, Kojima S, Guinan EC, Nadler LM: Autoantibodies frequently detected in patients with aplastic anemia. Blood 2003;102:4567–4575.
7.
Lakota J, Skultety L, Dubrovcakova M, Altaner C: Presence of serum carbonic anhydrase autoantibodies in patients relapsed after autologous stem cell transplantation indicates an improved prognosis. Neoplasma 2008;55:488–492.
8.
Skultety L, Jankovicova B, Svobodova Z, Mader P, Rezacova P, Dubrovcakova M, Lakota J, Bilkova Z: Identification of carbonic anhydrase I immunodominant epitopes recognized by specific autoantibodies which indicate an improved prognosis in patients with malignancy after autologous stem cell transplantation. J Proteome Res 2010;9:5171–5179.
9.
Yoshida N, Yagasaki H, Takahashi Y, Yamamoto T, Liang J, Wang Y, Tanaka M, Hama A, Nishio N, Kobayashi R, Hotta N, Asami K, Kikuta A, Fukushima T, Hirano N, Kojima S: Clinical impact of HLA-DR15, a minor population of paroxysmal nocturnal haemoglobinuria-type cells, and an aplastic anaemia-associated autoantibody in children with acquired aplastic anaemia. Br J Haematol 2008;142:427–435.
10.
Speck B, Nissen C, Tichelli A, Gratwohl A: Treatment of aplastic anemia. Oncologist 1996;1:367–370.
11.
Camitta BM: What is the definition of cure for aplastic anemia? Acta Haematol 2000;103:16–18.
12.
Camitta BM, Thomas ED, Nathan DG, Gale RP, Kopecky KJ, Rappeport JM, Santos G, Gordon-Smith EC, Storb R: A prospective study of androgens and bone marrow transplantation for treatment of severe aplastic anemia. Blood 1979;53:504–514.
13.
Sugimori C, Yamazaki H, Feng X, Mochizuki K, Kondo Y, Takami A, Chuhjo T, Kimura A, Teramura M, Mizoguchi H, Omine M, Nakao S: Roles of DRB1 *1501 and DRB1 *1502 in the pathogenesis of aplastic anemia. Exp Hematol 2007;35:13–20.
14.
Inagaki Y, Jinno-Yoshida Y, Hamasaki Y, Ueki H: A novel autoantibody reactive with carbonic anhydrase in sera from patients with systemic lupus erythematosus and Sjogren’s syndrome. J Dermatol Sci 1991;2:147–154.
15.
Itoh Y, Reichlin M: Antibodies to carbonic anhydrase in systemic lupus erythematosus and other rheumatic diseases. Arthritis Rheum 1992;35:73–82.
16.
Liu H, Ozaki K, Matsuzaki Y, Abe M, Kosaka M, Saito S: Suppression of haematopoiesis by IGG autoantibodies from patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 1995;100:480–485.
17.
Feng X, Chuhjo T, Sugimori C, Kotani T, Lu X, Takami A, Takamatsu H, Yamazaki H, Nakao S: Diazepam-binding inhibitor-related protein 1: A candidate autoantigen in acquired aplastic anemia patients harboring a minor population of paroxysmal nocturnal hemoglobinuria-type cells. Blood 2004;104:2425–2431.
18.
Takamatsu H, Feng X, Chuhjo T, Lu X, Sugimori C, Okawa K, Yamamoto M, Iseki S, Nakao S: Specific antibodies to moesin, a membrane-cytoskeleton linker protein, are frequently detected in patients with acquired aplastic anemia. Blood 2007;109:2514–2520.
19.
Qi Z, Takamatsu H, Espinoza JL, Lu X, Sugimori N, Yamazaki H, Okawa K, Nakao S: Autoantibodies specific to HNRNP K: A new diagnostic marker for immune pathophysiology in aplastic anemia. Ann Hematol 2010;89:1255–1263.
20.
Takamatsu H, Yagasaki H, Takahashi Y, Hama A, Saikawa Y, Yachie A, Koizumi S, Kojima S, Nakao S: Aplastic anemia successfully treated with rituximab: the possible role of aplastic anemia-associated autoantibodies as a marker for response. Eur J Haematol 2011;86:541–545.
© 2012 S. Karger AG, Basel
2012
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