1. Anti-COX-2 autoantibody is a novel biomarker of immune aplastic anemia
- Author
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Tiina Kelkka, Mikko Tyster, Sofie Lundgren, Xingmin Feng, Cassandra Kerr, Kohei Hosokawa, Jani Huuhtanen, Mikko Keränen, Bhavisha Patel, Toru Kawakami, Yuka Maeda, Otso Nieminen, Tiina Kasanen, Pasi Aronen, Bhagwan Yadav, Hanna Rajala, Hideyuki Nakazawa, Taina Jaatinen, Eva Hellström-Lindberg, Seishi Ogawa, Fumihiro Ishida, Hiroyoshi Nishikawa, Shinji Nakao, Jaroslaw Maciejewski, Neal S. Young, Satu Mustjoki, Medicum, TRIMM - Translational Immunology Research Program, Department of Clinical Chemistry and Hematology, University of Helsinki, Hematologian yksikkö, HUS Comprehensive Cancer Center, Faculty Common Matters (Faculty of Medicine), Faculty of Medicine, HUS Helsinki and Uusimaa Hospital District, Clinicum, and Digital Precision Cancer Medicine (iCAN)
- Subjects
Adult ,Cancer Research ,IDENTIFICATION ,Pancytopenia ,3122 Cancers ,Anemia, Aplastic ,Hematology ,ASSOCIATION ,DIAGNOSIS ,Oncology ,Cyclooxygenase 2 ,PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA ,CARBONIC-ANHYDRASE ,ANTIBODIES ,Humans ,HEMATOPOIETIC STEM-CELLS ,IMMUNOSUPPRESSIVE THERAPY ,MEGAKARYOPOIESIS ,Biomarkers ,Autoantibodies ,HLA-DRB1 Chains ,MYELODYSPLASTIC SYNDROME - Abstract
In immune aplastic anemia (IAA), severe pancytopenia results from the immune-mediated destruction of hematopoietic stem cells. Several autoantibodies have been reported, but no clinically applicable autoantibody tests are available for IAA. We screened autoantibodies using a microarray containing >9000 proteins and validated the findings in a large international cohort of IAA patients (n = 405) and controls (n = 815). We identified a novel autoantibody that binds to the C-terminal end of cyclooxygenase 2 (COX-2, aCOX-2 Ab). In total, 37% of all adult IAA patients tested positive for aCOX-2 Ab, while only 1.7% of the controls were aCOX-2 Ab positive. Sporadic non-IAA aCOX-2 Ab positive cases were observed among patients with related bone marrow failure diseases, multiple sclerosis, and type I diabetes, whereas no aCOX-2 Ab seropositivity was detected in the healthy controls, in patients with non-autoinflammatory diseases or rheumatoid arthritis. In IAA, anti-COX-2 Ab positivity correlated with age and the HLA-DRB1*15:01 genotype. 83% of the >40 years old IAA patients with HLA-DRB1*15:01 were anti-COX-2 Ab positive, indicating an excellent sensitivity in this group. aCOX-2 Ab positive IAA patients also presented lower platelet counts. Our results suggest that aCOX-2 Ab defines a distinct subgroup of IAA and may serve as a valuable disease biomarker.
- Published
- 2022