title: Ribosomal and immune transcripts associate with relapse in acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura.
abstract: Approximately 40% of patients who survive acute episodes of thrombotic thrombocytopenic purpura (TTP) associated with severe acquired ADAMTS13 deficiency experience one or more relapses. Risk factors for relapse other than severe ADAMTS13 deficiency and ADAMTS13 autoantibodies are unknown. ADAMTS13 autoantibodies, TTP episodes following infection or type I interferon treatment and reported ensuing systemic lupus erythematosus in some patients suggest immune dysregulation. This cross-sectional study asked whether autoantibodies against RNA-binding proteins or peripheral blood gene expression profiles measured during remission are associated with history of prior relapse in acquired ADAMTS13-deficient TTP. Peripheral blood from 38 well-characterized patients with autoimmune ADAMTS13-deficient TTP in remission was examined for autoantibodies and global gene expression. A subset of TTP patients (9 patients, 24%) exhibited a peripheral blood gene signature composed of elevated ribosomal transcripts that associated with prior relapse. A non-overlapping subset of TTP patients (9 patients, 24%) displayed a peripheral blood type I interferon gene signature that associated with autoantibodies to RNA-binding proteins but not with history of relapse. Patients who had relapsed bimodally expressed higher HLA transcript levels independently of ribosomal transcripts. Presence of any one potential risk factor (ribosomal gene signature, elevated HLA-DRB1, elevated HLA-DRB5) associated with relapse (OR = 38.4; p = 0.0002) more closely than any factor alone or all factors together. Levels of immune transcripts typical of natural killer (NK) and T lymphocytes positively correlated with ribosomal gene expression and number of prior episodes but not with time since the most recent episode. Flow cytometry confirmed elevated expression of cell surface markers encoded by these transcripts on T and/or NK cell subsets of patients who had relapsed. These data associate elevated ribosomal and immune transcripts with relapse history in acquired, ADAMTS13-deficient TTP.
authors: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, United States of America.
authors: Contessa E
authors: CE
authors: Edgar
authors: Department of Biostatistics & Epidemiology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, United States of America.
authors: Deirdra R
authors: DR
authors: Terrell
authors: Department of Biostatistics & Epidemiology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, United States of America.
authors: Sara K
authors: SK
authors: Vesely
authors: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, United States of America.
authors: Jonathan D
authors: JD
authors: Wren
authors: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, United States of America.
authors: Igor M
authors: IM
authors: Dozmorov
authors: Division of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Timothy B
authors: TB
authors: Niewold
authors: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, United States of America.
authors: Michael
authors: M
authors: Brown
authors: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, United States of America.
authors: Fang
authors: F
authors: Zhou
authors: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, United States of America.
authors: Mark Barton
authors: MB
authors: Frank
authors: Clinical Pharmacology Program, OMRF, Oklahoma City, Oklahoma, United States of America.
authors: Joan T
authors: JT
authors: Merrill
authors: Department of Hematology & Central Hematology Laboratory, Inselspital, Bern University Hospital & University of Bern, Bern, Switzerland.
authors: Johanna A
authors: JA
authors: Kremer Hovinga
authors: Department of Hematology & Central Hematology Laboratory, Inselspital, Bern University Hospital & University of Bern, Bern, Switzerland.
authors: Bernhard
authors: B
authors: Lämmle
authors: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, United States of America; Department of Medicine, OUHSC, Oklahoma City, Oklahoma, United States of America.
authors: Judith A
authors: JA
authors: James
authors: Department of Biostatistics & Epidemiology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, United States of America; Department of Medicine, OUHSC, Oklahoma City, Oklahoma, United States of America.
authors: James N
authors: JN
authors: George
authors: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, United States of America.
authors: A Darise
authors: AD
authors: Farris
mesh_terms: D051722:ADAM Proteins / Q000172:deficiency*; D000071120:ADAMTS13 Protein; D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011697:Purpura, Thrombotic Thrombocytopenic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D012270:Ribosomes / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007370:Interferon Type I; D012333:RNA, Messenger; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human