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.

Immunological Analysis and Differential Genes Screening of Venous Thromboembolism

“…NR1D2 is also an important regulator of vascular in ammation and is related to the occurrence of cardiovascular events [35] . In a study of thrombotic thrombocytopenic purpura, immune gene transcription levels and ribosomal gene expression are associated with disease onset [36] , which is consistent with the conclusion of this paper.…”

Thrombotic Thrombocytopenic Purpura Following Pfizer-BioNTech COVID-19 Vaccination in a Patient With Multiple Myeloma: Case Report and Literature Review

“…There is robust evidence of the generation of autoantibodies by the vaccine antigens or the adjuvant components resulting in cross-reactivity with or without aberrant stimulation of the immune system leading to the development of autoimmune diseases [15]. Vaccine-induced formation of immune complexes containing RNA-binding proteins prompts an elevation in serum type-1 interferon immune activity, associated with the production of autoantibodies causing acquired deficiency of ADAMTS13 resulting in TTP [16,17]. COVID-19 mRNA vaccines have also been shown to induce an acquired deficiency of ADAMTS13 through the increased vWF release from the endothelium or the production of autoantibodies against ADAMTS13 via molecular mimicry between vaccine antigens and ADAMTS13.…”

Identify the influences of systemic lupus erythematosus on acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura using comprehensive bioinformatics analysis

“…The diagnosis of aTTP in all patients was confirmed by the detection of severe ADAMTS13 deficiency (activity <10%). 8…”

“…Gene chip and gene expression microarray are large-scale detections and efficient techniques, which are particularly proper for identifying different expression genes (DEGs) between diseases and normal tissues. Several studies using gene expression microarray and gene chip have been performed on SLE 7 or aTTP 8 to explore the DEGs. However, the underlying mechanisms in the pathogenesis of between SLE and aTTP remain mostly unclear.…”