Work

Single-Nucleotide Polymorphisms in Thrombotic Thrombocytopenic Purpura: A Genetic Predisposition to Immune Thrombotic Thrombocytopenic Purpura

Year: 2024

Type: article

Abstract: There are two main classifications for thrombotic thrombocytopenic purpura (TTP): immune and hereditary. The majority of TTP cases are immune in nature and are due to inhibitor autoantibodies against ADAMTS13. Hereditary TTP is caused by biallelic pathogenic variants in the ADAMTS13 gene. Immune TTP is treated with therapeutic plasma exchange that both removes inhibitor autoantibodies and repletes deficient ADAMTS13. In hereditary TTP, the treatment is plasma infusion, as there are no inhibitor autoantibodies to remove. Our case report presents a 72-year-old male who experienced recurrent episodes of TTP and whose first episode was complicated by an occipital lobe stroke. Next-generation sequencing revealed three separate homozygous single-nucleotide polymorphisms (SNPs) in exon 1, exon 12, and exon 16 of the ADAMTS13 gene. Inhibitor autoantibody testing was negative in recurrent episodes, and treatment with plasma infusions for hereditary TTP led to relapses. The objective of our case report is to explore the combined effects of these SNPs on ADAMTS13 activity and antigen levels and question if these genetic variations can lower the threshold for an immune TTP episode. Future research is required to determine if lower-than-normal baseline ADAMTS13 activity levels can predispose a patient to TTP and the long-term complications associated with it.

Source: Cureus

DOI: 10.7759/cureus.75202

Authors: Alexander Konopnicki, Ariel Rischall, Bagi Jana

Institutions: The University of Texas Medical Branch at Galveston, Saint Louis University, The University of Texas MD Anderson Cancer Center

Language: English

Topic: Complement system in diseases

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

OpenAlex ID: W4405115756