Abstract: FR-PO135

Acquired Thrombotic Thrombocytopenic Purpura Secondary to Hereditary Autoimmunity: A Model for a New Pathogenic Mechanism?

Session Information

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • Marques, Sofia H., Centro Hospitalar de São João, Porto, Portugal
  • Carmo, Rute, Centro Hospitalar de São João, Porto, Portugal
  • Freitas, Ana Raquel oliveira, Centro Hospitalar de Entre o Douro e Vouga, Vale de Cambra, Portugal
  • Rodrigues, Pedro Silva, Centro Hospitalar de São João, Porto, Portugal
  • Martinho, Patricia, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal
  • Fidalgo, Teresa, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal
  • Pestana, Manuel, Centro Hospitalar de São João, Porto, Portugal
Background

Thrombotic thrombocytopenic purpura (TTP) may result from mutations of the ADAMTS13 gene (congenital TTP) or inactivating autoantibodies against the enzyme (acquired TTP).

Methods

We present the case of a 21-year-old male admitted for TTP with a suppressed ADAMTS13 enzyme activity (0%) and high titers of anti-ADAMTS13 antibody (99AU/mL) who was treated with plasmapheresis and rituximab. The patient’s mother had an episode of thrombotic microangiopathy in 1998 without major health issues since then. After her son’s disease, her blood tests were performed and revealed absent ADAMTS13 enzyme activity (0%) and positive anti-ADAMTS13 antibody (46AU/mL). Molecular studies were performed by a next generation sequencing - based gene panel (ADAMTS13, CFH, CFHR1, CFHR3, CFHR4, CFHR5, CFI, CFB, C3, THBD and DGKE), and no molecular abnormalities were detected. Results of HLA genotyping for both patients are displayed on Table 1.

Conclusion

As far as we know, this is the second report of an acquired TTP due to autoantibodies inactivating ADAMTS13 in two relatives. Our patients did not have any of the alleles which were associated by other authors with increased disease susceptibility. We discuss possible mechanisms behind hereditary antibody-mediated autoimmune diseases such as post-translational protein changes or epigenetic inherited processes. We also reflect on the fact that severe enzyme deficiency does not seem sufficient to express clinically as TTP and an environmental trigger may be required to precipitate an acute episode.

Table 1: HLA genotyping for patients 1 and 2
HLAPatient 1Patient 2
A*01:01/11:0111:01/30:02
B*37:01/55:0144:03/55:01
Cw*03:03/06:0203:03/04:01
DRB1*03/*10*03/*11
DQB1*02:01/*05:01*02:01/*03:01