Researchers have discovered new mechanisms whereby auto immune disease develops and progresses, potentially altering the way patients are treated.
A review published in EBioMedicine analysed blood samples from 92 patients with thrombotic thrombocytopenic purpura (TTP), an auto immune disease in which blood clots form in small blood vessels throughout the body limiting or blocking the flow of oxygen-rich blood to the body's organs. TTP is caused by a lack of activity in the ADAMTS13 enzyme, a type of protein in the blood.
Up until now it was thought the ADAMTS13 enzyme was inhibited by its specific antibodies, however results have shown this to only be true in approximately 50% of cases. In the other 50%, antibodies were clearing the ADAMTS13 enzyme too quickly – this depletion of the ADAMTS13 antigen (the substance that causes the immune system to produce antibodies against it) was a dominant mechanism in the cause of TTP.
After analyses of antibodies from 43 patients , 15 showed no inhibition of the ADAMTS13 enzyme. 32 in 43 of the patients had some enzyme inhibition but not enough to account for severe enzyme deficiency.
The samples were obtained from the UK TTP registry, a cohort of samples from TTP cases in the UK. The registry started in 2009 and is the largest cohort of the rare disease in the world.
To analyse the samples researchers used a method called ‘epitope mapping’ which can identify the binding sites, or ‘epitopes’, of antibodies on their target antigens. This identification and characterisation of the binding sites of antibodies can aid in the discovery and development of new treatments.
The results have provided new insights into the pathophysiology of TTP and researchers hope their understanding of the mechanisms of ‘enzyme clearance’ will lead to more individualised tailoring of treatments by monitoring the amount of ADAMTS 13 produced and its activity.
This research was led by Dr Mari Thomas, a BRC funded Consultant Haemotologist at UCLH, during her PhD.
Dr Thomas was a PhD student under Dr Marie Scully. Dr Scully, Consultant Haematologist at UCLH, said: “Dr Thomas used samples from the UK TTP registry provided unique, valuable, scientific information about immune TTP that can be used to help us guide treatment.”
To read Pathogenicity of anti-ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura in full click here.
