Detecting antibody target to improve diagnosis and prediction of treatment responses in patients with immune thrombocytopenia

Chief Investigator	Institution	Dates	Funding Stream	Amount
Dr Charlotte Bradbury	University of Bristol	Mar-2016 to Apr-2018	Above and Beyond Autumn 2015	£19,948

Summary

Immune thrombocytopenia (ITP) is an autoimmune illness that presents with bleeding due to reduced numbers of circulating blood platelets (cells essential for blood clotting). Bleeding can be life threatening and does not respond to platelet transfusions.

There is no diagnostic test for ITP and it can be difficult to distinguish from the many other causes of low platelets. It is also very difficult to predict which patients will have a mild brief ITP illness from those who have a severe, longer term form. In addition, patients respond differently to treatments and many patients are prescribed more than one type of medicine before finding one that works for them. This is highly unsatisfactory as they accumulate side effects from ineffective treatments and continue to be at high risk of bleeding, requiring intensive monitoring until their illness is controlled.

Antibodies are immune proteins that help fight infection but in ITP instead, they attack platelets and platelet producing cells. New research suggests that testing for these antibodies to identify exactly which protein on the surface of platelets they bind to (antibody specificity) can help with ITP diagnosis, predict illness severity and treatment responses.

This project aims to develop a laboratory blood test called the MAIPA to define antibody specificity in patients with ITP. This test is already used for other immune illnesses affecting platelets. If it can be refined for routine use in patients with ITP to help diagnosis and prediction of outcome, it could enable patients to get the right treatment sooner.

Work to date

We have recruited 68 patients with ITP to the Low platelet blood study (100% of those approached). The blood samples collected have been processed by laboratory staff who are not aware of the clinical outcome (response to treatment) to ensure results are blinded. Antibody specificity assays have been analysed in parallel with complementary work funded by Elizabeth Blackwell Institute.  Antibody specificity was analysed in 40 ITP patients using the Monoclonal antibody immobilisation of platelet antigen assay (MAIPA). Specific platelet autoantibodies were detected in 14 patients (35%) with ITP.  The other patients did not have detectable autoantibodies even following optimisation procedures of the assay. Antibody specificity did not predict response to treatment in this small patient cohort.  Platelet auto-antibodies were not found in any of the patients recruited with thrombocytopenia from another cause (thrombocytopenic controls, n=10). Therefore, a positive result using this assay may be helpful when there is diagnostic difficulty in patients with a low platelet count. However, a negative result does not exclude the diagnosis of ITP. 

Main findings

There is currently no diagnostic test for autoimmune thrombocytopenia (ITP) and diagnosis relies on the exclusion of other causes of thrombocytopenia which can be very difficult. We have demonstrated that in 35% of patients with ITP platelet specific auto-antibodies can be detected and these are not found in other causes of thrombocytopenia. Therefore, a positive result from this test may be helpful in patients in whom the diagnosis of ITP is difficult but a negative result does not exclude the diagnosis of ITP. For the patients with ITP in whom no platelet specific autoantibodies could be demonstrated even following optimisation of the assay, we hypothesise that alternative autoimmune mechanisms of platelet destruction may be involved (such as cell mediated cytotoxicity).

Larger grants

Funder, scheme, stage (outline/full), lead institution	Planned deadline or date submitted	Amount	Outcome / Status	Further details
NIHR RFPB	March 2016	£350,000	Awarded July 2016	PB-PG-0815-20016: FLIGHT Study
British Medical Association	Awarded September 2017	£50,000	Successful
ITP Support association	Awarded April 2017	£25,000	Successful

 

Other project outcomes

Ongoing collaboration with the ophthalmology research team ( Richard Lee, Andrew Dick), the ITP support association (national patient and public group) and the UK ITP forum (national clinical network of ITP clinicians)

Outputs

The antibody specificity work in ITP will be incorporated with complimentary research into a manuscript which is currently in preparation. We also plan to submit it as a conference abstract (BSH 2019).