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Anti-spacer idiotope profiles in iTTP patients
A
B
Figure 6. Disease outcome and treatment according to the anti-spacer idiotope profiles. Stratification of the 95 acute immune-mediated thrombotic thrombocy- topenic purpura (iTTP) patients of the French Reference Center for Thrombotic Microangiopathy according to the eight idiotope profiles for (A) the scoring system of Benhamou et al.39 (score < 3, white bars; score ≥ 3, black bars) and for (B) treatment with plasma exchange (PEX) with/without rituximab (white bars) or PEX with/without rituximab and additional treatment(s) (black bars). †Three patients died before treatment initiation and were excluded from the study (Online Supplementary Table S2).
relatively low number of patients per idiotope profile. Therefore, increasing the number of patients in each idiotope profile could show a link between certain profiles and disease severity. On the other hand, although the majority of iTTP patients do have autoantibodies against the cysteine-rich/spacer domain, autoantibodies targeting other regions within or outside the cysteine-rich/spacer domain could be important, as the immune response is polyclonal. Therefore, multiple anti-idiotypic antibodies recognizing a large number of anti-ADAMTS13 autoanti- bodies might be needed to identify autoantibody profiles in iTTP that predict disease outcome or that are linked with treatment. We are, therefore, currently expanding our panel of anti-idiotypic antibodies with anti-idiotypic antibodies recognizing anti-ADAMTS13 autoantibodies outside the spacer domain to identify autoantibody pro- files of clinical, prognostic value.
The strength of autoantibody profiling to predict dis- ease severity and outcome in an autoimmune disorder where autoantibodies are developed against a single self- antigen has been clearly demonstrated, for example, in myasthenia gravis. Indeed, it has been shown that the
presence of autoantibodies against a specific epitope in AChR is linked with disease severity in these patients.48,49 Therefore, the development of anti-idiotypic antibodies against anti-ADAMTS13 autoantibodies that are linked with disease severity, outcome, and relapse remains a promising approach to personalize treatment of iTTP patients.
In conclusion, we have shown that anti-idiotypic anti- bodies are useful to unravel anti-spacer autoantibody specificity in iTTP patients. Moreover, this approach is broadly applicable and can, therefore, be used to perform autoantibody profiling in any antibody-mediated autoim- mune disease.
Funding
This paper was supported by the following grant(s): the KU Leuven grants OT/14/071 and PF/10/014, and the European Framework Program for Research and Innovation (Horizon2020 Marie Sklodowska Curie Innovative training network PROFILE grant 675746). ASS is supported by a PhD grant from the Agency Innovation and Entrepreneurship (VLAIO, www.iwt.be), Flanders, Belgium (141136).
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