Vasculitis Pathogenesis: Can We Talk About Precision Medicine?

Abstract

Precision medicine is designing the medical care by taking into account the individual variability for each person. We have tried to address whether the existing data may guide precision medicine in primary systemic vasculitides (PSV). We have reviewed genome-wide association studies (GWAS) data, lessons from monogenic mimics of these diseases, and biomarker studies in immunoglobulin A vasculitis/Henoch–Schönlein purpura, Kawasaki disease, anti-neutrophil cytoplasmic antibody-associated vasculitis, polyarteritis nodosa (PAN), Takayasu arteritis, and Behçet’s disease (BD). GWAS provide insights about the pathogenesis of PSV while whole exome sequencing studies lead to discovery of monogenic vasculitides, phenotype of which could mimic other types of vasculitis such as PAN and BD. Monogenic vasculitides form a subgroup of vasculitis which are caused by single gene alterations and discovery of these diseases has enabled more specific therapies in these patients. With increasing number of studies on biomarkers, new targets for treatment appear and better and structured follow-up of PSV patients will become possible. Proteomics and metabolomics studies are required to better categorize our patients with PSV so that we can manage them appropriately and offer more targeted therapy.

Response to: ‘Tofacitinib for the treatment of polyarteritis nodosa: a literature review’. Correspondence on ‘Tofacitinib for polyarteritis nodosa: a tailored therapy’ by Rimaret al

“…Whole-exome sequencing studies may reveal novel mimickers, the monogenic vasculitides, as deficiency of adenosine deaminase 2, stimulator of interferon genes-associated vasculopathy with onset in infancy, and haploinsufficiency of A20 that should be considered in refractory cases. Finally, precision medicine, as we suggested in our report, may guide us in the future, helping us to find the right fit for each patient 6 7…”

New Insights and Challenges Associated With IgA Vasculitis and IgA Vasculitis With Nephritis—Is It Time to Change the Paradigm of the Most Common Systemic Vasculitis in Childhood?

“…Examples of such therapeutic options include budesonide, which can target Peyer's patches in the ileum where the production of Gd-IgA1 is thought to originate ( 77 ); bortezomib, a proteasome inhibitor which is a plasma cell depleting agent (it affects production of IgG autoantibodies) ( 78 ); complement inhibitors such as APL-2, CCX168, LNP023, and OMS721 ( 79 ); or the spleen tyrosine kinase inhibitors ( 80 ). Currently, precision medicine has not found its place in the treatment of vasculitis ( 81 ).…”

Does Autoimmunity Play a Role in the Immunopathogenesis of Vasculitis Associated With Chronic Chagas Disease?

“…The latter can be subdivided into ANCA-associated vasculitis (AAV) and immune complex small vessel vasculitis ( Shavit et al., 2018 ). Their pathogenesis is complex and diverse, and genetic and immunological determinants have been identified ( Ozen and Batu, 2018 ). However, a key feature of AAV which is not present in other vasculitides is the presence of ANCA directed against myeloperoxidase (MPO) or proteinase-3 (PR3), which are determinants for their pathogenesis ( Leacy et al., 2020 ).…”