Vasculitis update: pathogenesis and biomarkers

Abstract

Better understanding of the pathogenesis and treatment of primary systemic vasculitides (PSV) has led to the development of many potentially clinically relevant biomarkers. Genome-wide association studies have highlighted that MHC class II polymorphisms may influence the development of particular anti-neutrophil cytoplasmic antibody (ANCA) serotypes, but not the clinical phenotype of ANCA-associated vasculitis (AAV). Although ANCAs are overall poor biomarkers of disease activity, they may be useful for the prediction of flares of renal and/or pulmonary vasculitis. Moreover, patients with proteinase 3 (PR3)-AAV may respond better to rituximab than cyclophosphamide. Newer biomarkers of renal vasculitis in AAV include urinary soluble CD163, and may in the future reduce the requirement for renal biopsy. Better understanding of dysregulated neutrophil activation in AAV has led to the identification of novel biomarkers including circulating microparticles, and neutrophil extracellular traps (NETs), although their clinical utility has not yet been realised. Studies examining endothelial injury and repair responses have additionally revealed indices that may have utility as disease activity and/or prognostic biomarkers. Last, next-generation sequencing technologies are revealing monogenic forms of vasculitis, such as deficiency of adenosine deaminase type 2 (DADA2), and are profoundly influencing the approach to the diagnosis and treatment of vasculitis in the young.

Primary angiitis of the central nervous system: diagnosis and treatment

“… 102 In addition, deficiency of adenosine deaminase type 2 (DADA2), an autosomal recessive disease, representing with lacunar stroke, vasculitic peripheral neuropathy, livedo racemosa and systemic inflammation is a possible differential diagnosis to PACNS with manifestation in early childhood. 103 …”

Clinical Perspective on Primary Angiitis of the Central Nervous System in Childhood (cPACNS)

“…Moreover, the measurement of VWF may be a valuable biomarker because a decrease in VWF levels in serum seems to indicate improvement of cPACNS disease activity (16). Von Willebrand factor antigen levels increase in serum in response to endothelial injury or activation; therefore, monitoring of VWF levels may reflect disease activity in many vasculitis (56,57). However, another study in pediatric PACNS found VWF levels to be a poor discriminator of disease activity, and a study of VWF in adults with antineutrophil cytoplasmic antibody-associated vasculitis observed the persistence of high levels of VWF when patients were considered to be in clinical remission (58,59).…”

Primäre entzündliche Ursachen zerebraler Ischämie im Kindesalter

“…Dies könnte sich jedoch durch internationale Kooperation und die Verwendung moderner Technologien in der nahen Zukunft ändern. Die Identifikation von Mutationen im für die Adenosin Deaminase 2 kodierende CECR1 Gen führte zur Beschreibung des Erkrankungsbildes DADA2 [10,31,32]. Ein Teil der Patienten mit vermuteter PACNS weist krankheitsauslösende Mutationen in CECR1 auf, was zur Reklassifikation dieser Fälle von PACNS zu DADA2 führt [10,31,32].…”

“…Die Identifikation von Mutationen im für die Adenosin Deaminase 2 kodierende CECR1 Gen führte zur Beschreibung des Erkrankungsbildes DADA2 [10,31,32]. Ein Teil der Patienten mit vermuteter PACNS weist krankheitsauslösende Mutationen in CECR1 auf, was zur Reklassifikation dieser Fälle von PACNS zu DADA2 führt [10,31,32]. Patienten mit DADA2 können erfolgreich mit TNF Blo- ckade therapiert werden [33].…”