Unraveling the Immunopathogenesis and Genetic Variants in Vasculitis Toward Development of Personalized Medicine

Abstract

Leukocytoclastic vasculitis (LCV) is a systemic autoimmune disease characterized by the inflammation of the vascular endothelium. Cutaneous small vessel vasculitis (CSVV) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are two examples of LCV. Advancements in genomic technologies have identified risk haplotypes, genetic variants, susceptibility loci and pathways that are associated with vasculitis immunopathogenesis. The discovery of these genetic factors and their corresponding cellular signaling aberrations have enabled the development and use of novel therapeutic strategies for vasculitis. Personalized medicine aims to provide targeted therapies to individuals who show poor response to conventional interventions. For example, monoclonal antibody therapies have shown remarkable efficacy in achieving disease remission. Here, we discuss pathways involved in disease pathogenesis and the underlying genetic associations in different populations worldwide. Understanding the immunopathogenic pathways in vasculitis and identifying associated genetic variations will facilitate the development of novel and targeted personalized therapies for patients.

SARS‐CoV‐2 vaccination‐induced cutaneous vasculitis: Report of two new cases and literature review

“…Leukocytoclastic vasculitis(LCV) represents a type of small vessel vasculitis, characterized by presence of neutrophil infiltrates, leukocytoclasis, fibrinoid necrosis, resulting in vessel walls damage 46 . Twenty cases of COVID‐19‐vaccine triggered‐LCV were noted; three with an elevated anti‐Spike SARS CoV‐2 Antibody titer, two of them had no history of COVID‐19.Oral mucosal involvement was noted in one case.…”

Cutaneous leukocytoclastic vasculitis associated with verapamil and atorvastatin: A case report

“…We postulate that the leukocytoclastic vasculitis resulted from a type III hypersensitivity reaction-where drug-induced aberrant antibody production leads to immune complex formation and deposition in small vessels causing vasculitis-thought to be the general mechanism in drug-induced leukocytoclastic vasculitis. 9 This is supported by positive IgM and complement staining on immunofluorescence, skin-limited disease, and rash onset within the typical window of 7-10 days after commencing medications. 1 However, the patient also had typical features of mixed cryoglobulinemic vasculitis-the purpuric rash with leukocytoclastic vasculitis, C4 hypocomplementemia, elevated RF and type II cryoglobulinemia with polyclonal and monoclonal IgM components-which would also account for positive IgM and C3 staining on immunofluorescence studies.…”

“…Future research into molecular mechanisms would be beneficial to better understand the properties of certain medications which mediate autoimmunity and clarify genetic susceptibility to drug-induced vasculitis. 9 In summary, we present a case of biopsy-proven leukocytoclastic vasculitis associated with verapamil and atorvastatin. We postulate the mechanism to be a type III hypersensitivity reaction or a drug-induced flare of cryoglobulinemic vasculitis secondary to Sjogren's syndrome.…”

“…We postulate that the leukocytoclastic vasculitis resulted from a type III hypersensitivity reaction—where drug‐induced aberrant antibody production leads to immune complex formation and deposition in small vessels causing vasculitis—thought to be the general mechanism in drug‐induced leukocytoclastic vasculitis 9 . This is supported by positive IgM and complement staining on immunofluorescence, skin‐limited disease, and rash onset within the typical window of 7–10 days after commencing medications 1 …”

Cutaneous vasculitis and vasculopathy in the era of COVID-19 pandemic

“…Skin-limited small vessel vasculitis or LCV ( 56 ) represents the most common CV reported after anti-SARS-CoV-2 vaccination. It has been observed after the Pfizer-BioNTech mRNA vaccine (BNT16B2b2) ( 57 – 65 ).…”