Proteinase 3 Autoreactivity in Anti‐Neutrophil Cytoplasmic Antibody–associated vasculitis—Immunological versus clinical features

Sharma, Ravi; Lövström, Björn; Gunnarsson, Iva; Malmström, Vivianne

doi:10.1111/sji.12958

Cited by 7 publications

(4 citation statements)

References 67 publications

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“…The pathogenesis of AAV is multifactorial and incompletely understood; however, a genetic component undoubtedly exists. There is compelling evidence that patients with MPO- and PR3-ANCA serotype exhibit different genetic association [ 27 ]. Published in 2012, the first genome-wide association study (GWAS) has provided robust evidence that GPA and MPA are different diseases and that the ANCA serotype more strongly correlates with genetic associations compared to the disease entities, further fueling the concept of a serology-based classification [ 28 ].…”

Section: Novel Findings In Genetics and Pathomechanismsmentioning

confidence: 99%

ANCA Status or Clinical Phenotype — What Counts More?

et al. 2021

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Purpose of Review There is ongoing debate concerning the classification of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. That is, whether classification should be based on the serotype (proteinase 3 (PR3)- or myeloperoxidase (MPO)-ANCA) or on the clinical phenotype (granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)). To add clarity, this review focused on integration of the most recent literature. Recent Findings Large clinical trials have provided evidence that a serology-based risk assessment for relapses is more predictive than distinction based on the phenotype. Research conducted in the past decade indicated that a serology-based approach more closely resembles the genetic associations, the clinical presentation (i.e., lung involvement), biomarker biology, treatment response, and is also predicting comorbidities (such as cardiovascular death). Summary Our review highlights that a serology-based approach could replace a phenotype-based approach to classify ANCA-associated vasculitides. In future, clinical trials and observational studies will presumably focus on this distinction and, as such, translate into a “personalized medicine.”

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Section: Novel Findings In Genetics and Pathomechanismsmentioning

confidence: 99%

ANCA Status or Clinical Phenotype — What Counts More?

et al. 2021

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“…Predicting which patients are more at risk of relapse is one of the major unmet needs in AAV clinical management, as it would help to modulate immunosuppression and minimise the risk of over/under-treatment. Besides their use as serological markers for AAV diagnosis, ANCA titres have shown to correlate with disease activity (5)(6)(7)(8)(9). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are also used as markers of active AAV in untreated patients at first presentation.…”

Section: Introductionmentioning

confidence: 99%

Autoantibodies towards HFE and SYT5 in anti-neutrophil cytoplasm antibody-associated vasculitis relapse

Bayati,

Nazeer,

et al. 2024

Preprint

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Objective: Identification of those at high and low risk of disease relapse is a major unmet need in the management of patients with ANCA-associated vasculitis (AAV). Precise stratification would allow tailoring of immunosuppressive medication. We profiled the autoantibody repertoire of AAV patients in remission to identify novel autoantibodies associated with relapse risk. Methods: Plasma samples collected from AAV patients in remission were screened for novel autoantibodies using in-house generated protein arrays including 42,000 protein fragments representing 18,000 unique human proteins. Patients were categorized based on the occurrence and frequency of relapses. We modelled the association between these antibodies and relapse occurrence using descriptive and high dimensional regression approaches. Results: We observed nine autoantibodies at higher frequency in samples from AAV patients experiencing multiple relapses compared to patients in long-term remission off therapy (LTROT). LASSO analysis identified six autoantibodies that exhibited an association with relapse occurrence after sample collection. Antibodies targeting HFE and SYT5 were identified as associated with relapse in both analyses. Conclusion: Through a broad protein array-based autoantibody screening, we identified two novel autoantibodies as candidate biomarkers of relapse in AAV.

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“…Meanwhile, neutrophils could also be activated and express PR3 and MPO to combine with the ANCA secreted by plasma cells (9)(10)(11). The fragment a of fifth complement (C5a) produced by activating cAP could connect with the C5a receptor on neutrophils (12,13).…”

Section: Introductionmentioning

confidence: 99%

“…On the genetic background, the interaction of infections, environmental and other factors might activate T cells, which could help B cells develop into plasma cells. Meanwhile, neutrophils could also be activated and express PR3 and MPO to combine with the ANCA secreted by plasma cells ( 9 – 11 ). The fragment a of fifth complement (C5a) produced by activating cAP could connect with the C5a receptor on neutrophils ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Targeting immune checkpoints in anti-neutrophil cytoplasmic antibodies associated vasculitis: the potential therapeutic targets in the future

et al. 2023

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Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a necrotizing vasculitis mainly involving small blood vessels. It is demonstrated that T cells are important in the pathogenesis of AAV, including regulatory T cells (Treg) and helper T cells (Th), especially Th2, Th17, and follicular Th cells (Tfh). In addition, the exhaustion of T cells predicted the favorable prognosis of AAV. The immune checkpoints (ICs) consist of a group of co-stimulatory and co-inhibitory molecules expressed on the surface of T cells, which maintains a balance between the activation and exhaustion of T cells. CD28, inducible T-cell co-stimulator (ICOS), OX40, CD40L, glucocorticoid induced tumor necrosis factor receptor (GITR), and CD137 are the common co-stimulatory molecules, while the programmed cell death 1 (PD-1), cytotoxic T lymphocyte-associated molecule 4 (CTLA-4), T cell immunoglobulin (Ig) and mucin domain-containing protein 3 (TIM-3), B and T lymphocyte attenuator (BTLA), V-domain Ig suppressor of T cell activation (VISTA), T‐cell Ig and ITIM domain (TIGIT), CD200, and lymphocyte activation gene 3 (LAG-3) belong to co-inhibitory molecules. If this balance was disrupted and the activation of T cells was increased, autoimmune diseases (AIDs) might be induced. Even in the treatment of malignant tumors, activation of T cells by immune checkpoint inhibitors (ICIs) may result in AIDs known as rheumatic immune-related adverse events (Rh-irAEs), suggesting the importance of ICs in AIDs. In this review, we summarized the features of AAV induced by immunotherapy using ICIs in patients with malignant tumors, and then reviewed the biological characteristics of different ICs. Our aim was to explore potential targets in ICs for future treatment of AAV.

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Proteinase 3 Autoreactivity in Anti‐Neutrophil Cytoplasmic Antibody–associated vasculitis—Immunological versus clinical features

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 7 publications

References 67 publications

ANCA Status or Clinical Phenotype — What Counts More?

ANCA Status or Clinical Phenotype — What Counts More?

Autoantibodies towards HFE and SYT5 in anti-neutrophil cytoplasm antibody-associated vasculitis relapse

Targeting immune checkpoints in anti-neutrophil cytoplasmic antibodies associated vasculitis: the potential therapeutic targets in the future

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