Identification of proteinase 3 autoreactive CD4+T cells and their T-cell receptor repertoires in antineutrophil cytoplasmic antibody-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease involving autoreactivity to proteinase 3 (PR3) as demonstrated by presence of ANCAs. While autoantibodies are screened for diagnosis, autoreactive T cells and their features are less well-studied. Here, we investigated PR3-specific CD4+T cell responses and features of autoreactive T cells in patients with PR3-AAV, using a cohort of 72 patients with either active or inactive disease. Autoreactive PR3-specific CD4+T cells producing interferon γ in response to protein stimulation were found to express the G-protein coupled receptor 56 (GPR56), a cell surface marker that distinguishes T cells with cytotoxic capacity. GPR56+CD4+T cells were significantly more prominent in the blood of patients with inactive as compared to active disease, suggesting that these cells were affected by immunosuppression and/or that they migrated from the circulation to sites of organ involvement. Indeed, GPR56+CD4+T cells were identified in T-cell infiltrates of affected kidneys and an association with immunosuppressive therapy was found. Moreover, distinct TCR gene segment usage and shared (public) T cell clones were found for the PR3-reactive TCRs. Shared T cell clones were found in different patients with AAV carrying the disease-associated HLA-DP allele, demonstrating convergence of the autoreactive T cell repertoire. Thus, we identified a CD4+T cell signature in blood and in affected kidneys that display PR3 autoreactivity and associates with T cell cytotoxicity. Our data provide a basis for novel rationales for both immune monitoring and future therapeutic intervention in PR3-AAV.

Exploring the educational needs of patients with systemic vasculitis using the educational needs assessment tool.

Objectives: Knowledge and health literacy enable patients to monitor symptoms and disease impact. Educational needs have previously been explored in rheumatology, but scarcely for patients with ANCA-associated vasculitis (AAV). The aim of the study was to assess the educational needs among patients with AAV using the educational needs assessment tool (ENAT). Methods: This was a cross-sectional observational study including adults with AAV. Educational needs were captured by ENAT. Total ENAT (0-117 points, with higher numbers indicating higher educational need) and the seven domains (managing pain, movement, feelings, disease process, treatment, self-management and support systems) were explored regarding sex, age, education, diagnosis, disease duration and disease activity. To compare domains, a percentage response (0-100%) was calculated. Results: One hundred and seventy-eight individuals (50% men; 34% with disease duration ≤2 years) were included. The total ENAT mean was 66.5 (s.d. 26.6; 57%), with domains as follows: disease process, 78%; self-management, 69%; treatments, 64%; feelings, 56%; managing pain, 48%; support systems, 47%; and movement, 41%. Higher educational needs were found among women in the domains movement, feelings and disease process and in total ENAT (all P < 0.04) compared with men. Higher educational needs were also seen in patients with disease duration ≤2 years regarding disease process, self-management and support systems and in total ENAT compared with patients with longer disease duration (all P < 0.03). Conclusion: This study revealed great educational needs among AAV patients. Some groups expressed higher needs (women and those with shorter disease duration). Increased education for patients with AAV might lead to improved self-care and treatment adherence.

Venous thromboembolism in anti-neutrophil cytoplasmic antibody-associated vasculitis: an underlying prothrombotic condition?

OBJECTIVES: We investigated the incidence and potential underlying risk factors of venous thromboembolism (VTE) in patients with AAV. We assessed haemostatic disturbances and factors that might contribute to the risk of development of VTE. METHODS: ANCA-positive AAV patients (n = 187) were included. Previously identified risk factors for VTE and current medication were retrieved from the medical records. We assessed haemostasis using different methods [endogenous thrombin potential (ETP), overall haemostatic potential (OHP), overall coagulation potential (OCP) and overall fibrinolysis potential (OFP)] in patients with active AAV (n = 19), inactive AAV (n = 15) and healthy controls (n = 15). RESULTS: Twenty-eight VTEs occurred in 24 patients over a total follow-up time of 1020 person-years. A majority of VTEs occurred within the first year after diagnosis. Old age (P < 0.01), ongoing prednisolone treatment and recent rituximab administration were more common in the VTE group (P < 0.05 for all). ETP and OHP were significantly increased and OFP significantly decreased in plasma from active compared with inactive AAV patients (P < 0.05, P < 0.01 and P < 0.05, respectively) and healthy controls (P < 0.001). We could not confirm previously reported risk factors for VTE development. CONCLUSION: A high prevalence of VTE in AAV patients was seen within the first year after diagnosis, suggesting that disease activity contributes to development of VTE. Old age and concurrent treatment should also be taken into account when estimating VTE risk. The results also indicate disturbances in the haemostatic balance towards pro-thrombotic conditions in AAV patients, where ETP and OHP might be useful markers for identifying patients at high risk.

Proteinase 3 Autoreactivity in Anti-Neutrophil Cytoplasmic Antibody-associated vasculitis-Immunological versus clinical features.

ANCA-associated vasculitis (AAV) is a group of chronic inflammatory diseases of small- and medium-sized vessels, which are broadly subdivided based on organ manifestations and disease-specific autoantibodies. The so called anti-neutrophil cytoplasmic antibodies (ANCA) mostly target one of the enzymes, proteinase 3 (PR3) or myeloperoxidase (MPO). Accumulating genetic data demonstrates that these two autoantibodies discriminate two distinct disease entities, more so than the clinical subdivision which is mainly criteria-based. Treatment of AAV includes heavy immunosuppression and is guided by which organs that are involved. Generally, patients with PR3-ANCA display higher risk for disease relapse than patients with MPO-ANCA. In this review, we will focus on the autoimmune features of PR3+ AAV and our current understanding of its triggers and the potential translation into clinical practice.