Background/Purpose: ANCA specificity has shown an association with patients’ genetic profile, cytokine profile, certain clinical presentations, serologic response to treatment, and risk of recurrence.Severe infections occur in approximately 35% of patients with ANCA-associated vasculitis, with a 4.4-fold increased risk compared to the general population. This risk is highest during the first year of the disease, during which infections represent the leading cause of death The aim of this study is to investigate the relationship between ANCA specificity and the risk of severe infection occurrence during the course of AAV.

Methods: This retrospective, observational study included patients diagnosed with AAV meeting the Chapel Hill Consensus Conference classification criteria who were treated at two hospital centers in southern France between January 1st 2010 and March 30th 2024.•The population was divided in two groups based on the presence or absence of anti-PR3 and anti-MPO ANCA. Patients without ANCA or with non-specific ANCA were excluded. The occurrence of severe infections—defined as those requiring hospitalization, surgical intervention, intravenous antibiotic therapy, or resulting in death—was assessed within three years following inclusion in patients enrolled during either a first onset or a relapse of vasculitis. We compared severe infection occurrence between the groups and conducted a proportional hazards Cox regression model adjusted for sex, age >65 years, FFS ≥1, respiratory involvement, relapse versus first onset status, and for induction therapy (with or without cyclophosphamide).

Results: Of the 529 screened patients, 270 were included in the analysis: 117 with PR3-ANCA vasculitis and 153 with MPO-ANCA vasculitis, of which 142 were GPA, 95 MPA, and 23 EGPA cases. The median age was 65.5 years [IQR: 57-75], and 48% were female. During follow-up, 89 patients (32.9%) developed a severe infection—57 (64.1%) in the MPO group and 32 (35.9%) in the PR3 group—corresponding to cumulative incidences of 7.34 and 4.12 cases per 100 person-years, respectively. Most infections occurred within the first year of follow-up, coinciding with the period of highest immunosuppressive burden. The median time to onset of severe infection was 8 months [range 1–19]; it was shorter in the MPO-ANCA group (4 months [range 1–18]) compared to the PR3-ANCA group (11 months [range 1.5–24]) (p=0.048). Bacterial pneumonia was the most frequently observed infection.The adjusted proportional hazards Cox regression model found an trend between the presence of anti-MPO ANCA and the risk of severe infection with a HR of 1.55 (95% CI: 0.97 – 2.48; p=0.06).

Conclusion: Our findings showed that MPO-ANCA specificity is associated with an increased risk of severe infections in patients with ANCA-associated vasculitis. Consistent with prior observations, most infections occurred within the first year of follow-up, with no significant difference in infection risk between cyclophosphamide and rituximab treatment arms. These results underscore the prognostic relevance of ANCA specificity in AAV.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-anca-specificity-on-risk-of-severe-infection-occurrence-in-anca-associated-vasculitis/