The aetiology of ANCA-associated vasculitis (AAV) and triggers of relapse are poorly understood. Vitamin D (vitD) is an important immunomodulator, potentially responsible for the observed latitudinal differences between granulomatous and non-granulomatous AAV phenotypes. A narrow ultraviolet B spectrum induces vitD synthesis (vitD-UVB) via the skin. We hypothesised that prolonged periods of low ambient UVB (and by extension vitD deficiency) are associated with the granulomatous form of the disease and an increased risk of AAV relapse. Patients with AAV recruited to the Irish Rare Kidney Disease (RKD) (n = 439) and UKIVAS (n = 1961) registries were studied. Exposure variables comprised latitude and measures of ambient vitD-UVB, including cumulative weighted UVB dose (CW-D-UVB), a well-validated vitD proxy. An n-of-1 study design was used to examine the relapse risk using only the RKD dataset. Multi-level models and logistic regression were used to examine the effect of predictors on AAV relapse risk, phenotype and serotype. Residential latitude was positively correlated (OR 1.41, 95% CI 1.14–1.74, p = 0.002) and average vitD-UVB negatively correlated (0.82, 0.70–0.99, p = 0.04) with relapse risk, with a stronger effect when restricting to winter measurements (0.71, 0.57–0.89, p = 0.002). However, these associations were not restricted to granulomatous phenotypes. We observed no clear relationship between latitude, vitD-UVB or CW-D-UVB and AAV phenotype or serotype. Our findings suggest that low winter ambient UVB and prolonged vitD status contribute to AAV relapse risk across all phenotypes. However, the development of a granulomatous phenotype does not appear to be directly vitD-mediated. Further research is needed to determine whether sufficient vitD status would reduce relapse propensity in AAV.

中文翻译：

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环境 UVB 剂量与 ANCA 相关性血管炎复发和发作之间的关联

对 ANCA 相关性血管炎 (AAV) 的病因和复发的诱因知之甚少。维生素 D (vitD) 是一种重要的免疫调节剂，可能导致肉芽肿和非肉芽肿 AAV 表型之间观察到的纬度差异。窄的紫外线 B 光谱通过皮肤诱导 vitD 合成 (vitD-UVB)。我们假设长时间的低环境 UVB（以及延伸的 vitD 缺乏）与该疾病的肉芽肿形式和 AAV 复发的风险增加有关。对爱尔兰罕见肾脏病 (RKD) (n = 439) 和 UKIVAS (n = 1961) 登记处招募的 AAV 患者进行了研究。暴露变量包括纬度和环境 vitD-UVB 的测量值，包括累积加权 UVB 剂量 (CW-D-UVB)，这是一种经过充分验证的 vitD 代理。n-of-1 研究设计用于仅使用 RKD 数据集检查复发风险。多水平模型和逻辑回归用于检查预测因子对 AAV 复发风险、表型和血清型的影响。居住纬度与复发风险呈正相关（OR 1.41, 95% CI 1.14–1.74, p = 0.002），平均 vitD-UVB 与复发风险呈负相关（0.82, 0.70–0.99, p = 0.04），当限制在冬季时效果更强测量值 (0.71, 0.57–0.89, p = 0.002)。然而，这些关联并不局限于肉芽肿表型。我们观察到纬度、vitD-UVB 或 CW-D-UVB 与 AAV 表型或血清型之间没有明确的关系。我们的研究结果表明，冬季环境 UVB 低和 vitD 状态延长会导致所有表型的 AAV 复发风险。然而，肉芽肿表型的发展似乎不是直接由 vitD 介导的。需要进一步的研究来确定足够的 vitD 状态是否会降低 AAV 的复发倾向。