The association between ambient UVB dose and ANCA-associated vasculitis relapse and onset
Authors: Scott Jennifer , Havyarimana Enock , Navarro-Gallinad Albert , White Arthur , Wyse Jason , van Geffen Jos , van Weele Michiel , Buettner Antonia , Wanigasekera Tamara , Walsh Cathal , Aslett Louis , Kelleher John D. , Power Julie , Ng James , O’Sullivan Declan , Hederman Lucy , Basu Neil , Little Mark A. , Zgaga Lina ,   on behalf of the RKD and UKIVAS groups, Little Mark , Lavin Peter , Wall Catherine , Mellotte George , Scott Jennifer , Fitzgerald Ted , O’Keefe Hannah , Dilworth Rachel , O’Neill Pamela , Carr Vicki , Conlon Niall , Griffin Brenda , Sexton Donal , Kosgei Caroline , O’Meara Yvonne , White Eoghan , Mahony Stephen , Molloy Eamonn , Holian John , Griffin Matt , Lappin David , Judge Conor , Cormican Sarah , O’Connell Blathnaid , Clince Michelle , Casserly Liam , Clarkson Michael , O’Shaughnessy Michelle , Verrelli Alyssa , Stoeman Sinead , Daly Fergus , Slattery Laura , Murphy Aisling , De Freitas Declan , Conlon Peter , Denton Mark , Treanor Carol , Magee Colm , Seaghdha Conall O. , O’Hara Paul , McGrath Susan , Moloney Brona , Moore Dean , Kelly Dearbhla , McCarthy Mary , Wanigasekera Tamara , Obilana Ayanfeoluwa , Kennedy Claire , Connaughton Dervla , Canney Mark , Wong Limy , Moran Sarah 
Published: June 2022

Background

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.

Methods

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. Ann-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.

Results

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.

Conclusion

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.