Additional file 1 of The association between ambient UVB dose and ANCA-associated vasculitis relapse and onset
Creators: name: Scott, Jennifer
name: Havyarimana, Enock
name: Navarro-Gallinad, Albert
name: White, Arthur
name: Wyse, Jason
name: van Geffen, Jos
name: van Weele, Michiel
name: Buettner, Antonia
name: Wanigasekera, Tamara
name: Walsh, Cathal
name: Aslett, Louis
name: Kelleher, John D.
name: Power, Julie
name: Ng, James
name: O’Sullivan, Declan
name: Hederman, Lucy
name: Basu, Neil
name: Little, Mark A.
name: Zgaga, Lina
Publisher: name: figshare
Year: 2022
Subjects: subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Genetics
subject: Molecular Biology
subject: Biotechnology
subject: Immunology
subject: FOS: Clinical medicine
subject: 19999 Mathematical Sciences not elsewhere classified
subject: FOS: Mathematics
subject: Cancer
subject: 110309 Infectious Diseases
subject: FOS: Health sciences

description: Additional file 1: Fig. S1. Flowchart of participant selection for the UKIVAS cohort (1). Fig. S2. Flowchart of participant selection for the RKD cohort (2). Fig. S3. Participant locations at diagnosis for i). UKIVAS and ii). RKD cohort. Shading represents the absolute number of participants recruited to the study in that region, at the time of their diagnosis. Tendency to cluster around vasculitis referral centres is observed. Fig. S4. Distribution of vitD-UVB (kJ/m2) (a and b) and CW-D-UVB (kJ/m2) (c and d) by month and season: CW-D-UVB peaks in late summer and nadirs in winter. Fig. S5. The relationship between latitude (degrees) and a). annual daily average vitD-UVB (kJ/m2, Pearson correlation coefficient (corr) -0.98, p &lt;0.001), b). annual daily average CW-D-UVB (kJ/m2, corr -0.96, p &lt;0.001). CW-D-UVB at diagnosis c). not adjusted for season (kJ/m2, corr -0.12, p &lt;0.001), and d-g). stratified by season (corr winter -0.25, spring -0.15, summer -0.47, autumn -0.22, p &lt;0.001 for all). Fig. S6. The relationship between latitude (degrees) and a). annual daily average vitD-UVB (kJ/m2, Pearson correlation coefficient (corr) -0.98, p &lt;0.001), b). annual daily average CW-D-UVB (kJ/m2, corr -0.96, p &lt;0.001). CW-D-UVB at diagnosis c). not adjusted for season (kJ/m2, corr -0.12, p &lt;0.001), and d-g). stratified by season (corr winter -0.25, spring -0.15, summer -0.47, autumn -0.22, p &lt;0.001 for all). Fig. S7. AAV diagnosis: a). Latitude (degrees), b). average annual vitD-UVB (kJ/m2), c). average winter vitD-UVB (kJ/m2) and d). CW-D-UVB (kJ/m2) stratified by AAV phenotype (GPA and EGPA (“Not MPA”) vs. MPA), at diagnosis. ANCA-associated vasculitis (AAV), Microscopic polyangiitis (MPA), Ambient UVB dose at wavelengths than induce vitD synthesis (vitD-UVB), Cumulative-weighted UVB dose (CW-D-UVB). Fig. S8. AAV diagnosis: Latitude (degrees), average annual vitD-UVB (kJ/m2), average winter vitD-UVB (kJ/m2) and CW-D-UVB (kJ/m2) stratified by AAV serotype (a-d: MPO vs. Not MPO), at diagnosis. ANCA-associated vasculitis (AAV), Myeloperoxidase (MPO), Cumulative-weighted UVB dose (CW-D-UVB). Fig. S9. Ratio of cumulative-weighted UVB at diagnosis relative to the average value at the participant’s location: a). cohort 1 &amp; 2 and stratified by b). AAV phenotype and c). AAV serotype. ANCA-associated vasculitis (AAV), Microscopic polyangiitis (MPA), Myeloperoxidase (MPO), Cumulative-weighted UVB dose (CW-D-UVB), Not statistically significant (ns). If a true association between UVB-predicted vitD status (CW-D-UVB) and AAV phenotype/serotype at diagnosis exists, one would expect that the ratio of CW-D-UVB at diagnosis relative to the average CW-D-UVB at that location would be significantly &lt;1 for non-MPA disease subtypes. A one-sided Wilcoxon rank sum test was used to evaluate if the ratio was significantly different from 1. While the median ratio trended below 1 in the pooled analysis and when stratified by AAV phenotype and serotype, this was not statistically different from 1. Table S1. Induction and maintenance treatment of RKD cohort (2). Intravenous (IV). Table S2. Multi-level model investigating the factors associated with AAV relapse risk, stratified by AAV phenotype (sensitivity analysis). N (individuals) differs from N (observations) as multiple observations (remission +/- relapse) per individual were included, according to each participant’s disease course. The OR refers to the probability of having an AAV relapse (relative to remission). Model 1 investigates the effect of average winter (Dec-Feb) vitD-UVB (2004-2019), adjusted for age at diagnosis, gender, AAV phenotype, ANCA serotype and treatment, restricted to MPA phenotype. Model 2 investigates the effect of average winter (Dec-Feb) vitD-UVB (2004-2019), adjusted for age at diagnosis, gender, AAV phenotype, ANCA serotype and treatment, restricted to Not MPA phenotype. Cumulative-weighted UVB dose (CW-D-UVB), Standard deviation (SD), Microscopic polyangiitis (MPA), Myeloperoxidase (MPO), Odds ratio (OR), 95% Confidence interval (95% CI). Table S3. Multi-level model investigating the association between CW-D-UVB and the risk of AAV relapse (with treatment breakdown). N (individuals) = 439, N (observations) = 2080 as multiple observations (remission +/- relapse) per individual were included according to each participant’s disease course. The OR refers to the probability of having an AAV relapse (relative to remission). Cumulative-weighted UVB dose (CW-D-UVB), Standard deviation (SD), Microscopic polyangiitis (MPA), Myeloperoxidase (MPO), Odds ratio (OR), 95% Confidence interval (95% CI), Azathioprine (AZA), Mycophenolate mofetil (MMF), Methotrexate (MTX). Table S4. Uni- and multivariable logistic regression analysis of factors associated with AAV serotype at diagnosis, in the combined UKIVAS and RKD cohort. Note: OR (95% CI, p). The OR refers to the probability of having MPO-positivity (ref: not MPO-ANCA) at diagnosis. Model 1 investigates the effect of latitude, adjusted for age at diagnosis, gender and ethnicity (observations 1260, 1053 missing ANCA serology, AIC 1626.9). Model 2 investigates the effect of average annual vitD-UVB, adjusted for age at diagnosis, gender and ethnicity (observations 1260, 1053 missing ANCA serology, AIC 1626.8). Model 3 investigates the effect of average winter (Dec-Feb) vitD-UVB (2004-2019), adjusted for age at diagnosis, gender and ethnicity (observations 1260, 1053 missing ANCA serology, AIC 1626.5). Model 4 investigates the effect of CW-D-UVB at symptom onset, adjusted for age at diagnosis, gender and ethnicity (observations 1260, 1053 missing ANCA serology, AIC 1627.3). Ambient UVB dose at wavelengths than induce vitD synthesis (vitD-UVB), Cumulative-weighted UVB dose (CW-D-UVB), Standard deviation (SD), Myeloperoxidase (MPO), Akaike information criterion (AIC), Odds ratio (OR), 95% Confidence interval (95% CI). Table S5. Uni- and multivariable logistic regression analysis of factors associated with AAV phenotype in the combined UKIVAS and RKD cohort, restricted to White participants (sensitivity analysis). Note: OR (95% CI, p). Observations = 2142 (1 missing age). The OR refers to the probability of having MPA-AAV (ref: not MPA) at diagnosis. Model 1 investigates the effect of latitude, adjusted for age at diagnosis and gender. Model 2 investigates the effect of average annual vitD-UVB, adjusted for age at diagnosis and gender. Model 3 investigates the effect of average winter (Dec-Feb) vitD-UVB (2004-2019), adjusted for age at diagnosis and gender. Model 4 investigates the effect of CW-D-UVB at symptom onset, adjusted for age at diagnosis and gender. Cumulative-weighted UVB dose (CW-D-UVB), Standard deviation (SD), Microscopic polyangiitis (MPA), ANCA-associated vasculitis (AAV), Akaike information criterion (AIC), Odds ratio (OR), 95% Confidence interval (95% CI). Supplementary Methods.