Table 3.

Risk of WNVF or WNVD in subjects carrying auto-Abs neutralizing specific sets of type I IFNs, relative to the general population, with adjustment for age and sex and risk of WNVD by age group

Antitype I IFN auto-Ab (amount of type I IFN neutralized, in plasma diluted 1:10)New cohortOverall cohort
WNV groupOR [95% CI]P valueOR [95% CI]P value
Anti-IFN-ω (100 pg/ml) regardless of other type I IFNs neutralization WNVF 1.6 [0.3–7.8] 0.6 5.8 [3.3–10.1] 5.0 × 10−7 
Anti-IFN-α2 (100 pg/ml) regardless of other type I IFNs neutralization WNVF 0.7 [0.1–11.8] 0.8 5 [2.3–9.9] 1.5 × 10−4 
Anti-IFN-α2 (100 pg/ml) and/or anti-IFN-ω (100 pg/ml) and/or anti-IFN-β (10 ng/ml) WNVF 1.0 [0.2–5.2] 1.0 4.3 [2.6–7.3] 4.1 × 10−6 
Anti-IFN-α2 (100 pg/ml) and/or anti-IFN-ω (100 pg/ml) regardless of anti-IFN-β WNVF 1.12 [0.2–5.6] 0.9 4.7 [2.8–7.9] 1.4 × 10−6 
Anti-IFN-α2 (100 pg/ml) and anti-IFN-ω (100 pg/ml) regardless of anti-IFN-β WNVF 1.6 [0.1–26.4] 0.8 8.7 [4–19.1] 2.1 × 10−5 
Anti-IFN-ω (10 ng/ml) regardless of other type I IFNs neutralization WNVF 2.5 [0.2–39.8] 0.6 12.8 [6–27.5] 1.2 × 10−6 
Anti-IFN-α2 (10 ng/ml) regardless of other type I IFNs neutralization WNVF 2.4 [0.1–39.1] 0.6 12.1 [5.6–26.2] 2 × 10−6 
Anti-IFN-α2 (10 ng/ml) and/or anti-IFN-ω (10 ng/ml) and/or anti-IFN-β (10 ng/ml) WNVF 0.8 [0.1–13.4] 0.9 5.7 [2.9–11.3] 5.3 × 10−5 
Anti-IFN-α2 (10 ng/ml) and/or anti-IFN-ω (10 ng/ml) regardless of anti-IFN-β WNVF 1.5 [0.1–24.4] 0.8 10.0 [5.1–19.8] 4.4 × 10−7 
Anti-IFN-α2 (10 ng/ml) and anti-IFN-ω (10 ng/ml) regardless of anti-IFN-β WNVF 6.2 [0.4–101.9] 0.3 22.5 [9–56.1] 1.8 × 10−6 
Anti-IFN-α2 (10 ng/ml) and anti-IFN-ω (100 pg/ml) regardless of anti-IFN-β WNVF 3.0 [0.2–50.6] 0.5 14.0 [5.7–34] 6.1 × 10−6 
Anti-IFN-ω (100 pg/ml) regardless of other type I IFNs neutralization WNVD (all) 22.6 [16.2–31.2] <10−16 23.4 [18.8–29.3] <10−16 
WNVD ≤65 32 [17–59.9] <10−16 26 [17–39.6] <10−16 
WNVD >65 27.7 [18.3–41.9] <10−16 26.9 [20.4–35.5] <10−16 
Anti-IFN-α2 (100 pg/ml) regardless of other type I IFNs neutralization WNVD (all) 24.5 [17.3–34.5] <10−16 27.2 [21.5–34.4] <10−16 
WNVD ≤65 89.2 [43.9–181.3] <10−16 66.3 [38.1–115.4] <10−16 
WNVD >65 21.8 [14.4–32.8] <10−16 24.7 [18.9–32.4] <10−16 
Anti-IFN-α2 (100 pg/ml) and/or anti-IFN-ω (100 pg/ml) and/or anti-IFN-β (10 ng/ml) WNVD (all) 17.4 [12.7–23.7] <10−16 17.4 [14.1–21.4] <10−16 
WNVD ≤65 27.9 [16.3–47.8] <10−16 19.2 [13.2–27.9] <10−16 
WNVD >65 17.8 [11.9–26.4] <10−16 19 [14.5–24.6] <10−16 
Anti-IFN-α2 (100 pg/ml) and/or anti-IFN-ω (100 pg/ml) regardless of anti-IFN-β WNVD (all) 18.7 [13.8–23.4] <10−16 18.9 [15.4–23.1] <10−16 
WNVD ≤65 36.6 [21.1–63.6] <10−16 24.5 [16.7–36.0] <10−16 
WNVD >65 19.8 [13.4–29.3] <10−16 20.8 [16.2–26.9] <10−16 
Anti-IFN-α2 (100 pg/ml) and anti-IFN-ω (100 pg/ml) regardless of anti-IFN-β WNVD (all) 41.7 [27.9–62.2] <10−16 49.7 [37–67.1] <10−16 
WNVD ≤65 426.4 [114.5–1,587.9] <10−16 300 [106.5–845] <10−16 
WNVD >65 38.3 [24.3–60.2] <10−16 40.5 [29.3–56] <10−16 
Anti-IFN-ω (10 ng/ml) regardless of other type I IFNs neutralization WNVD (all) 52.9 [36–77.5] <10−16 57.1 [43.5–75] <10−16 
WNVD ≤65 162 [75.2–348.8] <10−16 138.9 [81.7–236] <10−16 
WNVD >65 43.7 [28.3–67.4] <10−16 42 [31–57] <10−16 
Anti-IFN-α2 (10 ng/ml) regardless of other type I IFNs neutralization WNVD (all) 51.1 [35–74.4] <10−16 63.1 [48.6–81.8] <10−16 
WNVD ≤65 300.2 [137.4–665.1] <10−16 213.7 [117.6–388.6] <10−16 
WNVD >65 37.4 [24.5–57.2] <10−16 46.9 [35.3–62.3] <10−16 
Anti-IFN-α2 (10 ng/ml) and/or anti-IFN-ω (10 ng/ml) and/or anti-IFN-β (10 ng/ml) WNVD (all) 28.8 [20–41.4] <10−16 31.2 [23.9–40.7] <10−16 
WNVD ≤65 60.3 [30.1–120.8] <10−16 44.4 [26.7–74] <10−16 
WNVD >65 25.8 [16.8–39.9] <10−16 29 [21.2–39.6] <10−16 
Anti-IFN-α2 (10 ng/ml) and/or anti-IFN-ω (10 ng/ml) regardless of anti-IFN-β WNVD (all) 38.4 [27.0–54.6] <10−16 45.6 [36.1–57.6] <10−16 
WNVD ≤65 172.1 [88.9–332.9] <10−16 120.7 [75.5–192.9] <10−16 
WNVD >65 28.8 [19.1–43.2] <10−16 34.8 [26.7–45.3] <10−16 
Anti-IFN-α2 (10 ng/ml) and anti-IFN-ω (10 ng/ml) regardless of anti-IFN-β WNVD (all) 104.6 [66.5–164.4] <10−16 119.7 [83.8–171] <10−16 
WNVD ≤65 548.2 [173.3–1,733.9] <10−16 538.2 [208.1–1,391.8] <10−16 
WNVD >65 80 [49.1–130.5] <10−16 80.8 [55.4–117.8] <10−16 
Anti-IFN-α2 (10 ng/ml) and anti-IFN-ω (100 pg/ml) regardless of anti-IFN-β WNVD (all) 57.2 [34.1–95.8] <10−16 77.5 [50.5–118.9] <10−16 
WNVD ≤65 1,730.9 [92.4–32,443.2] 2.2 × 10−16 1,517 [91.5–25,181.1] <10−16 
WNVD >65 45.2 [26.2–78.1] <10−16 55.3 [35.7–85.5] <10−16 
Anti-IFN-α2 (10 ng/ml) and anti-IFN-ω (10 ng/ml) and anti-IFN-β (10 ng/ml) WNVD (all) 347.7 [18.9–6,381.4] 5.9 × 10−9 173.0 [10.0–3,002.8] 4.9 × 10−10 
WNVD ≤65 200.2 [9.4–4,270.8] 7.9 × 10−5 74.0 [3.5–1,559.6] 9 × 10−4 
WNVD >65 177.2 [9.0–3,497.7] 1.1 × 10−5 116.8 [6.6–2,063.7] 1.1 × 10−7 
Antitype I IFN auto-Ab (amount of type I IFN neutralized, in plasma diluted 1:10)New cohortOverall cohort
WNV groupOR [95% CI]P valueOR [95% CI]P value
Anti-IFN-ω (100 pg/ml) regardless of other type I IFNs neutralization WNVF 1.6 [0.3–7.8] 0.6 5.8 [3.3–10.1] 5.0 × 10−7 
Anti-IFN-α2 (100 pg/ml) regardless of other type I IFNs neutralization WNVF 0.7 [0.1–11.8] 0.8 5 [2.3–9.9] 1.5 × 10−4 
Anti-IFN-α2 (100 pg/ml) and/or anti-IFN-ω (100 pg/ml) and/or anti-IFN-β (10 ng/ml) WNVF 1.0 [0.2–5.2] 1.0 4.3 [2.6–7.3] 4.1 × 10−6 
Anti-IFN-α2 (100 pg/ml) and/or anti-IFN-ω (100 pg/ml) regardless of anti-IFN-β WNVF 1.12 [0.2–5.6] 0.9 4.7 [2.8–7.9] 1.4 × 10−6 
Anti-IFN-α2 (100 pg/ml) and anti-IFN-ω (100 pg/ml) regardless of anti-IFN-β WNVF 1.6 [0.1–26.4] 0.8 8.7 [4–19.1] 2.1 × 10−5 
Anti-IFN-ω (10 ng/ml) regardless of other type I IFNs neutralization WNVF 2.5 [0.2–39.8] 0.6 12.8 [6–27.5] 1.2 × 10−6 
Anti-IFN-α2 (10 ng/ml) regardless of other type I IFNs neutralization WNVF 2.4 [0.1–39.1] 0.6 12.1 [5.6–26.2] 2 × 10−6 
Anti-IFN-α2 (10 ng/ml) and/or anti-IFN-ω (10 ng/ml) and/or anti-IFN-β (10 ng/ml) WNVF 0.8 [0.1–13.4] 0.9 5.7 [2.9–11.3] 5.3 × 10−5 
Anti-IFN-α2 (10 ng/ml) and/or anti-IFN-ω (10 ng/ml) regardless of anti-IFN-β WNVF 1.5 [0.1–24.4] 0.8 10.0 [5.1–19.8] 4.4 × 10−7 
Anti-IFN-α2 (10 ng/ml) and anti-IFN-ω (10 ng/ml) regardless of anti-IFN-β WNVF 6.2 [0.4–101.9] 0.3 22.5 [9–56.1] 1.8 × 10−6 
Anti-IFN-α2 (10 ng/ml) and anti-IFN-ω (100 pg/ml) regardless of anti-IFN-β WNVF 3.0 [0.2–50.6] 0.5 14.0 [5.7–34] 6.1 × 10−6 
Anti-IFN-ω (100 pg/ml) regardless of other type I IFNs neutralization WNVD (all) 22.6 [16.2–31.2] <10−16 23.4 [18.8–29.3] <10−16 
WNVD ≤65 32 [17–59.9] <10−16 26 [17–39.6] <10−16 
WNVD >65 27.7 [18.3–41.9] <10−16 26.9 [20.4–35.5] <10−16 
Anti-IFN-α2 (100 pg/ml) regardless of other type I IFNs neutralization WNVD (all) 24.5 [17.3–34.5] <10−16 27.2 [21.5–34.4] <10−16 
WNVD ≤65 89.2 [43.9–181.3] <10−16 66.3 [38.1–115.4] <10−16 
WNVD >65 21.8 [14.4–32.8] <10−16 24.7 [18.9–32.4] <10−16 
Anti-IFN-α2 (100 pg/ml) and/or anti-IFN-ω (100 pg/ml) and/or anti-IFN-β (10 ng/ml) WNVD (all) 17.4 [12.7–23.7] <10−16 17.4 [14.1–21.4] <10−16 
WNVD ≤65 27.9 [16.3–47.8] <10−16 19.2 [13.2–27.9] <10−16 
WNVD >65 17.8 [11.9–26.4] <10−16 19 [14.5–24.6] <10−16 
Anti-IFN-α2 (100 pg/ml) and/or anti-IFN-ω (100 pg/ml) regardless of anti-IFN-β WNVD (all) 18.7 [13.8–23.4] <10−16 18.9 [15.4–23.1] <10−16 
WNVD ≤65 36.6 [21.1–63.6] <10−16 24.5 [16.7–36.0] <10−16 
WNVD >65 19.8 [13.4–29.3] <10−16 20.8 [16.2–26.9] <10−16 
Anti-IFN-α2 (100 pg/ml) and anti-IFN-ω (100 pg/ml) regardless of anti-IFN-β WNVD (all) 41.7 [27.9–62.2] <10−16 49.7 [37–67.1] <10−16 
WNVD ≤65 426.4 [114.5–1,587.9] <10−16 300 [106.5–845] <10−16 
WNVD >65 38.3 [24.3–60.2] <10−16 40.5 [29.3–56] <10−16 
Anti-IFN-ω (10 ng/ml) regardless of other type I IFNs neutralization WNVD (all) 52.9 [36–77.5] <10−16 57.1 [43.5–75] <10−16 
WNVD ≤65 162 [75.2–348.8] <10−16 138.9 [81.7–236] <10−16 
WNVD >65 43.7 [28.3–67.4] <10−16 42 [31–57] <10−16 
Anti-IFN-α2 (10 ng/ml) regardless of other type I IFNs neutralization WNVD (all) 51.1 [35–74.4] <10−16 63.1 [48.6–81.8] <10−16 
WNVD ≤65 300.2 [137.4–665.1] <10−16 213.7 [117.6–388.6] <10−16 
WNVD >65 37.4 [24.5–57.2] <10−16 46.9 [35.3–62.3] <10−16 
Anti-IFN-α2 (10 ng/ml) and/or anti-IFN-ω (10 ng/ml) and/or anti-IFN-β (10 ng/ml) WNVD (all) 28.8 [20–41.4] <10−16 31.2 [23.9–40.7] <10−16 
WNVD ≤65 60.3 [30.1–120.8] <10−16 44.4 [26.7–74] <10−16 
WNVD >65 25.8 [16.8–39.9] <10−16 29 [21.2–39.6] <10−16 
Anti-IFN-α2 (10 ng/ml) and/or anti-IFN-ω (10 ng/ml) regardless of anti-IFN-β WNVD (all) 38.4 [27.0–54.6] <10−16 45.6 [36.1–57.6] <10−16 
WNVD ≤65 172.1 [88.9–332.9] <10−16 120.7 [75.5–192.9] <10−16 
WNVD >65 28.8 [19.1–43.2] <10−16 34.8 [26.7–45.3] <10−16 
Anti-IFN-α2 (10 ng/ml) and anti-IFN-ω (10 ng/ml) regardless of anti-IFN-β WNVD (all) 104.6 [66.5–164.4] <10−16 119.7 [83.8–171] <10−16 
WNVD ≤65 548.2 [173.3–1,733.9] <10−16 538.2 [208.1–1,391.8] <10−16 
WNVD >65 80 [49.1–130.5] <10−16 80.8 [55.4–117.8] <10−16 
Anti-IFN-α2 (10 ng/ml) and anti-IFN-ω (100 pg/ml) regardless of anti-IFN-β WNVD (all) 57.2 [34.1–95.8] <10−16 77.5 [50.5–118.9] <10−16 
WNVD ≤65 1,730.9 [92.4–32,443.2] 2.2 × 10−16 1,517 [91.5–25,181.1] <10−16 
WNVD >65 45.2 [26.2–78.1] <10−16 55.3 [35.7–85.5] <10−16 
Anti-IFN-α2 (10 ng/ml) and anti-IFN-ω (10 ng/ml) and anti-IFN-β (10 ng/ml) WNVD (all) 347.7 [18.9–6,381.4] 5.9 × 10−9 173.0 [10.0–3,002.8] 4.9 × 10−10 
WNVD ≤65 200.2 [9.4–4,270.8] 7.9 × 10−5 74.0 [3.5–1,559.6] 9 × 10−4 
WNVD >65 177.2 [9.0–3,497.7] 1.1 × 10−5 116.8 [6.6–2,063.7] 1.1 × 10−7 

≤65 and >65 indicate age cutoffs, in years; anti-IFN-ω and anti-IFN-α2 indicate auto-Abs neutralizing IFN-ω or IFN-α2, respectively, regardless of their effects on other type I IFNs.

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