Figure 1.
At least 10% of young individuals with CF harbor neutralizing anti-IFNλ2/3 IgG autoAbs. (A) IFNλ1/2/3 neutralization by plasmas from individuals with AD (n = 39), various adults (CT; n = 68), or pwCF (CF; n = 84 samples from n = 51 individuals). Dotted lines indicate thresholds set using standard outlier calculations. Neutralizing plasmas are orange; numbers represent unique individuals; positive individuals are labeled. (B) Anti-IFN-III and anti-IFN-I IgGs in CF plasmas positive (neut; n = 9) or negative (non-neut; n = 6) for IFNλ2/3 neutralization. (C) Spearman’s correlation between IFNλ2/3 neutralization (A) and IgG (B). (D) Anti-IFNλ2/3 IgG subclasses in CF plasmas (n = 5). (E) Area under the curve from PIV5-GFP replication kinetics in A549 cells pretreated with IFNλ2 (or not) in the presence of pwCF plasmas positive (pos) or negative (neg) for IFNλ2/3 neutralization. Values are triplicate means from two experiments. Error bars indicate standard deviations. For the IFNλ2+pos and IFNλ2+neg groups, data are from two patients (squares/triangles) from two experiments. (F) Fluorescence images of infected cells from E. (G) Random forest regression of clinical variables in pwCF positive (n = 4) or negative (n = 16) for anti-IFNλ2/3 autoAbs. Dots represent importance scores per iteration (maximum 5,000); error bars reflect importance spread. Abbreviations: MFI FC, median fluorescence intensity fold-change; IVIG, intravenous immunoglobulin; IBD, inflammatory bowel disease; CFRD, CF-related diabetes; ABPA, allergic bronchopulmonary aspergillosis; SA, Staphylococcus aureus; PA, Pseudomonas aeruginosa. Statistical analyses were two-way ANOVA with the Šidák correction (B), Spearman correlation (C), and Mann–Whitney test (E) (ns, nonsignificant; *P < 0.05; ****P < 0.0001).

At least 10% of young individuals with CF harbor neutralizing anti-IFNλ2/3 IgG autoAbs. (A) IFNλ1/2/3 neutralization by plasmas from individuals with AD (n = 39), various adults (CT; n = 68), or pwCF (CF; n = 84 samples from n = 51 individuals). Dotted lines indicate thresholds set using standard outlier calculations. Neutralizing plasmas are orange; numbers represent unique individuals; positive individuals are labeled. (B) Anti-IFN-III and anti-IFN-I IgGs in CF plasmas positive (neut; n = 9) or negative (non-neut; n = 6) for IFNλ2/3 neutralization. (C) Spearman’s correlation between IFNλ2/3 neutralization (A) and IgG (B). (D) Anti-IFNλ2/3 IgG subclasses in CF plasmas (n = 5). (E) Area under the curve from PIV5-GFP replication kinetics in A549 cells pretreated with IFNλ2 (or not) in the presence of pwCF plasmas positive (pos) or negative (neg) for IFNλ2/3 neutralization. Values are triplicate means from two experiments. Error bars indicate standard deviations. For the IFNλ2+pos and IFNλ2+neg groups, data are from two patients (squares/triangles) from two experiments. (F) Fluorescence images of infected cells from E. (G) Random forest regression of clinical variables in pwCF positive (n = 4) or negative (n = 16) for anti-IFNλ2/3 autoAbs. Dots represent importance scores per iteration (maximum 5,000); error bars reflect importance spread. Abbreviations: MFI FC, median fluorescence intensity fold-change; IVIG, intravenous immunoglobulin; IBD, inflammatory bowel disease; CFRD, CF-related diabetes; ABPA, allergic bronchopulmonary aspergillosis; SA, Staphylococcus aureus; PA, Pseudomonas aeruginosa. Statistical analyses were two-way ANOVA with the Šidák correction (B), Spearman correlation (C), and Mann–Whitney test (E) (ns, nonsignificant; *P < 0.05; ****P < 0.0001).

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