The review by Hale provides a broad and comprehensive overview of the field of auto-Abs against type I interferons.

It is really an excellent, well organized and easy to read summary of (i) the impact of these auto-Abs to type I IFNs on viral disease, (ii) the known genetic and non-genetic etiologies underlying the occurrence of these auto-abs and (iii) the potential hypothesis linking a predisposition in some individual and the occurrence of these auto-Abs to type I IFNs.

The review is very interesting, and the references are really complete.

Abstract is very good. Figures are simple, and very nice.

I have only one comment:
- I would perhaps distinguish auto-Abs to IFN-beta from auto-Abs to IFNa2 and IFNw, as (i) refs 40-42 (on HLA) refers to IFNbeta (line 135) and (ii) APS1 patients rarely harbor anti-IFNb auto-Abs (line 159)

Here are a few other minor suggestions:
- Line 52: I would add “production” to say “production or response”
- Line 87: it could be added that there is a small decrease of the prevalence after 85 years of age
- Lines 90-97: maybe add the % of prevalence in the different diseases?
- Line 198-200: there is also a decrease of IFN production with age
- Lines 247-265: another argument would be to say that these are high affinity IgG auto-Abs, that lead to severe infection days after YFV vaccination which makes it virtually almost certain that they precede infection (ref
- Line 276: these auto-Abs were also found in mucosa (Lopez et al., JEM, 2021 for example)
- In terms of treatment options: IFNlambda now seems like a good option (https://www.nejm.org/doi/full/10.1056/NEJMoa2209760).

Honestly, this is one of the best reviews I have read on the type I IFN auto-Abs.

Congratulations to the author.

The author has well responded to my comments, and I have no further requests.