Aicardi–Goutières syndrome – Hydroxychloroquine treatment

The database includes the raw data of the article “Hydroxychloroquine modulates immunological pathways activated by RNA:DNA hybrids in Aicardi–Goutières syndrome patients carrying RNASEH2 mutations”. Aim of the work was to investigate whether hydroxychloroquine (HCQ) is able to modulate the abnormal inflammatory response driven by RNA:DNA hybrids in lymphoblastoid cell lines (LCLs) of Aicardi–Goutières syndrome (AGS) patients.

The database contains data obtained by the following evaluations: i) flow cytometry for the detection of cytosolic RNA:DNA hybrids accumulation; ii) Real-Time PCR for the evaluation of mRNA expression levels of IFIT1 and IFI44, two interferon-stimulated genes ISGs; and of IRF3, MYD88, IRF7 and NF-kB transcripts before and after HCQ treatment; iii) western blot analysis of proteins involved in autophagy (LC3-II/LC3-I ratio and p62) and of cGAS.

We found that RNA:DNA hybrids accumulate mainly in the cytoplasm and co-localize with lysosomes in the LCL derived from an AGS patient carrying a RNASEH2B mutation, suggesting an impairment in the RNA:DNA hybrid degradation. On the other hand, the RNASEH2A-mutant LCL carries RNA:DNA hybrids in endosomes. Moreover, we evidenced that HCQ is a drug that can induce decreased activation of the IFN-α immune cascade only in the RNASEH2B-mutant LCL. Therefore, we hypothesized that HCQ, a European Medicines Agency-approved drug, may be effective in the treatment for AGS mainly when there is an abnormal activation of the innate immune response.