Multi-omics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature

Human RAG deficiency may manifest with distinct clinical and immunological phenotypes. By applying a multi-omics approach to a large group of RAG-mutant patients, we aimed to characterize the immunopathology associated with various forms of RAG deficiency. Defective T and B cell development has been observed in all phenotypes; however, patients with RAG deficiency due to hypomorphic mutations can generate T and B cells with signatures of immune dysregulation and production of autoantibodies to a broad range of self-antigens, including type I interferons. TH2 skewing and a prominent inflammatory signature characterize Omenn syndrome, whereas leaky forms of RAG deficiency are associated with a TH1 profile both in blood and in tissues. CITE-seq analysis helped define the cell lineage-specific contribution to the distinct immunopathology associated with human RAG deficiency phenotypes, opening perspectives for targeted pharmacological interventions. Our results show that all RAG-mutant pati..., SOMAscan (SomaLogic) was used to measure 1,305 human protein analytes in plasma from 20 RAG patients (5 each for the CID, LS, OS, and SCID groups) and 12 healthy donors. Sample data were normalized to remove hybridization variation within a run. Overall scaling was performed on a per-plate basis to remove overall intensity differences between runs. This was followed by median normalization across the different sample types to remove other assay biases within the run., , # Multi-omics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature

[https://doi.org/10.5061/dryad.cfxpnvxg3](https://doi.org/10.5061/dryad.cfxpnvxg3)

## Description of the data and file structure

In the deposited dataset, SOMAscan (SomaLogic) was used to measure 1,305 human protein analytes in plasma from 20 RAG patients (5 each for the CID, LS, OS, and SCID groups) and 12 HD. Data are normalized relative fluorescence units from the SOMAscan platform, presented in comma-separated values. The columns represent the measured proteins, with the different serum samples in the rows; the first 4 columns describe the samples, with the \"Group\" corresponding to the disease groups presented in the publication (healthy controls in different age groups: CID = Combined Immunodeficiency, SCID = Severe Combined Immunodeficiency, OS = Omenn Syndrome, LS = Leaky SCID). 

### Files and variables

#### File: Somascan.csv

**Descripti...