DOI: 10.5061/dryad.cfxpnvxg3
title: Multi-omics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature

description: 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 patients share common immunopathological mechanisms, while some
 abnormalities are typical of the different clinical phenotypes and could
 help improve the diagnosis and clinical management of RAG patients. Please
 see GEO accession GSE274284 for the associated CITEseq data. 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.
description: 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.
description: # 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 **Description:** Relative fluorescence values from the Somascan assay. See file SomalogicPanelMetadata.csv for full info on the variable columns. ##### Variables * SampleID: Coded sample ID matching publication supplementary tables * TimePoint: NA * Group: Class of RAG mutation or Control * Subject: Similar to sample ID * STUB1: Gene symbol; Relative fluorescence units * CEBPB: Gene symbol; Relative fluorescence units * ENO2: Gene symbol; Relative fluorescence units * PIAS4: Gene symbol; Relative fluorescence units * IL10RA: Gene symbol; Relative fluorescence units * STAT3: Gene symbol; Relative fluorescence units * IRF1: Gene symbol; Relative fluorescence units * JUN: Gene symbol; Relative fluorescence units * MCL1: Gene symbol; Relative fluorescence units * OAS1: Gene symbol; Relative fluorescence units * MYC: Gene symbol; Relative fluorescence units * SMAD3: Gene symbol; Relative fluorescence units * SMAD2: Gene symbol; Relative fluorescence units * IL12B.IL23A: Gene symbol; Relative fluorescence units * PDGFRA: Gene symbol; Relative fluorescence units * IL12A.IL12B: Gene symbol; Relative fluorescence units * STAT1: Gene symbol; Relative fluorescence units * STAT6: Gene symbol; Relative fluorescence units * LRRK2: Gene symbol; Relative fluorescence units * BGLAP: Gene symbol; Relative fluorescence units * IL5: Gene symbol; Relative fluorescence units * GPD1: Gene symbol; Relative fluorescence units * IGHA1.IGHA2: Gene symbol; Relative fluorescence units * CLC: Gene symbol; Relative fluorescence units * N6AMT1: Gene symbol; Relative fluorescence units * PDXK: Gene symbol; Relative fluorescence units * TLR4: Gene symbol; Relative fluorescence units * REG4: Gene symbol; Relative fluorescence units * HSPB1: Gene symbol; Relative fluorescence units * CHI3L1: Gene symbol; Relative fluorescence units * ENO1: Gene symbol; Relative fluorescence units * APOL1: Gene symbol; Relative fluorescence units * CD38: Gene symbol; Relative fluorescence units * CD59: Gene symbol; Relative fluorescence units * FABP1: Gene symbol; Relative fluorescence units * GDF11: Gene symbol; Relative fluorescence units * BTC: Gene symbol; Relative fluorescence units * HIF1A: Gene symbol; Relative fluorescence units * S100A6: Gene symbol; Relative fluorescence units * SECTM1: Gene symbol; Relative fluorescence units * RSPO3: Gene symbol; Relative fluorescence units * REG1A: Gene symbol; Relative fluorescence units * BCL2L2: Gene symbol; Relative fluorescence units * FIGF: Gene symbol; Relative fluorescence units * SOST: Gene symbol; Relative fluorescence units * FAM3D: Gene symbol; Relative fluorescence units * CSH1.CSH2: Gene symbol; Relative fluorescence units * EFNB1: Gene symbol; Relative fluorescence units * SNAP25: Gene symbol; Relative fluorescence units * LYPD3: Gene symbol; Relative fluorescence units * NEGR1: Gene symbol; Relative fluorescence units * BCL6: Gene symbol; Relative fluorescence units * FSTL1: Gene symbol; Relative fluorescence units * SPP1: Gene symbol; Relative fluorescence units * LUM: Gene symbol; Relative fluorescence units * CD177: Gene symbol; Relative fluorescence units * CHKB: Gene symbol; Relative fluorescence units * SMOC1: Gene symbol; Relative fluorescence units * SERPINA10: Gene symbol; Relative fluorescence units * FLRT2: Gene symbol; Relative fluorescence units * FLRT3: Gene symbol; Relative fluorescence units * ISLR2: Gene symbol; Relative fluorescence units * VTN: Gene symbol; Relative fluorescence units * DSC2: Gene symbol; Relative fluorescence units * LDLR: Gene symbol; Relative fluorescence units * HK2: Gene symbol; Relative fluorescence units * HK1: Gene symbol; Relative fluorescence units * SEMA5A: Gene symbol; Relative fluorescence units * LTBP4: Gene symbol; Relative fluorescence units * PIANP: Gene symbol; Relative fluorescence units * ADM: Gene symbol; Relative fluorescence units * S100A4: Gene symbol; Relative fluorescence units * RNF43: Gene symbol; Relative fluorescence units * TNFRSF10D: Gene symbol; Relative fluorescence units * ZNRF3: Gene symbol; Relative fluorescence units * C10orf54: Gene symbol; Relative fluorescence units * EFNA2: Gene symbol; Relative fluorescence units * APOM: Gene symbol; Relative fluorescence units * IFNB1: Gene symbol; Relative fluorescence units * IFNA10: Gene symbol; Relative fluorescence units * IFNA7: Gene symbol; Relative fluorescence units * EFNB2: Gene symbol; Relative fluorescence units * HHLA2: Gene symbol; Relative fluorescence units * IL1R2: Gene symbol; Relative fluorescence units * AMIGO2: Gene symbol; Relative fluorescence units * RXFP1: Gene symbol; Relative fluorescence units * CD93: Gene symbol; Relative fluorescence units * NRG4: Gene symbol; Relative fluorescence units * HIST2H2BE: Gene symbol; Relative fluorescence units * HIST3H2A: Gene symbol; Relative fluorescence units * HIST1H3A: Gene symbol; Relative fluorescence units * IFNG: Gene symbol; Relative fluorescence units * IL36B: Gene symbol; Relative fluorescence units * IL36A: Gene symbol; Relative fluorescence units * ISG15: Gene symbol; Relative fluorescence units * EFNA3: Gene symbol; Relative fluorescence units * YWHAB: Gene symbol; Relative fluorescence units * YWHAE: Gene symbol; Relative fluorescence units * ANXA5: Gene symbol; Relative fluorescence units * MSTN: Gene symbol; Relative fluorescence units * HCE001796: Hybridization Control; Relative fluorescence units * HCE003167: Hybridization Control; Relative fluorescence units * C4A.C4B: Gene symbol; Relative fluorescence units * F11: Gene symbol; Relative fluorescence units * CCL27: Gene symbol; Relative fluorescence units * HCE000414: Hybridization Control; Relative fluorescence units * COL18A1: Gene symbol; Relative fluorescence units * TIMP1: Gene symbol; Relative fluorescence units * PLAT: Gene symbol; Relative fluorescence units * HCE003183: Gene symbol; Relative fluorescence units * PROK1: Gene symbol; Relative fluorescence units * HCE004333: Hybridization Control; Relative fluorescence units * HCE004359: Hybridization Control; Relative fluorescence units * TIMP2: Gene symbol; Relative fluorescence units * HCE004331: Hybridization Control; Relative fluorescence units * HCE003300: Hybridization Control; Relative fluorescence units * HCE000483: Hybridization Control; Relative fluorescence units * TGFB1: Gene symbol; Relative fluorescence units * FLT4: Gene symbol; Relative fluorescence units * HCE004152: Hybridization Control; Relative fluorescence units * C5: Gene symbol; Relative fluorescence units * APOE: Gene symbol; Relative fluorescence units * BDNF: Gene symbol; Relative fluorescence units * C8A.C8B.C8G: Gene symbol; Relative fluorescence units * HCE000342: Hybridization Control; Relative fluorescence units * CTSG: Gene symbol; Relative fluorescence units * CXCL16: Gene symbol; Relative fluorescence units * FGF10: Gene symbol; Relative fluorescence units * FGF8: Gene symbol; Relative fluorescence units * PLA2G2E: Gene symbol; Relative fluorescence units * PLA2G5: Gene symbol; Relative fluorescence units * CCL20: Gene symbol; Relative fluorescence units * APCS: Gene symbol; Relative fluorescence units * KIT: Gene symbol; Relative fluorescence units * TIMP3: Gene symbol; Relative fluorescence units * ANGPT4: Gene symbol; Relative fluorescence units * CDH1: Gene symbol; Relative fluorescence units * GFRA3: Gene symbol; Relative fluorescence units * HCE000104: Hybridization Control; Relative fluorescence units * EFNB3: Gene symbol; Relative fluorescence units * GFRA2: Gene symbol; Relative fluorescence units * CCL21: Gene symbol; Relative fluorescence units * HMGB1: Gene symbol; Relative fluorescence units * TNFRSF11B: Gene symbol; Relative fluorescence units * POMC: Gene symbol; Relative fluorescence units * CFI: Gene symbol; Relative fluorescence units * IGFBP3: Gene symbol; Relative fluorescence units * CCL2: Gene symbol; Relative fluorescence units * MMP9: Gene symbol; Relative fluorescence units * MPO: Gene symbol; Relative fluorescence units * PRL: Gene symbol; Relative fluorescence units * VEGFA: Gene symbol; Relative fluorescence units * TNFRSF9: Gene symbol; Relative fluorescence units * TNFSF9: Gene symbol; Relative fluorescence units * ANGPT2: Gene symbol; Relative fluorescence units * CD80: Gene symbol; Relative fluorescence units * TNFRSF8: Gene symbol; Relative fluorescence units * CRLF1.CLCF1: Gene symbol; Relative fluorescence units * CST3: Gene symbol; Relative fluorescence units * TYRO3: Gene symbol; Relative fluorescence units * EIF5: Gene symbol; Relative fluorescence units * EFNA4: Gene symbol; Relative fluorescence units * EFNA5: Gene symbol; Relative fluorescence units * ERBB2: Gene symbol; Relative fluorescence units * ERBB3: Gene symbol; Relative fluorescence units * ERBB4: Gene symbol; Relative fluorescence units * TACSTD2: Gene symbol; Relative fluorescence units * IL6ST: Gene symbol; Relative fluorescence units * HMOX2: Gene symbol; Relative fluorescence units * Human.virus: HPV E7 Type 16; Relative fluorescence units * Human.virus.1: HPV E7 Type18; Relative fluorescence units * HSP90AA1.HSP90AB1: Gene symbol; Relative fluorescence units * IL1RAP: Gene symbol; Relative fluorescence units * IL10RB: Gene symbol; Relative fluorescence units * IL12RB1: Gene symbol; Relative fluorescence units * IL13RA1: Gene symbol; Relative fluorescence units * IL2RG: Gene symbol; Relative fluorescence units * LAYN: Gene symbol; Relative fluorescence units * LTBR: Gene symbol; Relative fluorescence units * MRC1: Gene symbol; Relative fluorescence units * CSF1R: Gene symbol; Relative fluorescence units * MST1R: Gene symbol; Relative fluorescence units * PAFAH1B2: Gene symbol; Relative fluorescence units * CDH3: Gene symbol; Relative fluorescence units * PRKCA: Gene symbol; Relative fluorescence units * PRKCZ: Gene symbol; Relative fluorescence units * GDI2: Gene symbol; Relative fluorescence units * ICAM3: Gene symbol; Relative fluorescence units * PLAUR: Gene symbol; Relative fluorescence units * TNFRSF1A: Gene symbol; Relative fluorescence units * NTRK3: Gene symbol; Relative fluorescence units * TNFRSF17: Gene symbol; Relative fluorescence units * DCN: Gene symbol; Relative fluorescence units * CAPN1.CAPNS1: Gene symbol; Relative fluorescence units * CKM: Gene symbol; Relative fluorescence units * EGFR: Gene symbol; Relative fluorescence units * HGF: Gene symbol; Relative fluorescence units * HSPD1: Gene symbol; Relative fluorescence units * C3: Gene symbol; Relative fluorescence units * IGFBP5: Gene symbol; Relative fluorescence units * IGFBP6: Gene symbol; Relative fluorescence units * MIA: Gene symbol; Relative fluorescence units * PLA2G2A: Gene symbol; Relative fluorescence units * OSM: Gene symbol; Relative fluorescence units * PECAM1: Gene symbol; Relative fluorescence units * PSPN: Gene symbol; Relative fluorescence units * PF4: Gene symbol; Relative fluorescence units * PROS1: Gene symbol; Relative fluorescence units * TNFRSF13B: Gene symbol; Relative fluorescence units * CCL25: Gene symbol; Relative fluorescence units * SERPINA7: Gene symbol; Relative fluorescence units * TNFSF18: Gene symbol; Relative fluorescence units * CNTFR: Gene symbol; Relative fluorescence units * AIMP1: Gene symbol; Relative fluorescence units * EPOR: Gene symbol; Relative fluorescence units * CSF3R: Gene symbol; Relative fluorescence units * IL37: Gene symbol; Relative fluorescence units * LAMA1.LAMB1..LAMC1: Gene symbol; Relative fluorescence units * MICA: Gene symbol; Relative fluorescence units * POR: Gene symbol; Relative fluorescence units * NANOG: Gene symbol; Relative fluorescence units * NCR2: Gene symbol; Relative fluorescence units * NOV: Gene symbol; Relative fluorescence units * SIGLEC6: Gene symbol; Relative fluorescence units * SIGLEC7: Gene symbol; Relative fluorescence units * SHH: Gene symbol; Relative fluorescence units * IGHG1.IGHG2.IGHG3.IGHG4.IGK..IGL.: Gene symbol; Relative fluorescence units * CRLF2: Gene symbol; Relative fluorescence units * ULBP3: Gene symbol; Relative fluorescence units * INHBA: Gene symbol; Relative fluorescence units * APOA1: Gene symbol; Relative fluorescence units * AZU1: Gene symbol; Relative fluorescence units * GDF5: Gene symbol; Relative fluorescence units * C1QA.C1QB..C1QC: Gene symbol; Relative fluorescence units * C3.1: Gene symbol; Relative fluorescence units * C3.2: Gene symbol; Relative fluorescence units * FAM107A: Gene symbol; Relative fluorescence units * FGF18: Gene symbol; Relative fluorescence units * FGF19: Gene symbol; Relative fluorescence units * FGF20: Gene symbol; Relative fluorescence units * FGF9: Gene symbol; Relative fluorescence units * GDF11.MSTN: Gene symbol; Relative fluorescence units * HPX: Gene symbol; Relative fluorescence units * Human.virus.2: Gene symbol; Relative fluorescence units * CCL1: Gene symbol; Relative fluorescence units * IGFBP1: Gene symbol; Relative fluorescence units * IL10: Gene symbol; Relative fluorescence units * IL16: Gene symbol; Relative fluorescence units * IL17F: Gene symbol; Relative fluorescence units * IL22: Gene symbol; Relative fluorescence units * LTF: Gene symbol; Relative fluorescence units * CCL4L1: Gene symbol; Relative fluorescence units #### File: SomalogicPanelMetadata.csv **Description:**  Additional info on the variables present in Somascan.csb. ##### Variables * SeqId: Somalogic identifier * SeqIdVersion: Somalogic identifier version * SomaId: Somamer identifier * TargetFullName: Name of assay target * Target: Abbreviated name of assay target * UniProt: Uniprot database ID * EntrezGeneID: Entrez database ID, if available * EntrezGeneSymbol: Entrez gene symbol, if available * Organism: target organism * Units: RFU, relative fluorescence units * Type: Analyte type ## Access information Data was derived from the following sources: * Somalogic proteomic platform