{
  "abstract": "Objectives Primary antiphospholipid syndrome (pAPS) is an autoimmune disease that, unlike other autoimmune diseases, commonly presents with thrombotic events rather than inflammatory manifestations. A peripheral type I interferon (IFN) signature distinguishes patients with pAPS from healthy individuals, but its broader molecular landscape compared with other autoimmune diseases remains unknown.Methods Whole blood RNA sequencing from patients with pAPS (n=83), systemic lupus erythematosus (SLE; n=249), Sjögren’s disease (SjD; n=253), systemic sclerosis (SSc; n=247), and from 497 matched healthy controls (HC) from the PRECISESADS project . We applied supervised pathway enrichment analysis, unsupervised weighted gene co-expression network analysis (WGCNA), and deconvolution analysis to characterise the molecular profiles of pAPS.Results A total of 85 upregulated and 10 downregulated differentially expressed genes (DEGs) were detected in pAPS compared with HC, indicating an overall upregulation of type I and II IFN signalling, complement cascade, and coagulation in pAPS, coupled with differentially enriched neutrophil degranulation and monocyte chemotaxis pathways. However, only 15 of those genes were uniquely differentially expressed in patients with pAPS across the investigated autoimmune diseases. The comparison between pAPS and SLE revealed 334 DEGs (71 up- and 263 downregulated). Enrichment analysis revealed downregulation of type I/II IFN signalling and complement pathways in pAPS versus SLE. Moreover, type I and II IFN signalling was significantly downregulated in pAPS compared to SjD or SSc. WGCNA identified 19 modules of co-expressed genes, with pAPS strongly linked only to upregulation of the ‘IFN’ module compared to HC. However, the upregulation of the ‘IFN’ gene module was more pronounced in SLE, SjD, and SSc compared with pAPS, supporting a gradience in the upregulation of IFN-related genes across these diseases. Within pAPS, a history of miscarriages was positively associated with the ‘methylation’ gene module, while thrombocytopenia was negatively associated with the ‘T cell’ gene modules. Deconvolution analysis showed that patients with pAPS exhibited significant alterations in proportions of neutrophils, NK, naïve T, and memory T cells compared to HC.Conclusions PAPS exhibit a distinct molecular profile within the spectrum of autoimmune diseases, marked by a modest activation of interferon signalling, less pronounced than the interferon signalling seen in SLE, SSc, or SjD.",
  "authors": [
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Dionysis Nikolopoulos"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Konstantinos Charitidis"
    },
    {
      "affiliations": [
        "Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milano, Italy"
      ],
      "name": "Lorenzo Beretta"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Julius Lindblom"
    },
    {
      "affiliations": [
        "GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada/Andalusian Regional Government, Granada, Spain"
      ],
      "name": "Guillermo Barturen"
    },
    {
      "affiliations": [
        "GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada/Andalusian Regional Government, Granada, Spain"
      ],
      "name": "Marta E Alarcón-Riquelme"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Ioannis Parodis"
    }
  ],
  "title": "S8:04 Less pronounced interferon signature in primary antiphospholipid syndrome compared with other autoimmune diseases",
  "uid": "70f61114-512b-58c1-9680-34ad33ba96b8"
}