{
  "abstract": "Objectives There is a link between the number of X chromosomes and SLE risk.The disease is more common in women (XX) than in men (XY), and the risk increases in patients with triple X (XXX) and Klinefelter (XXY) syndromes and decreases in Turner syndrome (X0). The mechanisms behind this observation remain unclear.In females, one X chromosome is randomly silenced by XIST, a long noncoding RNA.We hypothesize that abnormal X chromosome inactivation (XCI) or increased escape from X inactivation, leading to biallelic gene expression, may contribute to SLE and to its higher prevalence in women.Methods We studied children and adults with SLE (n=37), who fulfilled the 2019 ACR/EULAR SLE criteria, 54% with lupus nephritis (20/37), and healthy controls (n=29).Monocytes, B lymphocytes, CD4+ and CD8+ T lymphocytes were isolated by cell sorting.XIST was quantified by RT-qPCR.To evaluate the preferential inactivation of one of the two X chromosomes, we used the HUMARA assay and pyrosequencing with the SNIPs XIST rs16 and XIST rs18.Results 1) XIST was overexpressed in SLE patients compared to healthy controls in all cells studied. This difference was statistically significant for B lymphocytes (p=0.008) and CD4+ T lymphocytes (p=0.044).2) XIST expression was four times higher in monocytes of patients with lupus nephritis than in patients without renal involvement. Moreover, XIST expression was significantly increased in monocytes of patients with active lupus nephritis compared with patients with inactive lupus nephritis (p=0.020).3) HUMARA assay, non-random XCI (>=70%) was more common in SLE patients than in healthy controls. In CD4+ T lymphocytes, 43% of SLE patients and 15% of controls showed preferential inactivation of one of the X chromosomes. In B lymphocytes, 32% of SLE patients and 8% of controls had a preferential inactivation. Skewing ratios >80% were only detected in SLE patients.Pyrosequencing method in B lymphocytes, the controls were all randomly inactivated, and preferential inactivation was found in 27% of SLE patients with the SNIP XIST rs16 and 11% with the SNIP XIST rs18.Conclusions These results highlight the potential involvement of XCI in the pathogenesis of SLE and lupus nephritis.",
  "authors": [
    {
      "affiliations": [
        "GIMM Gulbenkian Institute for Molecular Medicine, Lisboa, Portugal"
      ],
      "name": "Joana Inácio"
    },
    {
      "affiliations": [
        "GIMM Gulbenkian Institute for Molecular Medicine, Lisboa, Portugal"
      ],
      "name": "Adriana Vieira"
    },
    {
      "affiliations": [
        "GIMM Gulbenkian Institute for Molecular Medicine, Lisboa, Portugal",
        "Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal"
      ],
      "name": "Inês Almada Correia"
    },
    {
      "affiliations": [
        "Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal"
      ],
      "name": "Beatriz Graça"
    },
    {
      "affiliations": [
        "Unidade de Genética Molecular Centro de Genética Médica Dr. Jacinto Magalhães, Porto, Portugal"
      ],
      "name": "Ema Neves"
    },
    {
      "affiliations": [
        "Unidade de Genética Molecular Centro de Genética Médica Dr. Jacinto Magalhães, Porto, Portugal",
        "UMIB Unit for Multidisciplinary Research in Biomedicine ICBAS Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal",
        "ITR Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal"
      ],
      "name": "Paula Jorge"
    },
    {
      "affiliations": [
        "GIMM Gulbenkian Institute for Molecular Medicine, Lisboa, Portugal"
      ],
      "name": "Helena Nunes-Cabaço"
    },
    {
      "affiliations": [
        "Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal",
        "Serviço de Reumatologia e Doenças Ósseas Metabólicas Hospital de Santa Maria ULS Santa Maria, Lisboa, Portugal"
      ],
      "name": "Nikita Khmelinskii"
    },
    {
      "affiliations": [
        "Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal",
        "Serviço de Reumatologia Hospital Garcia de Orta Unidade Local de Saúde de Almada-Seixal, Almada, Portugal"
      ],
      "name": "Maria José Santos"
    },
    {
      "affiliations": [
        "iBB-Institute for Bioengineering and Biosciences and Department of Bioengineering Instituto Superior Técnico, Lisboa, Portugal",
        "Associate Laboratory i4HB Institute for Health and Bioeconomy Instituto Superior Técnico, Lisboa, Portugal"
      ],
      "name": "Simão Teixeira Da Rocha"
    },
    {
      "affiliations": [
        "GIMM Gulbenkian Institute for Molecular Medicine, Lisboa, Portugal",
        "Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal",
        "Unidade de Reumatologia Pediátrica Departamento de Pediatria Hospital de Santa Maria ULS Santa Maria, Lisboa, Portugal"
      ],
      "name": "Patrícia Costa-Reis"
    }
  ],
  "title": "PT1:05 X-chromosome inactivation in systemic lupus erythematosus: results from the X-lupus study",
  "uid": "e1762c51-60c7-5cc6-afce-301e031e3b59"
}