{
  "abstract": "Objectives Interleukin 16 (IL16) is important in pathogenesis of SLE, particulary in T-cell migration. CD4 is considered to be its primary receptor. CD9, a surface protein of tetraspanin family, was suggested as an alternative receptor. Therefore we aimed to map CD9 expression in circulating lymphocytes in active SLE (A-SLE) patients, explore its clinical relevance, and examine hypothesis if IL16 mediates cell migration via CD9.Methods Study included 22 A-SLE patients, (9 with lupus nephritis (LN)) and 8 healthy controls (HC). Lymphocytes were phenotyped and analyzed for CD9 expression by multiparameter flow cytometry. Serum and urine IL16 levels were measured. Findings were compared across LN, non-LN and HC. Disease activity was assessed by SLEDAI-2K. Migratory experiments were performed with lymphocytes from A-SLE and HC.Results Proportions of CD9+CD4+ and CD9+CD8+cells were decreased, whereas CD9+B cells were increased in A-SLE in comparison to HC. Zooming in the CD4+T subsets in A-SLE, reductions of CD9+ cells were observed within Treg, Th1, Th2, and Th17 compartments. NK and NKT cell frequencies did not differ.Detailed analysis of CD9+CD8+T cells showed decreased frequencies of CD9+naïve (TN) cells in both LN and non-LN patients, and lower proportions of CD9+ effector memory RA (TEMRA) cells in non-LN. In contrast, LN patients exhibited the highest proportions of CD9+ central memory (TCM) cells. In B-cell subpopulation analysis revealed that LN patients had increased frequencies of CD9+cells among double-negative (DN), DN1, DN3 subsets and resting naïve subsets.Importantly, frequencies of CD9+ cells in LN patients across multiple subsets correlated positively with disease activity (SLEDAI-2K; r =0.5 or higher, p < 0.05 or lower). Association was absent in non-LN.Migration assays demonstrated that IL16 induced recruitment of both CD4+ and CD8+T cells, but CD8+T-cell migration was more pronoun in patients than HC (p<0.05). Intriguingly, these migratory lupus CD8+T cells highly expressed CD9, suggesting the interactive role between CD9 and IL16 in promoting A-SLE CD8+T migration.Conclusions CD9+ expression is markedly altered across multiple immune cell subsets in active SLE. Our findings suggest that IL16 may drive differential recruitment of CD9+T cells and preferentially recruit CD8+T cells in SLE, potentially contributing to disease-specific immune dysregulation.",
  "authors": [
    {
      "affiliations": [
        "Centre for Rheumatology, Academic Specialist Centre, Stockholm, Sweden"
      ],
      "name": "Vilija Oke"
    },
    {
      "affiliations": [
        "Centre for Rheumatology, Academic Specialist Centre, Stockholm, Sweden",
        "Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Kittikorn Wangriatisak"
    },
    {
      "affiliations": [
        "Medicine Unit Dermatology, Gastroenterology, Rheumatology, Section of Rheumatology, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Francesca Faustini"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Vivianne Malmström"
    },
    {
      "affiliations": [
        "Medicine Unit Dermatology, Gastroenterology, Rheumatology, Section of Rheumatology, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Iva Gunnarsson"
    }
  ],
  "title": "PO:06:162 Altered CD9+ Expression in SLE immune cells could be related to IL-16–mediated T-cell recruitment",
  "uid": "1c1bf001-26ef-50bc-bdcc-9bee069d1bc6"
}