{
  "abstract": "Objectives To characterize real-world data describing the genetic landscape, clinical phenotype, and outcomes of a monogenic lupus cohort.Methods In this nationwide study, we evaluated all genetically confirmed monogenic lupus patients across Türkiye. Clinical, laboratory, treatment, and outcome data were compared between groups defined by pathogenic variants in distinct pathways.Results A total of 88 patients were included. Genetic analysis revealed complement pathway deficiencies in 28 patients (31.8%). Defects in nucleic acid metabolism and clearance constituted the largest subgroup, observed in 36 patients (40.9%), predominantly involving DNASE1L3 and TREX1. Type I interferon signaling and regulation defects were detected in 6 patients (6.8%), including DDX58, IFIH1, ADAR, IRF5, and IRAK1. Defects in immune regulation and lymphocyte signaling were identified in 17 patients (19.3%), involving genes associated with immune tolerance and JAK–STAT dysregulation such as ACP5, PRKCD/PRKCQ, STAT3 gain-of-function, SOCS1, SHOC2, ZAP70, RAG1, HDAC7, FOXP3, and RELA. Consanguinity was reported in 56 patients (63.6%), and a positive family history in 34 (38.6%). Antinuclear antibodies were positive in 66 patients (75%) and anti-dsDNA in 33 (37.5%). Hypocomplementemia was present in 56 patients (63.6%). Clinically, mucocutaneous involvement predominated, particularly acute cutaneous manifestations (61.3%), followed by hematologic involvement (44.3%), arthritis (37.5%), and renal disease (35.2%). Lupus nephritis occurred in 31 patients (35.2%), with class IV nephritis being the most frequent histopathological subtype (32%). Neurological manifestations not captured by current classification criteria were observed in 18 patients (20.4%), including spasticity, Babinski sign, hyperreflexia, developmental delay, and encephalitis. Pulmonary involvement occurred in 21.6%, and intracranial calcifications were detected in 13.6%. Vasculopathic features were common, including Raynaud phenomenon (n=22, 25%), chilblain lesions (n=18, 20.4%), livedo (n=18, 20.4%), and palmar–plantar erythema (n=19, 21.5%). Most patients (n= 77, 87.5%) required corticosteroid therapy. JAK inhibitors were used in 29 patients (33%); response was complete in 3, partial in 21, and absent in 5, while 2 patients developed severe infections. At the last follow-up, 47 patients (53.4%) had a PedSDI score of at least 1, indicating substantial cumulative organ damage. Seven patients died during follow-up.Conclusions This largest monogenic lupus cohort demonstrates atypical neurological, vasculopathic, and immunodeficiency-related features and a high burden of cumulative organ damage.",
  "authors": [
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Istanbul, Turkey"
      ],
      "name": "Sezgin Sahin"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Istanbul, Turkey"
      ],
      "name": "Nergis Akay"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, Istanbul, Turkey"
      ],
      "name": "Sıla Atamyıldız Ucar"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Cukurova University Faculty of Medicine, Adana, Turkey"
      ],
      "name": "Aybuke Alisan"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, Istanbul, Turkey"
      ],
      "name": "Eray Tunce"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Erciyes University Faculty of Medicine, Kayseri, Turkey"
      ],
      "name": "Eda Kayhan"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara, Turkey"
      ],
      "name": "Yasemin Ugur Es"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, University of Health Sciences, Etlik City Hospital, Ankara, Turkey"
      ],
      "name": "Aysenur Alkaya"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Istanbul University Faculty of Medicine, Istanbul, Turkey"
      ],
      "name": "Busra Baser Taskin"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey"
      ],
      "name": "Dilara Unal"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Istanbul Medeniyet University Faculty of Medicine, Istanbul, Turkey"
      ],
      "name": "Lutfiye Koru"
    },
    {
      "affiliations": [
        "Department of Pediatric Immunology and Rheumatology, Uludag University Faculty of Medicine, Bursa, Turkey"
      ],
      "name": "Hatice Kubra Zora"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey"
      ],
      "name": "Aslihan Uzun Bektas"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Gaziantep University Faculty of Medicine, Gaziantep, Gaziantep, Turkey"
      ],
      "name": "Melisa Kacmaz"
    },
    {
      "affiliations": [
        "Department of Paediatric Rheumatology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey"
      ],
      "name": "Halil Kazanasmaz"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Marmara University Faculty of Medicine, Istanbul, Turkey"
      ],
      "name": "Sengul Caglayan"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Adana City Training and Research Hospital, Adana, Turkey"
      ],
      "name": "Seher Sener"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Gazi University Faculty of Medicine, Ankara, Turkey"
      ],
      "name": "Busra Acun"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Mardin Training and Research Hospital, Mardin, Turkey"
      ],
      "name": "Gulcan Ozomay Baykal"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Gazi Yasargil Training and Research Hospital, Diyarbakir, Turkey"
      ],
      "name": "Yasemin Yigit Demir"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Firat University Faculty of Medicine, Elazig, Turkey"
      ],
      "name": "Suleyman Ekrem Albayrak"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Samsun Training and Research Hospital, Samsun, Turkey"
      ],
      "name": "Burcu Bozkaya"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey"
      ],
      "name": "Orhan Nurlu"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Istanbul Medeniyet University Faculty of Medicine, Istanbul, Turkey"
      ],
      "name": "Fatih Haslak"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Istanbul, Turkey"
      ],
      "name": "Mehmet Yildiz"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Istanbul, Turkey"
      ],
      "name": "Amra Adrovic"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Istanbul, Turkey"
      ],
      "name": "Kenan Barut"
    },
    {
      "affiliations": [
        "Department of Medical Genetics, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey"
      ],
      "name": "Halil İbrahim Yılmaz"
    },
    {
      "affiliations": [
        "Department of Medical Genetics, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey"
      ],
      "name": "Mustafa Dogan"
    },
    {
      "affiliations": [
        "Department of Medical Genetics, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey"
      ],
      "name": "Alper Gezdirici"
    },
    {
      "affiliations": [
        "Department of Medical Genetics, Umraniye Education and Research Hospital, University of Health Sciences, Istanbul, Turkey"
      ],
      "name": "Metin Eser"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Erciyes University Faculty of Medicine, Kayseri, Turkey"
      ],
      "name": "Sumeyra Ozdemir Cicek"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Cukurova University Faculty of Medicine, Adana, Turkey"
      ],
      "name": "Sibel Balci"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Firat University Faculty of Medicine, Elazig, Turkey"
      ],
      "name": "Metin Kaya Gurgoze"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey"
      ],
      "name": "Ayse Balat"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Gazi University Faculty of Medicine, Ankara, Turkey"
      ],
      "name": "Sevcan A Bakkaloglu"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey"
      ],
      "name": "Balahan Bora"
    },
    {
      "affiliations": [
        "Department of Pediatric Immunology and Rheumatology, Uludag University Faculty of Medicine, Bursa, Turkey"
      ],
      "name": "Sara Sebnem Kılıc"
    },
    {
      "affiliations": [
        "Department of Paediatric Rheumatology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey"
      ],
      "name": "Mukaddes Kalyoncu"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, University of Health Sciences, Etlik City Hospital, Ankara, Turkey"
      ],
      "name": "Semanur Ozdel"
    },
    {
      "affiliations": [
        "Department of Medical Genetics, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey"
      ],
      "name": "Oya Koker"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Istanbul University Faculty of Medicine, Istanbul, Turkey"
      ],
      "name": "Nuray Aktay Ayaz"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey"
      ],
      "name": "Seza Ozen"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara, Turkey"
      ],
      "name": "Banu Celikel Acar"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Erciyes University Faculty of Medicine, Kayseri, Turkey"
      ],
      "name": "Aysenur Pac Kısaarslan"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Cukurova University Faculty of Medicine, Adana, Turkey"
      ],
      "name": "Rabia Miray Kısla Ekinci"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, Istanbul, Turkey"
      ],
      "name": "Betul Sozeri"
    },
    {
      "affiliations": [
        "Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Istanbul, Turkey"
      ],
      "name": "Ozgur Kasapcopur"
    }
  ],
  "title": "LBA:01:27 Monogenic lupus: genetic results, clinical spectrum, and outcomes from a nationwide multicenter cohort",
  "uid": "a65aca5b-7ed5-593a-bda6-72243a5ef49b"
}