{
  "abstract": "Objectives DNASE1L3 deficiency is a rare monogenic cause of early-onset SLE and HUV, but long-term adult outcome data are limited. We report longitudinal disease trajectory, damage accrual, and mortality in the largest DNASE1L3 cohort to date.Methods We performed a multicenter longitudinal cohort study including patients with genetically confirmed DNASE1L3 deficiency from Oman and the UAE. Clinical, laboratory, and treatment data were collected from initial pediatric diagnosis through last adult follow-up. Disease activity and irreversible damage were assessed using SLEDAI and the SLICC/ACR Damage Index. Longitudinal comparisons were made between the last pediatric assessment and adult follow-up. Outcomes included organ involvement, flare rates, hospitalizations, serious infections, cumulative damage, and mortality.Results Forty patients with confirmed DNASE1L3 deficiency were included. Median age at diagnosis was 4 years, with a mean disease duration of 11.5 years. At presentation, 52.5% fulfilled ACR/EULAR criteria for SLE, while 47.5% fulfilled Schwartz criteria for HUVS without SLE classification; however, by last adult follow-up, all patients fulfilled ACR/EULAR criteria for SLE.Clinical, laboratory, treatment and outcome findings across the two stages are shown in tables 1–4. Mean SLEDAI scores decreased from 13.8 to 9.7 (p=0.002), yet this was not paralleled by improved outcomes as the Mean SLICC/ACR Damage Index increased from 0.35 (range 0–3) to 0.48 (range 0–3).Chronic organ damage increased from 19% to 31% (p=0.370). Renal involvement remained the dominant manifestation, with rising rates of lupus nephritis (32% to 50% p=0.161), predominantly classes (III/IV). Pulmonary involvement, absent at baseline, emerged in 14% of patients during follow-up (p=0.054). Skeletal morbidity was frequent, with osteoporosis increasing from 31% to 41% (p=0.401).Annual flare rates remained low (0.51 vs. 0.77 flares/year, p=0.844), as did hospitalization (0.67 vs. 0.68, p=1.000). Serious infectious events were uncommon and decreased over time (0.39 vs. 0.21 events/year, p=0.343).Mortality increased following transition to adult care, from 10% to 17.4% (p=0.448) with catastrophic events observed in 13% of adult patients (p=0.059).Abstract LBA:01:30 Table 1Conclusions Despite reduced disease activity, patients with DNASE1L3 deficiency experience progressive organ damage and mortality in adulthood, indicating that low clinical activity may mask ongoing subclinical progression and underscoring the need for vigilant long-term care.",
  "authors": [
    {
      "affiliations": [
        "Sultan Qaboos University, Muscat, Oman"
      ],
      "name": "Reem Abdwani"
    },
    {
      "affiliations": [
        "Royal Hospital, Muscat, Oman"
      ],
      "name": "Safiya Al Abrawi"
    },
    {
      "affiliations": [
        "United Arab Emirates University, Al Ain, United Arab Emirates"
      ],
      "name": "Najla Al Jabri"
    },
    {
      "affiliations": [
        "Oman Medical Speciality Board, Muscat, Oman"
      ],
      "name": "Kawthar Al Shukaili"
    },
    {
      "affiliations": [
        "Oman Medical Specialty Board, Muscat, Oman"
      ],
      "name": "Shama Al Shimli"
    },
    {
      "affiliations": [
        "University Medical City, Muscat, Oman"
      ],
      "name": "Mahadev Mal"
    },
    {
      "affiliations": [
        "Royal Hospital, Muscat, Oman"
      ],
      "name": "Ruqaiya Al Jashmi"
    },
    {
      "affiliations": [
        "University Medical City, Muscat, Oman"
      ],
      "name": "Eman Al Masroori"
    },
    {
      "affiliations": [
        "Sultan Qaboos University, Muscat, Oman"
      ],
      "name": "Ibrahim Zakwani"
    },
    {
      "affiliations": [
        "University of Southern California, Los Angeles, USA"
      ],
      "name": "Andreas Reiff"
    }
  ],
  "title": "LBA:01:30 Long-term clinical outcomes in DNASE1L3 deficiency: reduced disease activity does not prevent progressive organ damage",
  "uid": "2187de9f-d2ca-567d-a632-82f7c42e2405"
}