{
  "abstract": "Background\n\nAutosomal dominant pathogenic variants in PLCG2 are associated with autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID), characterized by immunological abnormalities and multi-system inflammation. Descriptions of associated neurological manifestations and vascular anomalies are limited. We describe three patients with APLAID, vasculopathies, neuroinflammation, and cerebral vascular tortuosity. These cases highlight underrecognized and clinically important manifestations of APLAID.Case presentations\n\nAll three patients had de novo variants in PLCG2 and early systemic inflammatory and immunodeficiency findings within the spectrum of APLAID (e.g. immune laboratory abnormalities, skin and gastrointestinal inflammation, and frequent infections). Additionally, they had notable neurological and vascular findings. Patient #1 (PLCG2 c.3420T > A; p.Asp1140Glu) is a female who had focal seizures at 16 months old. Magnetic resonance imaging (MRI) revealed right parietal leptomeningeal enhancement with white matter changes. MR angiography (MRA) showed cerebrovascular tortuosity and stenoses without evidence of vasculitis. She had extensive veno-lymphatic malformation in the thorax, abnormal renal vasculature, inferior vena cava (IVC) atresia, and bilateral pulmonary vein stenosis (PVS). Patient #2 (PLCG2 c.2122G > C; p.Ala708Pro) is a male who at four years old had an episode of status epilepticus. MRI revealed a right parietal infarct with surrounding leptomeningeal enhancement and MRA demonstrated abnormal caliber of the right middle cerebral artery (MCA), arterial tortuosity, and carotid aneurysms. His course was complicated by aortic root dilation and bilateral PVS. Patient #3 (PLCG2 c.2122G > C; p.Ala708Pro) is a male who at 16 months had a right sided focal motor seizure. MRI demonstrated infarct with associated sulcal enhancement predominantly in the left cerebral hemisphere. MRA found excessive vascular tortuosity and fenestrations. He has a dilated aortic root and ventricular septal defect (VSD).Conclusion\n\nWe present three cases of APLAID complicated by significant cerebrovascular tortuosity and seizure and two with cerebral ischemia. The etiology of stroke and/or seizures in these patients is unclear, but vasculopathy leading to perfusion deficits, neuroinflammation, or thrombosis due to underlying thrombotic diathesis or abnormal vascular anatomy may have contributed. We recommend all patients with APLAID undergo monitoring for neurologic manifestations. Additionally, we highlight important vasculopathic findings such as PVS, where early recognition for directed treatment is critical.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Immunology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.",
    "Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.",
    "Pediatrics Department, Arabian Gulf University, Manama, Bahrain.",
    "Department of Neurosurgery, Cerebrovascular Surgery and Interventions Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.",
    "Division of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.",
    "Dana Farber/Boston Children's Hospital Cancer and Blood Disorders Center, Boston, MA, USA.",
    "Division of Immunology, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.",
    "Division of Rheumatology, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.",
    "Division of Neuroradiology, Department of Radiology, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.",
    "Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.",
    "Division of Nephrology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.",
    "Harvard Medical School, Boston, MA, USA.",
    "Department of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.",
    "Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.",
    "Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.",
    "The University of Texas Southwestern Medical Center, Dallas, TX, USA.",
    "Scottish Rite for Children, Dallas, TX, USA.",
    "Assiut University Faculty of Medicine, Assiut, Egypt.",
    "Division of Allergy/Immunology at Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.",
    "Translational Genetics and Genomics Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.",
    "Division of Immunology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Fatma.Dedeoglu@childrens.harvard.edu.",
    "Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Milena.Andzelm@childrens.harvard.edu."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 27,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kosar Asna Ashari"
    },
    {
      "affs": [
        1
      ],
      "name": "Rebecca MacRae"
    },
    {
      "affs": [
        0
      ],
      "name": "David P Hoytema van Konijnenburg"
    },
    {
      "affs": [
        0
      ],
      "name": "Craig D Platt"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Maryam Ashoor"
    },
    {
      "affs": [
        3
      ],
      "name": "Alfred P See"
    },
    {
      "affs": [
        1
      ],
      "name": "Agnieszka Kielian"
    },
    {
      "affs": [
        4
      ],
      "name": "Amy Danehy"
    },
    {
      "affs": [
        5
      ],
      "name": "Riten Kumar"
    },
    {
      "affs": [
        6
      ],
      "name": "Elliot James"
    },
    {
      "affs": [
        7
      ],
      "name": "Kristin Houghton"
    },
    {
      "affs": [
        8
      ],
      "name": "Sheri Harder"
    },
    {
      "affs": [
        1
      ],
      "name": "Mark P Gorman"
    },
    {
      "affs": [
        9
      ],
      "name": "Stacy A Kahn"
    },
    {
      "affs": [
        10
      ],
      "name": "Ankana Daga"
    },
    {
      "affs": [
        11
      ],
      "name": "Sadaf H Hussain"
    },
    {
      "affs": [
        12
      ],
      "name": "Alicia M Johnston"
    },
    {
      "affs": [
        13
      ],
      "name": "Alicia Casey"
    },
    {
      "affs": [
        9
      ],
      "name": "Jodie D Ouahed"
    },
    {
      "affs": [
        13
      ],
      "name": "Wai Wong"
    },
    {
      "affs": [
        14
      ],
      "name": "Kathy Jenkins"
    },
    {
      "affs": [
        5
      ],
      "name": "Susan Prockop"
    },
    {
      "affs": [
        15,
        16,
        17
      ],
      "name": "Esraa Eloseily"
    },
    {
      "affs": [
        18
      ],
      "name": "Kimberly Risma"
    },
    {
      "affs": [
        19
      ],
      "name": "Michael J Ombrello"
    },
    {
      "affs": [
        20
      ],
      "name": "Fatma Dedeoglu"
    },
    {
      "affs": [
        21
      ],
      "name": "Milena M Andzelm"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f5j8rd0mwxrcn.bib",
  "cited_by": 0,
  "doi": "10.1186/s12969-026-01227-2",
  "fulltext_url": "https://europepmc.org/articles/PMC13681867",
  "id": "f5j8rd0mwxrcn",
  "issns": [
    "1546-0096"
  ],
  "landing_url": "https://europepmc.org/article/MED/42902271",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC925-935"
    ],
    [
      "lcc",
      "RJ1-570"
    ],
    [
      "openalex",
      "2403|Immunodeficiency and Autoimmune Disorders"
    ]
  ],
  "openalex": "W7204664292",
  "pdf_url": "https://europepmc.org/articles/PMC13681867?pdf=render",
  "pmcid": "PMC13681867",
  "pmid": "42902271",
  "published": "2026-08-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/f5j8rd0mwxrcn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42902271",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42902271"
    },
    {
      "first_seen": "2026-10-30T13:45:47Z",
      "native_id": "a5b13b5c3f0e4121a9b34f89ebfa36c5",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s12969-026-01227-2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immunodeficiency and Autoimmune Disorders",
      "subfield": "immunology"
    }
  ],
  "title": "Neurological manifestations and vasculopathy in PLCG2-associated antibody deficiency and immune dysregulation (APLAID): a case series.",
  "title_text": "Neurological manifestations and vasculopathy in PLCG2-associated antibody deficiency and immune dysregulation (APLAID): a case series.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:47Z",
  "url": "https://research.draconitic.com/paper/f5j8rd0mwxrcn",
  "venue": "Pediatric rheumatology online journal",
  "versions": []
}