Evidence map›Paper›PMID 42902271›Full record

ArticlePediatric rheumatology online journal2026

Neurological manifestations and vasculopathy in PLCG2-associated antibody deficiency and immune dysregulation (APLAID): a case series.

Kosar Asna Ashari, Rebecca MacRae, David P Hoytema van Konijnenburg, Craig D Platt, Maryam Ashoor, Alfred P See, Agnieszka Kielian, Amy Danehy, Riten Kumar, Elliot James and 17 more

Abstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Pediatric rheumatology online journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

27 authors.

Kosar Asna AshariDivision of Immunology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Rebecca MacRaeDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
David P Hoytema van KonijnenburgDivision of Immunology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Craig D PlattDivision of Immunology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Maryam AshoorDivision of Immunology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Alfred P SeeDepartment of Neurosurgery, Cerebrovascular Surgery and Interventions Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Agnieszka KielianDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Amy DanehyDivision of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Riten KumarDana Farber/Boston Children's Hospital Cancer and Blood Disorders Center, Boston, MA, USA.
Elliot JamesDivision of Immunology, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.
Kristin HoughtonDivision of Rheumatology, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.
Sheri HarderDivision of Neuroradiology, Department of Radiology, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.
Mark P GormanDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Stacy A KahnDivision of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Ankana DagaDivision of Nephrology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Sadaf H HussainHarvard Medical School, Boston, MA, USA.
Alicia M JohnstonDepartment of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Alicia CaseyDivision of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Jodie D OuahedDivision of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Wai WongDivision of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Kathy JenkinsDepartment of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Susan ProckopDana Farber/Boston Children's Hospital Cancer and Blood Disorders Center, Boston, MA, USA.
Esraa EloseilyThe University of Texas Southwestern Medical Center, Dallas, TX, USA.
Kimberly RismaDivision of Allergy/Immunology at Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Michael J OmbrelloTranslational Genetics and Genomics Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Fatma DedeogluDivision of Immunology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Fatma.Dedeoglu@childrens.harvard.edu.
Milena M AndzelmDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Milena.Andzelm@childrens.harvard.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAutosomal 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: All 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).

conclusionWe 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.

Indexed as

Immunologic Deficiency SyndromesPhospholipase C gammaFemaleHumansInfantMagnetic Resonance AngiographyMagnetic Resonance ImagingMalePhospholipase C gammaPLCG2 protein, humanAPLAIDAutoinflammationCerebrovascular tortuosityNeuroinflammationPLCG2–associated antibody deficiency and immune dysregulationVasculopathy

Identifiers

PMID42902271
PMCPMC13681867

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