APDS patients with immune-complex vasculitis and resolution with leniolisib

Mohammad-Ali Doroudchi; Alexis V Stephens; Ziwei Wang; Jaspreet Dhami; Manish J Butte

doi:10.1016/j.clim.2024.110176

APDS patients with immune-complex vasculitis and resolution with leniolisib

Clin Immunol. 2024 May:262:110176. doi: 10.1016/j.clim.2024.110176. Epub 2024 Mar 8.

Authors

Mohammad-Ali Doroudchi¹, Alexis V Stephens¹, Ziwei Wang², Jaspreet Dhami³, Manish J Butte⁴

Affiliations

¹ Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, USA.
² Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
³ UCLA Health / VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
⁴ Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, USA; Department of Microbiology Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, USA; Department of Human Genetics, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: mbutte@mednet.ucla.edu.

PMID: 38462154
DOI: 10.1016/j.clim.2024.110176

Abstract

Activated phosphoinositide 3-kinase delta syndrome (APDS) is an inborn error of immunity with heterogeneous clinical manifestations of infections, immune dysregulation, autoimmunity; lymphoproliferation; and malignancy. Immune complex-mediated vasculitides have not yet been described in APDS patients. Here we offer a case series of three patients with APDS who have refractory IgA vasculitis (also called Henoch-Schönlein purpura), a form of immune complex-mediated vasculitis that activates complement and attracts neutrophils, macrophages and eosinophils to cause local tissue injury. Leniolisib is an inhibitor of PI3K p110δ and an FDA-approved treatment for APDS. IgA vasculitis resolved upon treatment with leniolisib. Patients with immune dysregulation including IgA vasculitis should be screened for APDS.

Keywords: Activated PI3K Delta syndrome; IgA vasculitis; Immune complex; Leniolisib; vasculitis.

MeSH terms

Antigen-Antibody Complex
Giant Cell Arteritis*
Granulomatosis with Polyangiitis*
Humans
IgA Vasculitis*
Mucocutaneous Lymph Node Syndrome*
Phosphatidylinositol 3-Kinase / therapeutic use
Phosphatidylinositol 3-Kinases
Polyarteritis Nodosa*
Pyridines*
Pyrimidines*

Substances

Antigen-Antibody Complex
Phosphatidylinositol 3-Kinase
leniolisib
Phosphatidylinositol 3-Kinases
Pyridines
Pyrimidines