A mutation in PIK3CD gene causing pediatric systemic lupus erythematosus: A case report

Medicine (Baltimore). 2019 May;98(18):e15329. doi: 10.1097/MD.0000000000015329.


Rationale: Gain of function (GOF) mutations in PIK3CD gene encoding PI3K p110δ were recently associated with a novel combined immune deficiency characterized by recurrent sinopulmonary infections, CD4 lymphopenia, reduced class-switched memory B cells, lymphadenopathy, cytomegalovirus and/or epstein-Barr virus (EBV) viremia, and EBV-related lymphoma. A subset of affected patients also had elevated serum IgM.

Patient concerns: We report a patient who was diagnosed with systemic lupus erythematosus (SLE) at a young age and was recently found to carry heterozygous mutations in PIK3CD. The patient not only presented with recurrent sinopulmonary infections, CD4 lymphopenia, lymphadenopathy, EBV viremia, and elevated serum IgM, but also met classification criteria of SLE based on persistent proteinuria and hematuria, leukopenia and anemia, low level of serum complement, and positive autoantibody for antinuclear antibodies.

Diagnoses: Activated PI3Kδ syndrome.

Interventions: Oral prednisolone and hydroxychloroquine combined with mycophenolate mofetil was given to the patient. He was currently receiving intravenous immunoglobulin per month in association with hydroxychloroquine, low-dose prednisolone, and mycophenolate mofetil.

Outcomes: At present, the level of complement restored to normal, hematuria and proteinuria disappeared, and liver function returned to normal.

Lessons: SLE may be a novel phenotype of GOF mutation in PI3CKD gene (GOF PIK3CD).

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Antibodies, Antinuclear / blood
  • Asian People / genetics
  • Class I Phosphatidylinositol 3-Kinases / drug effects
  • Class I Phosphatidylinositol 3-Kinases / genetics*
  • Complement System Proteins / analysis
  • Complement System Proteins / drug effects
  • Enzyme Inhibitors / therapeutic use
  • Epstein-Barr Virus Infections / diagnosis
  • Epstein-Barr Virus Infections / etiology
  • Epstein-Barr Virus Infections / immunology
  • Gain of Function Mutation / genetics*
  • Glucocorticoids / therapeutic use
  • Herpesvirus 4, Human / immunology
  • Humans
  • Hydroxychloroquine / administration & dosage
  • Hydroxychloroquine / therapeutic use
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunologic Deficiency Syndromes / diagnosis*
  • Immunologic Deficiency Syndromes / genetics*
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / etiology
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / therapeutic use
  • Phenotype
  • Prednisolone / administration & dosage
  • Prednisolone / therapeutic use
  • Primary Immunodeficiency Diseases


  • Antibodies, Antinuclear
  • Enzyme Inhibitors
  • Glucocorticoids
  • Immunoglobulins, Intravenous
  • Hydroxychloroquine
  • Complement System Proteins
  • Prednisolone
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CD protein, human
  • Mycophenolic Acid

Supplementary concepts

  • Activated PI3K-delta Syndrome