Immunodeficiency and autoimmunity; Long-term follow-up of a patient with PIK3CD gene mutation associated to monogenic lupus: case report

PIK3CD syndrome results from gain of function (GOF) in the genes encoding PI3K, known as APDS1. It usually affects males (4:3) and presents with recurrent respiratory infections by S. Pneumoniae and H. Influenzae, bronchiectasis, susceptibility to severe EBV and CMV infections.
We report a 2 year-old male who presented failure to thrive, hepatosplenomegaly, recurrent respiratory infections, lymphadenopathies, anemia and bilateral bronchiectasis, pulmonary and hepatic infection by EBV. He presented autoimmunity at 9 years, with pancytopenia (lymphopenia CD4 and CD19), ANA+, hypergammaglobulinemia, and positive in b2-glycoprotein. It was identified by exome sequencing a new heterozygous and deleterious mutation in exon 24 of PIK3CD (catalytic subunit P110). The patient fulfilled SLE criteria and treatment was initiated with anti-CD20 monoclonal, immunosuppressive drugs: hydroxychloroquine (2.79 mgkgdo), azathioprine (0.9 mgkgdo) and systemic steroids in addition to antibiotic prophylaxis with TMP-SX (5mgkgdo) and itraconazole (5mgkgdo). Monthly intravenous immunoglobulin (722 mgkgdo), with favorable response in the rate of hospitalizations (3 for pneumonia) and severity of infections, since starting treatment description. Seven months ago corticosteroids were suspended and the patient is currently 14 years old and stable.
SLE is not one of the main manifestations of autoimmunity in antibody immunodeficiencies such as APDS 1, it should be considered in patients with the characteristics described here. There is no consensus in the treatment for these cases. The addition of human intravenous gamma globulin to standard immunosuppressive therapy can radically change the prognosis of these patients and decreasing the rate of hospitalizations
The GOF mutation in the PI3CKD gene can give the coexistence of immunodeficiency and autoimmunity. The current treatment options for APDS 1, include conventional immunodeficiency therapies such as immunoglobulin replacement, antibiotic prophylaxis and hematopoietic stem cell transplantation but so far no standardized treatment has been defined to prevent disease progression

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Scroll to Top