Saliha Esenboğa, Turkey
Hacettepe University Faculty of Medicine Pediatric ImmunologyPresenter of 2 Presentations
A CVID PATIENT WITH PIK3R1 DEFECT
Abstract
Background and Aims
PI3Kδ is a heterodimeric complex containing a p110δ catalytic molecule and a p85a regulatory subunit encoded by the PIK3CD and PIK3R1 genes, which play a critical role in the regulation of immune responses.The heterozygous gain of function mutations of p110δ, and exon-skipping mutations of p85a cause hyperactivation of the PI3Kδ complex and cause APDS type 1 (APDS1) and APDS2. Patients present in the childhood with recurrent bacterial and viral sinopulmonary infections which often complicate with bronchiectasis. Autoimmune cytopenia and gastrointestinal findings are also frequently observed. There is increased risk of lymphoproliferative diseases, and lymphoma.
Here, we present a case with PIK3R1 defect diagnosed with CVID.
Methods
At 5 years of age, the patient was admitted to the hospital due to recurrent lung infections, pleural effusion, and the history of zona zoster infection. Intravenous immunoglobulin(IVIG)treatment was started with the diagnosis of CVID at 7 years of age because of hypogammaglobulinemia and absence of specific antibody response, . In addition to low immunoglobulin levels, B cell (CD19+) percentage and counts progressively decreased during follow-up. Thorax CT revealed millimetric nodular opacities in both lungs and mucus plugs.
Results
At the age of 20, the molecular analysis revealed mutation in PIK3R1 gene (c.712C> T, p. Leu238Phe).
Conclusions
APDS should be kept in mind in patients presenting with recurrent lung infections and inflammatory diseases.Molecular diagnosis provides clinicians to use mTOR or PI3Kδ inhibitors in the management of patients as a bridge therapy until HSCT is performed.
AUTOSOMAL RECESSIVE AGAMMAGLOBULINEMIA AND A RARE GENETIC DEFECT: CD79A
Abstract
Background and Aims
Any disorder that develops during the development or differentiation of B cells may cause hypo / agamaglobulinemia by affecting immunoglobulin production from plasma cells.
Methods
The clinical , laboratory characteristics of patients, mutations detected inCD79A gene are shown in Table 1.
Results
Patient1 A 12-month-old girl was admitted with recurrent bronchiolitis and neutropenia. She had been suffering from recurrent diarrhea since 15 days old. There was no consanguinity between parents(coming from same village) She was found to have agammaglobulinemia, CD 19 <1%. IVIg treatment has begun.
Patient2 A 13-month-old male patient presented with progressive muscle-weakness without focal neurological deficit. He had been suffering from recurrent pneumonia and otitis media from 8 months of age and the laboratory evaluation revealed agammaglobulinemia, CD19 <0.1%. VIg therapy was initiated. Muscle weakness improved in thefirst 3 months after IVIg. Dermatomyositis-like skin findings were detected at 2 yearsofage. He died attheage of 8 due to pneumonia. Since there was no relationship between the parents, BTK mutation was found to be negative.
Patient3 A 15-month-old girl applied with the complaints of URTI, pneumonia and diarrhea. She had URTI at 3 months ofage for the first time and had recurrent pneumonia and needed iv.antibiotic treatment and hospitalisations in thefollowing period. There was consanguinity. Immunologicalevaluation revealed agamaglobulinemia, CD19 0%.IVIg replacement therapy was started.
Conclusions
Igα-deficiency leads a block in the transition from pro-B cell to pre-B cell during B cell differentiation. Enteroviral infections, growth retardation, neutropenia, recurrent bronchitis, otitis, diarrhea, and vaccine-related polio may occur during the course of the disease.