- Patient presentation
- Differential Diagnosis
- Final outcome
- Evaluation - Questions & answers
An 8 year old boy is referred to a regional hospital for a surgical consultation for a lobectomy following a diagnosis of bronchiectasis due to a chronic history of recurrent respiratory infections.
This case study was kindly provided by Dr Monika Esser MMed Paed, Head of Division of Immunology, N.H.L.S Coastal Branch, Tygerberg Hospital.
- Bacterial meningitis at age 2 years complicated by deafness – for which he currently attends a school for hearing impaired children.
- Pulmonary TB fully treated, exact age at time of treatment unknown.
- Currently presents with bronchiectasis due to recurrent respiratory infections.
- No significant family history.
- X- linked Agammaglobulinaemia (Bruton’s Disease)
- Hyper IgM Syndrome
- Common variable immunodeficiency
- Severe Combined Immunodeficiency
On general examination:
- Does not appear acutely ill
- Weight on 75th centile, height 90th centile
- Clubbing of fingernails
- Persistent productive cough
- Harrison’s sulcus
- Bilateral lower lobe crepitations
- Nil of note
|WBC||11.11 x 10’9/L – 81.3% Lymphocytes|
|Platelets||397 x 10’9/L|
|(no other counts available)|
|H. Influenza and||Isolated on culture|
|CXR||Suggestive of bronchiectasis with superimposed infection|
|IgE||4.3 IU/ml||(>60 IU/ml)|
|Lymphocyte Subset Analysis:|
|CD19 1% (L)||90 (L)|
|CD3 97% (H)||8759 (H)|
|CD4 22% (L)||1987 (H)|
|CD8 68% (H)||6140 (H)|
|NK 8% (L)||722 (H)|
|Lymphocyte subsets showed low but not entirely absent CD19 (B cells) and elevated C3 and NK cells.|
The Role of CD40 and its ligand (CD154)
CD40, member of the TNF receptor family, is expressed by a variety of cells including B cells, macrophages, dendritic cells and other nonimmune cell types.
CD40 activation occurs via binding to its ligand CD154, which is expressed on activated T cells.
CD40 activation is critical for:
Mutations in either CD40 or CD154 gene cause Hyper IgM Syndrome, HIGM3 and HIGM1 respectively, which is characterised by:
- Normal or elevated SeIgM
- Markedly decreased IgG, IgA, IgE
Due to lack of CD154, T cell interaction with protein antigen processing cells such as CD19 is impaired preventing ligand interaction of B cell CD40 with CD154 on T cells with subsequent defective response to T cell dependent antigens i.e. the immunological synapse is not formed. This synapse gives essential co-stimulatory signal to B cells necessary for the B cells to switch from low affinity IgM production primary response to the B cell producing high affinity antibodies of different classes such as IgG and IgA.
- Physiotherapy daily. After 4 weeks of intensive physio a CT chest confirmed bilateral basal bronchiectasis.
- Broad spectrum antibiotics were initiated.
- IVIG at 0,4g/kg – 3 weekly infusions. (Antibody studies to common vaccine antigens were not done prior to IVIG therapy and are therefore not available).
- IVIG infusions 3 weekly to maintain normal serum levels of IgG and prompt treatment with antibiotics for bacterial infections.
- Prevention or early recognition of protozoal infections of liver and GIT.
- Cotrimoxazole prophylaxis for PCP infections.
- Bone marrow transplant would have been the curative treatment of choice, prior to established bronchiectasis.
Evaluation – Questions & answers
What is the diagnosis?
Give possible reasons for bronchiectasis developing in childhood.
What else on history is essential for evaluating this patient with regards to immunity?
Which other clinical findings would you like information on?
If this child has a primary or secondary Immunodeficiency - which component of the immune response do you expect to be impaired?
Comment on the immunoglobulin levels and lymphocyte phenotypes.
How do you explain a normal Se IgM with the other Immunoglobulin isotypes low?
Could this patient have X-linked Agammaglobulinaemia (XLA) (Bruton’s)?
What is the possible cause of the T cell subset abnormal distribution?
How would you expect a patient with very low B cells to respond to vaccination?
Who in the boy’s family would possibly be the best match for HLA typing for a bone marrow transplant?