2. Group of primary immunodeficiencies
Significant elevation of IgE
Recurrent skin infections
Eczema
Pulmonary infection
Cur Opin Hematol 2015, 22:12-22
6. First described as "Job's syndrome" in 1966
Bablical Job : smote with sore boil
In 1972, extremely high serum IgE level
In 2008, known about mutation of STAT3
Immunol Allergy Clin N Am 28(2008) 227-291
7. Dominant-negative heterogenous mutation in
STAT3
STAT3 located at 17q21.31
Mutation mostly in SH2 and DNA binding
domains of STAT3 and mostly missense
mutations --> single amino acid changes or
short in-frame deletion
Immunol Allergy Clin N Am 35 (2015) 767-778
Artritis research and therapy 2012 14:228
12. Newborn rash usually first manifestation
First month of life : Pustular and eczematoid
rash esp. at face and scalp
Histology : eosinophilic infiltration
Culture : Staphylococcus aureus
Boils : cold abcess
Immunol Allergy Clin N Am 28(2008) 227-291
13. Recurrent pyogenic pneumonia
Organisms : S aureus, Streptococcus
pneumoniae and Haemophilus influenzae
Complication : pneumatoceles, bronchiectasis
Structural abnormalities --> gram negative
bacterial infection ex. Pseudomonas and fungal
infection
Immunol Allergy Clin N Am 28(2008) 227-291
14.
15. Not much
Do not have Th2 predominance
Most IgE is not allergen-specific
Impaired IL-10 induced generation of tolerogenic
dendritric cells --> reduced generation of induced
regulatory T cell SO patient may manifest
anaphylaxis and have more allergy compared to
healthy
Cur Opin Hematol 2015, 22:12-22
18. Scoliosis : vary in severity
Osteopenia
Minimal trauma fractures
Hyperextensibility : large and small joint
Degenerative joint disease
Immunol Allergy Clin N Am 28(2008) 227-291
20. Failure of the primary dental teeth to exforiate
Immunol Allergy Clin N Am 28(2008) 227-291 Oral disease 2008
21. Peripheral and brain artery abnormalities
Coronary artery abnormalities : ectasias and
aneurysm
In mouse model, inhibited STAT3 signaling
and IL-17A blockage resulted in increased
aneurysm severity and fatal ruptures
Cur Opin Hematol 2015, 22:12-22
25. Gold standard : molecular diagnosis with
sequencing of STAT3
Often leucocytosis, rare neutopenia
Normal IgG
Immunol Allergy Clin N Am 35 (2015) 767-778
27. Firstly described in 2004 by Renner et al.
Consanguineous families
Feature of HIES but lack of connective tissue
disease and skeletal affect
Increased in viral infections
More neurologic symptoms, autoimmunity,
food allergy and higher rate of malignancies
Cur Opin Hematol 2015, 22:12-22
28. DOCK8 : guanine nucleotide exchange factor
Interacts with Rho GTPases
Regulatory function in cell migration,
morphology, adhesion and growth
Cur Opin Hematol 2015, 22:12-22
29. Mutation in DOCK8 : 9p24.3
Premature termination
Frameshift
Splice site disruption
Single exon deletions
Microdeletion
Cur Opin Hematol 2015, 22:12-22
30. Mutation in DOCK8 : 9p24.3
Premature termination
Frameshift
Splice site disruption
Single exon deletions
Microdeletion
Cur Opin Hematol 2015, 22:12-22
Loss of function
31. Severe reduction of memory B cells
Some impaired antibody responses to
immunization and long term memory
T cell number below average and some
diminishes proliferation
Cur Opin Hematol 2015, 22:12-22
32. Impaired NK cell function
Decreased plasmacytoid dendritic cell
numbers
Decreased expression of TNF-alpha, IFN-
gamma and IL-2
Cur Opin Hematol 2015, 22:12-22
33. Elevated serum IgE level with
CD3+, CD4+, naive CD8+ T cell
Lymphopenia
Normal total B lymphocyte percentage but
low memory B lymphocyte value
43. Gold standard : molecular sequencing of
DOCK8 gene
Usually low T cell in number, low IgM level
and failure to sustain protective titer against
vaccination
Immunol Allergy Clin N Am 35 (2015) 767-778
45. First reported in 2006
Multiple episodes of staphylococcus disease,
severe eczema and elevated IgE level
Additionally, suffered from susceptibility to
BCG and Salmonella : IFN-gamma/IL-12
defect
Cur Opin Hematol 2015, 22:12-22
51. Multidisciplinary approach
Prevention and management of infection
Bone marrow transplantation may be curative
Immunol Allergy Clin N Am 35 (2015) 767-778
Ann N.Y. Acad. Sci. 1246(2011) 26-33