CD23 and Its Genetic Polymorphisms
in Allergic Reactions
Jianfeng Meng, MD, MPH
Department of Pediatric Immunology Research
Children’s Mercy Hospital
University of Missouri at Kansas City
School of Medicine
Mentor: Jonathan Arm, MD
CD23
Kijimoto-Ochiai S., 2002
1. IgE Binding Domain
2. Cytoplasmic Domain
3. Leucine Zipper Domain
4. Protease Cleavage Sites
5. Reverse RGD Domain
6. RGD Binding Inhibition
Peptide
1
2
6
5
4
3
Dose Dependent Decrease in Total IgE with
the Anti-CD23 Monoclonal Antibody
(Lumiliximab)
Single Dose Given
Placebo
0.05 mg/kg
0.25 mg/kg
1.0 mg/kg
4 & 10 mg/kg
15 mg/kg
Mean Percent Change in Serum IgEStudy Days
Rosenwasser, JACI 2003;112:563-70.
Key Roles of CD23 in Allergic Reactions
• Antigen presentation via IgE antigen
complex
• Activation and Differentiation of Antigen
Presentation Cells ( B Cells, Monocytes
etc.)
• Regulation of IgE Synthesis
• Production and release of proinflammatory
mediators ( IL1b, TNFa, IL8, NO, etc)
IL4
IL13
IL5
GM-CSF
APCs
CD3
TCR
CD4
CD40
CD154
CD86
CD80
CD28
IgE
IL1, TNF-alpha ,etc
IL2
T cells
MHC II
CD23(FcεRII)
IgE-antigen
complex
IL10, TGFβ
sCD23
MHCII
CD11b, /CD11c etc
IL-12
IFN-r etc.
sCD23
CD21
CD23
Association of CD23 Haplotype with
Asthma Severity: GCTTA
0
5
10
15
20
25
30
35
40
45
50
% with HaplotypeHospitalizations
ER Visits
p = 0.0001 (Hosp) and 0.01 (ER)
Yes
No
CAMP Data
3733 Nci I |3750 3762
agagggctgcccggaacggtatga
tctcccgacgggccttgccatact
Arg
3733 |3750 3762
agagggctgcctggaacggtatga
tctcccgacggaccttgccatact
Trp
Genotypes of SNP R62W (NC_000019)
TT
CC
CT
393bp
183bp
210bp
Kijimoto-Ochiai S., 2002
R W
No Association between SNP
R62W and Allergy Status
Groups
Allergy
Non allergy
P value
N
22
20
Age
38.0 ± 11.12
37.18 ± 8.96
>0.05
Gender
Male
10 (0.45)
11 (0.55)
Female
12 (0.55)
9 (0.45)
>0.05
Ethnicity
White
11 (0.5)
12 (0.6)
Asian
5 (0.23)
8 (0.4)
>0.05
Hispanic
2 (0.09)
0
Black
1 (0.04)
0
Others
3 (0.14)
0
Genotype for CD23 R62W
Hetero (TC)
5 (0.23)
6 (0.3)
Homo (TT)
1 (0.04)
1 (0.05)
Wild (CC