An old research project conducted at Queen Mary's Childrens Hospital (St Helier's Hospital) thanks to Nuffield. This is a summary of my research into mannose-binding lectin.

1. Katherine Burke

2. Who I Am

3. The aim of the study is to give a brief introduction into:
• What I mean by mannose-binding lectin (MBL)
• The clinical features of deficiency
• How to test for MBL
• The significance of MBL (if any)
Aim

4. Background
 MBL was first found in baker’s yeast as a
plasma
 In 1968 there was a case report of a child with
recurrent infections due to a deficiency –
although MBL was unknown at the time
 1987 saw that MBL was recognised to
activate complement
 Since then research has been increasing on
the subject and yet still much is unknown

5. What MBL is
 MBL is a plasma
glycoprotein in the collectin
family
 MBL is part of the innate
immune system
 It is commonly known now
to activate the complement
system through the lectin
pathway
 In humans, MBL normal
forms 1-6 subunit oligomers
 The more subunits the
stronger the bonding to the
microbe
C-Terminal

6. Mutations
Mutation Codon Base Change Amino Acid
Change
B 54 GGC  GAC Gly  Asp
C 57 GGA  GAA Gly  Glu
D 52 CGT TGT Arg  Cys
Two of the mutations occur in the collagen-like
domain (B and C)
The third (D) mutation prevents dioligomers to form
thus creating poorly functional MBL
(A) would represent the wild type (or ‘normal’)

7. Clinical Features
 The main clinical feature would be to have
recurrent infections
 The research done on MBL has also concentrated
on recurrent respiratory infections in particular
 The clinical features were collected by doing a
case study of 7 patients that were deficient and
then comparing some categories to controls with
high MBL
 As MBL deficiency is genetically based, it was
important to find out any family history

8. Clinical Features

9. Family History

10. Investigations

11. MBL ELISA
 ELISA (enzyme-linked immunosorbent
assay) is the method used to test for
MBL deficiency
 The principle is that MBL if present will
bind to antibodies, then antibodies with
enzymes will attach onto this
 Substrates will bind it enzymes and
then this is produce a colour intensity,
which can be measured to see if there is
any MBL present
 The results are compared to a standard
curve and high and low controls
 The idea is that the amount of substrate
is directly proportional to the amount of
MBL in the given sample
1hr
1hr
1hr
15m
Wash x3
Wash x3
Wash x3

12.  If the results are more than 1300 ng/mL, the patient has normal alleles with no risk of recurrent infections
 If the value is between 400-1300 ng/mL, the patient has a mild deficiency with some risk of recurrent
infections
 It also shows that the patient is heterozygous for MBL
 However, if the patient has a value between 75-399.99 ng/mL, then the patient has a functional
deficiency of MBL with an increased risk of recurrent infection
 If the value is less than 75 ng/mL, the patient is mutant homozygous without functional MBL
 These patients would have the greatest risk of recurrent infections

13.  If the results are more than 1300 ng/mL, the patient has normal alleles with no risk of recurrent infections
 If the value is between 400-1300 ng/mL, the patient has a mild deficiency with some risk of recurrent
infections
 It also shows that the patient is heterozygous for MBL
 However, if the patient has a value between 75-399.99 ng/mL, then the patient has a functional
deficiency of MBL with an increased risk of recurrent infection
 If the value is less than 75 ng/mL, the patient is mutant homozygous without functional MBL
 These patients would have the greatest risk of recurrent infections

14. Treatment
 Generally, the treatment for an MBL deficiency is
difficult is assess
 Most of the individuals were mostly healthy
 The MBL deficiency only detected when the
immune system is compromised already
 Treatment mainly consisted of antibiotics (in
winter) and for the other problems

15. Conclusions (1)
 In conclusion, MBL deficiency is
genetically based
 The main features of this would be that a
patient would have recurrent infections
 To test for this one would use the
technique ELISA
 This would show to what extent a patient
was deficient if at all although it would not
show the alleles that were mutant or the
wild type

16. Conclusions (2)
 There has been research to show there is an
advantage of having a MBL deficiency but
more research needs to be done into this
 Generally, an MBL deficiency would lead to
an increased risk of recurrent infections and
therefore is treated with antibiotics
 However, there is a possibility that a
replacement therapy may be available soon
 Clinically, it is significant to explain why a
patient has recurrent infections and to treat
it accordingly

17. I’d like to thank a few people that made this project possible
and helped me along the way:
• Dr. Sonny Chong who thought of the project
• Dr. Grant Hayman who also helped think of the project
• Alex Nichols who was kind enough to do the lab work with me
• Dr. Hany Banoub
• Imran Bhatia
• The kind staff in the immunology lab
• The lovely secretaries in paediatrics without whom I would
have been lost on countless occasions
• Denise Balmer who organised the Nuffield Bursary placement
• Dr. Sheikh who introduced me to the scheme
Acknowledgements