a brief introduction to mannose-binding lectin (mbl) and its clinical significance
TRANSCRIPT
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
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
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
MutationsMutation Codon Base Change Amino Acid
ChangeB 54 GGC GAC Gly AspC 57 GGA GAA Gly GluD 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’)
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
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
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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
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
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
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
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
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