Recurrent Infection in a

3-year-old girl
Zeb, Mary, Manuella, Ashley, and Leia

Symptoms
Patient was presenting with:
Sepsis
History of serious infections
49 days old
meningococcal meningitis and bronchitis
6 months old
meningitis and broncopneumonia
14 months old
pneumonia
19 months old
acute otitis media

Symptoms (contd.)
History of serious infections continued
26 months old
pneumonia impetigo
31 months old
Urinary tract infection
35 months old
pneumonia and tonsillitis
Slowed development
Epilepsy

Family History Information

Brother:
12 years old
recurrent otitis and tonsillitis
Sister:
8 years old
recurrent pharyngitis
Parents (first cousins): Healthy individuals

Blood Analysis
V
a
l
e
r
i
e

s
L
e
v
e
l
s

No
rm
al
Le
vel
s

Factor I Deficiency
Figure 2.9 The
Immune System, 4th
ed. (Garland Science
2015)

Chemotaxis and Phagocytic

Assays

http://en.academic.ru/pictures/enwiki/67/Chtx-asayagar.PNG

http://www.frontiersin.org/files/
Articles/20717/fmicb-0300108-r2/image_m/fmicb-0300108-g001.jpg

Chemotaxis and Phagocytic

Assays

Complement Profile

Alternative Complement
Pathway Mechanism?
C3 Hydrolyzes into C3a and C3b
C3b cleaves C5 into C5a and C5b
o Then C5b-C9 form the membrane
attack complex
The cell then lyses due to osmotic
pressure

http://en.wikipedia.org/wiki/Alternative_comple
ment_pathway

Why is there not

compartmentalized
Inflammation?

Opsonizing Signals
Opsonization-The coating of a pathogen with a protein that facilitates
phagocytosis.
https://vimeo.com/70326148

How do you get it?

Inherited by parents who are usually heterozygous
Defect on the long arm of chromosome 4
Partial Factor I Deficiency can manifest when an individual is heterozygous
displaying some but not all of the factor I symptoms

Why?
Why did valerie have epilepsy and slow development?

Why did Valerie Have so

many Infections?
Individuals with Factor I Deficiency have an increased risk of infections from
encapsulated bacteria due to the mechanism for penetration into the capsuled
bacteria to be introduced to the pathogen.
Valeri
o Haemophilus Influenzae (6 & 19 months)
o Meningitis (49 days old & 6 months old)
o Streptococcus
aureus (26 months)
pneumoniae (14, 26, and 35 months)

All
encapsulated
Bacteria!

Encapsulated Bacteria

http://upload.wikimedia.org/wikipedia/commons/thumb/5/5a/Average_prokaryot
e_cell-_en.svg/1258px-Average_prokaryote_cell-_en.svg.png

Normal VS Dysfunctional
Normal Complement
MCP(Membrane Cofactor
protein)
*Complement control
protein
-Prevent complement
fixation on human cell
surface.
1. Binds to C3b making
it inactive

Normal complement...cont.
- Factor H (Plasma complement control protein)
2. Binds to C3b and continues it to its cleavage form iC3b with the help of
-Factor I (Plasma serine protease)
3. Fragment iC3b is unable to produce a C3 convertase , Factor H and Factor I
work together to decrease the number of C3 convertase on the cell.

Dysfunctional factor I
1. MCP binds to C3b making it inactive
2. Factor I is absent so C3b cannot be made into iC3b form
3. The alternative pathway is furthered
~C5-C9
~Factor B
~Factor D
~C3
4. C3a,C3b
5. membrane attack complex (MAC)

Question 1
How did factor I deficiency lead to low chemotaxis results?
Chemotaxis is the movement of the organisms in response to chemical
stimulus to fight infections in the body
http://www.cellsalive.com/chemotx.htm

CFI gene provides instructions to complement factor I, which regulates part

of the immune system
Complement system proteins work together to destroy foreign invaders,
trigger inflammation, and remove destroyed parts from cells and tissues

Question 2
What would happen if Valerie was given a large dose of intravenous factor I?
Fresh Frozen Plasma (FFP) FFP can cause adverse reactions due to the high volumes of plasma
needed to elevate the Factor I levels resulting in an overload of the
circulatory system and stress on the heart.
Factor I Concentrate Factor I concentrates are a much safer alternative. While they are also
administered intravenously, they are given in lower dosages which do not
stress the heart. Additionally, they are manufactured and carry a lower risk
of accidental infection.

Clinical Implications
Factor I Concentrate = Higher Cost for better effective treatment
Fresh Frozen Plasma = Lower Cost for more complications
This disease is so uncommon that a significant amount money will never
be put into research to lower cost of treatments.

Question 3
Patients with factor I deficiency generally
experience fewer and fewer infections as
they age. Why?
The availability of vaccinations
Mere exposure; acquired immunity
Recommendation of fresh frozen plasma
transfusion - average ages 16-30 years old

Question 4
It is common for red blood cells of individuals with
factor I deficiency to agglutinate when exposed to
anti-C3 immunoglobulins, why?

RBC coated in C3 being activated

RBC pick up proteins
With the anti-C3, proteins are remaining on the surface
Binds to C3 and agglutinates
Indicator that the C3 pathway is not working correctly

References

http://ghr.nlm.nih.gov/condition/complement-factor-i-deficiency
http://www.mercynorthiowa.com/cbc-normal-ranges
http://www.nlm.nih.gov/medlineplus/ency/article/003456.htm
http://ghr.nlm.nih.gov/condition/complement-factor-i-deficiency

http://labtestsonline.org/understanding/analytes/complement-levels/tab/test/

http://www.ncbi.nlm.nih.gov/pubmed/10900163
https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders
/Other-Factor-Deficiencies/Factor-I
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168207/
http://faculty.madisoncollege.edu/mljensen/BloodBank/lectures/antiglobulin
_testing.htm
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2937290/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809586/
http://www.hemophilia.ca/en/bleeding-disorders/other-factor-deficiencies/fact

Cont. references

http://www.ncbi.nlm.nih.gov/books/NBK27100/
https://books.google.com/books?id=Ph7ABAAAQBAJ&pg=PA34&lpg=PA34&
dq=IC3B+cannot+produce+c3+convertase&source=bl&ots=VApHOoJ040&si
g=t44Ayl5TkV1moQiMlaEh7J3SLKQ&hl=en&sa=X&ei=a87bVLbRL5SayQSl84HA
Dw&ved=0CB4Q6AEwAA#v=onepage&q=IC3B%20cannot%20produce%20c3%20co
nvertase&f=false