So very typically in an infant
with primary immunodeficiency, the
child will be getting recurrent
infections that’ll be quite severe.
Of course all children get infections
but usually one or two days later
they’re fit and well and they’re running
around again, perfectly healthy.
But in children with primary
immunodeficiencies, they will not recover
very well from these infections and
the parents maybe will be a bit
concerned and they’ll take them along
to the doctor’s clinic and eventually
they may get investigated if primary
immunodeficiency is suspected.
And there are a number of different
tests that can be carried out
to try and help in the diagnosis of primary immunodeficiency.
For example, the number of cells of
the immune system can be counted.
One can look for the
number of CD3+ lymphocytes.
CD3 is a molecule that’s found
on the surface of all T-cells, so
this will tell you whether there is a T-cell deficiency or not.
Then one can look a little bit deeper and
look at individual subsets of T-cells,
for example look at the number of
CD4+ cells, the number of CD8+ cells.
One can also assess the
function of cells in vitro.
For example, you can stimulate T-cells with a mitogenic
substance called phytohemagglutinin (PHA), or one can stimulate
with specific antigens, one can look for the production of
cytokines such as interleukin-2 in vitro in the laboratory.
One can also look at the function of the immune
system within the individual child using delayed
hypersensitivity reactions to purified protein
derivative (PPD) of Mycobacterium tuberculosis.
Regarding investigation of B-cell primary
immunodeficiencies, again one can enumerate cells.
There are various molecules that
are pretty much restricted to being
expressed on B-cells but not other cells of the immune response.
CD20 is a good example of that.
One can look at cell surface membrane immunoglobulin,
again very characteristic of a B-lymphocyte.
One can also look at the levels of immunoglobulin that are
being secreted into the body of that particular individual.
Regarding the in vivo functioning, one
can look at specific antibody levels.
So as well as measuring total immunoglobulin levels, you
can look at levels of antibody against particular antigens.
For example, isohemagglutinins, antibodies
against E-coli, against tetanus and so forth.
And one may want to immunize those
individuals with non-live vaccines.
It’s very important that anybody suspected
of immunodeficiency is never ever given a
live vaccine, but using bacterial toxins; for
example tetanus toxin or diphtheria toxin.
One can look and see whether the response is adequate
to help identify if there is a B-cell immunodeficiency.
Regarding phagocytic cells, one can count the
number of circulating neutrophils for example.
And there’s also a test that one can carry
out in vitro called the nitroblue tetrazolium
test, which essentially looks at the ability
of neutrophils to mount a respiratory burst.
And in chronic granulomatous disease, there is an inability
to mount a respiratory burst, so this test would pick that up.
And finally, looking at complement deficiencies,
one can use a hemolysis assay to look at the
ability of serum from the individual to lyse red
blood cells, using the membrane attack complex.
If the membrane attack complex is not able to be
produced, that would suggest a complement deficiency.