[achistikbenny]

A 7 months old infant hospitalized for fungal infection does not respond to therapy. He has History of multiple pyogenic infections. Spleen and lymph nodes not palpable. Differential count of neutrophil 95%, lymphocyte 1% and 4% monocyte. Bbone marrow shows no plasma cell or lymphocytes. CXR shows no thymic shadow. Tonsils absent. These presentations is due to which one of the following causes?

A. IL-2 receptor deficiency
B. MHC-II deficiency
C. Adenosine deaminase deficiency
D. Mutation of rag gene

 

[drmodi44]

A??

a.IL-2 receptor deficiency??
fungal infection
multiple pyogenic infection
lymphocyte 1%
no thymic shadow
no plasma cell or lymphocytes in bone marrow all goes in favour of X linked severe combined immunodeficiency
The gene IL2RG located on X chromosome codes for the common gamma chain protein, which is a common subunit of the induvidual receptors for Interleukin 2, 4, 7, 9, 15 and 21. Signalling from these receptors normally promotes growth and differentiation of T-cells, B cells, natural killer cells, glial cells, and cells of the monocyte lineage, depending on the cell type and receptor activated....mutation is caused by large deletions in the IL2RG gene located on X chromosome...

 

[sam01]

C is correct

I think C is the best answer cause the patien have both B and T cell disorder.
Choice A only for t-cell (decrease in Il-2 receptor only decreases t-cell activation
choice B for t-cell again (associated for cd4+ t-cell)
choice D not a specific finding (only for B-cell)
So only deaminase deficiency can cause deficiency in both b and t cells

 

[drmodi44]

....

m not sure...but i think IL 2 receptor defect results in both B and T cell deficiency...its commonest cause of SCID

 

[sam01]

m not sure...but i think IL 2 receptor defect results in both B and T cell deficiency...its commonest cause of SCID

No buddy .Not at all.Il 2 is secreted by Th1 cells and it stimulates cytotoxic T cells.I m 100% sure about that
I know u can get a Scid from an IL-2 receptor defect but i think it affects the developement of CD8+ T cell .But B cell is present but non functionnal because of all those interactions between Il and t and B cells.That s my opinion.Any help please?

 

[drmodi44]

...

its a cause of SCID (severe combined immuno deficiency) means both B and T cell defect...so how can it be only T cell???:notsure:
neways...let achistikbenny answer the Q...

 

[ecgram]

i am so confused with the options



thymus is absent so B & t lymphocytes will be less

so may be C

 

[sam01]

i am so confused witht he options

i knoe its digeorge syndrome chr 22

thymus is absent so B & t lymphocytes will be less

so may be C

it cant be Digeorge cuz u have both B and T cell deficiency.In Digeorge u have only T cell deficiency .And u don t have bacterial infections but only viral and fungal

 

[sam01]

its a cause of SCID(severe combined immuno deficiency) means both B and T cell defect...so how can it be only T cell???:notsure:
neways...let achistikbenny answer the Q...

Maybe u don t understand what i said.All the choices can give SCID.We looking for the best answer here

 

[Seetal]

ADA deficiency is an extremely rare disorder and the child usually dies within a few months (<5) of birth. so i dunno, it could be A (IL-2).

 

[just_md]

Choice A.

All of them produce SCID

Over 50% of cases are caused by gene defect on X-chr resulting in defective IL-2

ADA deficiency is more rare than IL-2 defect

MHC-II deficiency, again, more rare

rag gene mutation - extremely rare condition

 

[achistikbenny]

actually the ans is IL-2 receptor deficiency. i still dont know why it is the ans instead of choice C. The Q was very challenging dt was why i posted it but i can now see dt IL-2 receptor def. is more common than other causes of SCID. Thanks for ur explanations.

 

[sam01]

i still don t get it. They say bone marrow absence of plasma cells ,doesn't it it mean absence of B cells. So ,how could it be IL-2 receptor deficiency bc I know u have B-cell but it s non functional while in ADA deficiency u can't produce it at all. Guys ,go to your first aid 2010 (page 213 -site of block in lymphocyte development). Please tell me what u think cuz I still don t understand

 

[drmodi44]

i still don t get it.They say bone marrow absence of plasma cells ,doesnt it it mean absence of B cells.So ,how could it be Il2 receptor deficience bc i know u have b-cell but it s non functionnal while in ada deficiency u can t produce it at all.Guys ,go to your first aid 2010 (page 213 -site of block in lymphocyte development).Please tell me what u think cuz i still don t understand

as per first aid if we consider only T cell defiency..then also u wont hv plasma cells... as B cell activation in to plasma cells requires IL 4 & IL 5 that r secreted by Th2 cells...refer to kaplan notes...pg 353 2009 edition

 

[inder]

Answer I think is C...
Both IL-2R and ADA deficency lead to SCID. The way you differentiate the two is by their inheritence (IL-2r (XLR), ADA (AR)) and the number of B-cells in the blood.
In ADA def.. purines build up and inhibit ribonucelotide reductase which affects both b-cells and t-cells thus there is no devlopment of either;
Whereas in IL-2R defect the number of b-cells should be normal... as IL-2R and other affected IL-Rs are not needed for B-cell development

REGARDLESS both clinically present the same due to a non-functional immune system;

 

[m82_ghasemi]

Differentiating ADA deficiency and IL-2 Receptor Deficieny

Answer I think is C...
Both IL-2R and ADA deficency lead to SCID. The way you differentiate the two is by their inheritence (IL-2r (XLR), ADA (AR)) and the number of B-cells in the blood.
In ADA def.. purines build up and inhibit ribonucelotide reductase which affects both b-cells and t-cells thus there is no devlopment of either;
Whereas in IL-2R defect the number of b-cells should be normal... as IL-2R and other affected IL-Rs are not needed for B-cell development

REGARDLESS both clinically present the same due to a non-functional immune system;

I would say C is correct.

Abnormal signalling through the IL receptors in X-linked SCID results in many immunological defects, the most apparent of which are severe
disruption of development of T cells and natural-killer cells, and the intrinsic dysfunction of B cells, which are present in normal numbers in many cases.

http://angt.austrianova.com/angt/thrasher scid.pdf

As in this question, the patient had neither plasma cells nor B cells, this exclude IL-2 receptor deficiency. On the other hand, ADA deficiency results in an accumulation of deoxyadenosinehttp://en.wikipedia.org/wiki/Deoxyadenosine,http://en.wikipedia.org/wiki/Adenos...tleAdenosine_Deaminase_.28ADA.29_Deficiency-4 which, in turn, leads to a build up of dATP in all cells, which inhibits ribonucleotide reductase and prevents DNA synthesis, so cells are unable to divide. Since developing T cells and B cells are some of the most mitotically active cells, they are highly susceptible to this condition.

http://en.wikipedia.org/wiki/Adenosine_deaminase_deficiency