[PAGID] Patient with lymphopenia

[Jack Bleesing]

Morning Folks:

- Don't forget in vitro delayed skin tests as a functional T-cell
function test (and bypassing the lack of CD4 T-cells)

- Would be interested in more detailed immunophenotyping of her lymphs
(Forms Follows Function)

- PNP deficiency: screening tool = low to absent uric acid levels

- Atypical WHIM? (reduced naive and central memory T-cells, see
Blood;102:444, 2004).

- B-cell phenotype/increased transitional?; IL-7 levels? (see Blood,
109;2086, 2007)

- we have seen several patients with "leaky SCID" phenotype with
presumed mono-allelic IL-7R mutations and auto-immunity (true, true and
unrelated?). Mono-allelic other SCID genes could be considered as well,
as we have a fairly convincing CID patient with mono-allelic JAK3
mutation (same as seen in classic SCID); fairly convincing because she
might have something else as well - related to growth-hormone
insensitive growth delay.

- autoantibodies to T-cells, as seen in SLE and ALPS (perhaps)?;
preserved function and immunophenotypic clues

Regards,

J

---------------------------------------------------------------------------
Jack J.H. Bleesing, M.D., Ph.D.
Cincinnati Children's Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Avenue, MLC 7015
Cincinnati, OH 45229
513-636-4266 (phone)
513-636-3549 (fax)
Jack.Bleesing at CCHMC.org
http://www.cincinnatichildrens.org/immunodeficiencies/



>>> "Luigi Notarangelo" <luigi.notarangelo at childrens.harvard.edu>

4/21/2008 8:43 AM >>>
Dear Jason:

Indeed, a very interesting patient.

While idiopathic CD4 lymphopenia would have to be considered, as
already
mentioned by others, I agree with Dale Umetsu that any form of ³leaky
SCID²
might result in a similar phenotype.
A few years ago, we reported on a family with JAK3 deficiency in which
late
diagnoses were made based on warts and lymphopenia (Frucht et al, Genes
and
Immunity, 2001; 2:422) in some, but not all, affected family members.
I agree with Melvin that functional assays would be important in a case
like
yours. One way to overcome the issue of T cell lymphopenia would be to
label
in vitro cells with CFSE prior to the culture and then follow
specifically
proliferation of the T cells in response to PHA (and also to anti-CD3
alone
or with IL-2) by looking at dilution of CFSE gating on the CD3+
population.
You might even use this approach to investigate whether you have
increased
cell death during the culture, by staining for annexin V.

Very interesting! Please, keep us updated!

Gigi


Luigi D. Notarangelo, M.D.
Director, Research and Molecular Diagnosis Program on Primary
Immunodeficiencies
Division of Immunology, Children's Hospital
Professor of Pediatrics and Pathology, Harvard Medical School
Karp Building, 9th floor, Rm 09210
1 Blackfan Circle
Boston, MA 02115
USA

(tel) (617)-919-2276
(fax) (617)-730-0709


Secretary: Luisa Raleza
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