[PAGID] IPEX like 7 month old

[Luigi Notarangelo]

Jack,

You are probably right, however I think there are still too few data in this
regard.
However, one important point is that also for nTRegs one should probably
look at absolute numbers. I am currently studying a mouse model of
hypomorphic lig4 deficiency, in which thymic output is obviously severely
reduced, but the ability to generate Foxp3+ T cells in the thymus is spared,
if measured as a fraction of CD4 SP thymocytes (but is markedly reduced if
absolute numbers are considered). However, as I said, I don't think there
are enough data (neither in mice or in humans) there to support the number
of Foxp3+ T cells as a measure of thymic output.

Luigi D. Notarangelo



On 1/10/08 1:41 PM, "Jack Bleesing" <Jack.Bleesing at cchmc.org> wrote:


> Luigi:

> 

> In that list, wouldn't FOXP3+ T-cells belong as well, as a marker of thymic

> function (at least in our patient population with abnormal thymic production,

> whether through a stem cell defect or thymus defect?

> 

> We find few if any FOXP3+ T-cells (and one has to look at absolute numbers,

> not percentage of CD4+ or CD4/CD25, etc).

> 

> Happy new year to all!

> 

> JB

> 

> ---------------------------------------------------------------------------

> 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> 1/10/2008

>>>> 1:36:30 PM >>>

> I agree. Functional studies are very important. It is now clear that Omenn

> syndrome is truly a syndrome, and there are more and more cases repoertd who

> retain B cells. Thus, I would not disregard at all this possibility. I would

> suggest that you look not only at PHA response (which is obviously defective

> in SCID with maternal engraftment, but can occasionally be normal in Omenn

> syndrome), but also at proliferation to anti-CD3 (more consistently affected

> in patients with Omenn).

> I would also strongly suggest to look at the following:

> 

> A) CD45RA vs CD45R0 on T cells

> B) TRECs

> C) T cell repertoire either by FACS (looking at expresed TCRBV families) or

> by spectratyping looking at CDR3 length

> 

> These assays should clarify the possible diagnosis of SCID or Omenn.

> 

> Luigi D. Notarangelo

> 

> 

> 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

> email: luisa.raleza at childrens.harvard.edu

> 

> 

> 

> 

> On 1/10/08 11:51 AM, "kumar036 at umn.edu" <kumar036 at umn.edu> wrote:

> 

>> Dear Friends,

>> 

>> I am looking for help with a 8 month boy who has severe eczema, failure to

>> thrive and significant eosinophilia. His total white count is 25-30 with

>> 25% eos, giving him an absolute eosinophil count of 7000. He has widespread

>> eczema which on biopsy showed infiltration with eos and lymphocytes. Total

>> B, T and NK numbers are in the normal range with a CD4 to 8 ratio of 6. IgG

>> of 200, and IgE of 70. IgA and IgM are normal (31). He has had watery

>> diarrhea since birth, weighs only 5 Kg (at 8 months), no diabetes or

>> thyroid dysfunction. Given this picture, I suspected IPEX even though he

>> has no endocrinopathy, but his FOXP3+ CD4s are normal in number.

>> 

>> Where do I go next with this picture? There is no positive family history.

>> I am waiting maternal engraftmetn studies, in case this is SCID or Omenn

>> with maternal engraftment. I also just found that his CH50 is 0, with

>> normal C3 and C4 levels. I am going to repeat the CH50 and get C2 and C5

>> levels. There are few papers from the 70s describing Leiner's disease with

>> C5 deficiency that causes eczema and failure to thrive. His hair looks

>> normal and he doesn't have any teeth yet. He does not look dysmorphic and

>> hasn't had any infections besides a couple URIs.

>> 

>> Ashish Kumar

>> University of Minnesota

>> 

>> 

>> 

> 

> 

> 

>