[PAGID] pt with recurrent herpes infections and destructive nasal lesion

[Kimberly Risma]

These cases of TAP defects are so rare, I wonder if others who have seen
them wouldn't mind piping in as well as I am very interested in the spectrum
of phenotype. 

In the case of this 19yo, was the "normal" MHC class I expression based on flow cytometry or 
based on HLA serotyping (rarely seen by a junior faculty member such as myself!)?

One thought that I have is to look carefully at his existing CD8 cells-
By testing in vitro CTL function you may have a functional readout of both
MHC presentation through class I and CTL responsiveness, although
an abnormal result will not allow you discern where the defect lies per se.
Second, you can look at the perforin and granzyme content of the existing
CD8 cells. It would be very interesting if you found that your patient was
deficient in these two proteins which are only acquired after conversion 
into effector and/or memory cells. If class I presentation is defective, then
I would anticipate a very naive looking group of CD8 cells, as if he were
a newborn child. 

Kim



Kimberly Risma MD, PhD
Assistant Professor
Allergy Immunology
Childrens Hospital Medical Center
3333 Burnet Ave, mlc 2000
Cincinnati, OH 45229
Kimberly.Risma at cchmc.org


>>> Charlotte Cunningham-Rundles <charlotte.cunningham-rundles at mssm.edu> 4/22/2008 3:21 PM >>>

Although Class 1 found, sounds like TAP defect :  

midline granulomas seem to be a clear part of this syndrome.

Clin Exp Immunol. 2000 Aug;121(2):173-8.  TAP deficiency syndrome.
Gadola SD, Moins-Teisserenc HT, Trowsdale J, Gross WL, Cerundolo V.

(We have a very similar pt)



>We would be grateful for any suggestions/advice on the following case:

>

>19 year old male with history of recurrent herpes viral infections 

>(zoster, oral but not genital) dating back to childhood.  No Candida 

>infections.

>Granulomatous hepatitis with sinusoidal lymphocytosis and splenomegaly

>Present problem - extensive nasoseptal destruction and sinonasal 

>disease.  Temporary response to antibiotics with relapse.  Nasal 

>biopsy from 2006 shows an atypical clonal T-cell (mainly CD4 

>T-cells) infiltration but not felt to be a T-cell lymphoma but more 

>of a reactive clonal process.  2nd nasal biopsy results pending.

>

>CD4 T-cells = 5864/ul and CD8 = 83/ul.  Normal B and NK cell 

>numbers.  Normal Igs (G, A and M) except IgE previously at 738 and 

>more recently at 137.

>Skin boils that  are erythematous papular lesions occurring on the 

>arms, legs, back and sometimes on the face.  These are usually warm. 

>Improvement noted with a topical antibiotic (such as Polysporin). 

> Some growth retardation - thought to be due to chronic disease 

>rather than primary endocrinology problem.

>No skeletal anomalies, abnormal facies or episodic fever or diarrhea.

>MHC class I expression on PBMCs normal.

>

>Thanks,

>

>Miguel Park, MD and Roshini S. Abraham

>

>

>Roshini Sarah Abraham, Ph.D., D(ABMLI)

>Cellular and Molecular Immunology Laboratory

>Department of Laboratory Medicine and Pathology

>Hilton 210 e

>Mayo Clinic

>200 1st St SW

>Rochester, MN-55905

>Ph: 507-266-9292

>Ph (Secy): 507-284-4055

>Fax: 507-266-4088

>



-- 


Charlotte Cunningham-Rundles MD PhD
Professor of Medicine, Pediatrics  and Immunobiology
Mount Sinai School of Medicine
1425 Madison Ave, New York 10029
phone 212 659 9268
fax  212 987 5593
Email:  charlotte.cunningham-rundles at mssm.edu