[PAGID] ? Possible SCID

[Junker, Anne]

We had boy present at age 8 weeks with AIHA unresponsive to steroids and
IVIg. Prior to 4 doses of Rituximab 375 mg/m2/dose) the CD3 count was
1.75 (2.3-6.5) with proportionately decreased CD4 and CD8.  Normal
numbers of NK cells.   At 10 days after the 4th dose of Rituximab the Hb
was normal, B cells were absent and CD3 count was 1.8.  One week later
the child presented with fulminant PCP and ARDS.  He was in ICU on
ventilation for 3 months and in hospital a 4th month being weaned from
oxygen.  The first mitogen studies at the start of this illness were
profoundly low. ADA and PNP studies were normal.   As he recovered,
mitogen studies normalized.  Now at age 1 year he has recovered his B
cells.  His T cell counts and mitogen studies are normal.  His AIHA
remains in remission.  He is growing and developing normally.   We
elected to defer further immune studies at the time of his acute
illness, because transplant was not an option with his critical
condition.  Now that he has recovered, we suspect his PCP was a
complication, as has been described, of Rituximab therapy.
 
Anne Junker, MD
Associate Professor, Division of Infectious & Immunological Diseases
BC Children's Hospital
Vancouver, BC, Canada
604-875-3591
ajunker at cw.bc.ca
 
 

________________________________

From: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Kathleen E.
Sullivan
Sent: Saturday, February 21, 2009 6:23 AM
To: pagid at list.clinimmsoc.org
Subject: Re: [PAGID] ? Possible SCID


This is very bizarre but I had a patient with EXACTLY that phenotype.
She/he was worked up extensively and no gene defect was found but
eventually her autoimmune disease became nearly uncontrollable and she
received a BMT.  She has done very well since then. 

Kate

Kathleen E. Sullivan MD PhD
Chief, Division of Allergy and Immunology
Professor of Pediatrics
The Children's Hospital of Philadelphia
(p) 215-590-1697
(f) 267-426-0363


On Feb 20, 2009, at 5:16 PM, Abraham, Roshini S., Ph.D. wrote:


	
	On behalf of Dr. Aly Mageed:
	
	
	Dear PAGID colleagues,
	
	I am seeking some input/advice with regards to the following
case:
	
	Patient is a 7 month old WF (DOB 6/30/08), half a non identical
twin, who presented at 6 weeks with severe Coomb's + AIHA (Warm + IgG
and C3) (Hgb of 2.5 gm) and WBC was 32,000 while ALC was 5,491 (stayed
1700-2470 for the next 12 days and later she had only 2-7% lymphs with
ALC of around 500) and had to be emergently exchange transfused with non
irradiated blood. No earlier CBC's are available. She was then started
on steroids 3mg/kg/day and weekly Vincristin (got 16 doses). Prednisone
was tapered (was on 3mg/kg from 8/10-->10/16, 2/k till 11/26, 0.7 mg/kg
till 12/24). She then presented on Dec 24/2008 with PCP pneumonia
despite Pentamidine Px. PCP was treated successfully with Bactrim 20mg/k
from 12/24-->1/15 with re-increase of Pred. to 2.2mg/kg until12/30,
1.5/k until 1/ 4 and 1mg/k till 1/9, 0.7mg/kg until 1/9 and 0.25 mg/k
until 2/1/09.
	
	Lymphocyte subpopulations were done on January 16 and showed low
WBC in general at 1700 (was on Pred. and Bactrim as above) ALC was 417,
CD19=15, CD3= 94, CD4= 38, CD8= 46 and CD16/56= 304. She started having
a skin rash and diarrhea with FTT. Rash disappeared upon increasing
steroids to relapse upon its taper. Bx was suggestive of mild GVHD in
gut and skin (was under steroid and cyclosporine) with CD4 and CD8
infiltration.
	
	While looking for XY to rule out TA-GVHD we found out that she
is constitutionally XY with testicular feminization. The blood donor was
a male who is now undergoing STR analysis to R/O TA-GVHD. IgG was 687,
M= 97 on 9/25 (after IVIG therapy for AIHA) but IgG was 180, M was 111
on 1/16 and IgG was 383 on 1/29. HIV is negative. Mitogen stimulation
was very low at 2-3% of NC (maximal cpm of ~4000 on a background of 130
for PHA/ ConA) (but was on steroids/VCR as above).
	
	Repeat Lymph subpopulations on 2/10 showed WBC of 2,700, ALC =
355, CD19=37, CD3= 215, CD 4=149, CD8= 63 and CD16/56 = 103. Last CBC
showed 3000 WBC and ALC = 780, on steroids.
	
	BM showed mild/moderate hypoplasia with marked lymphopenia.
Isohemagglutinin was low at 1:2, (she is O-). Gut and skin x
suggestive+/- GVHD changes on treatment.  PNP is unlikely with NL uric
acid and ADA-B level was NL. Genetic testing is pending for RAG1/2,
JAK-3, Artemis, IL2RG. Also, we did not find any XX cells for possible
maternal engraftment on skin biopsy or blood.  The questions are:
	

	1.	Do we have enough clinical evidence for a diagnosis of
SCID without having to wait for molecular diagnosis? She has a matched
sib to move to BMT right away. 
	2.	Or, is she having an iatrogenic immune deficiency caused
by almost a life long therapy with steroids/VCR which can cause
lymphopenia, and her leukopenia is Bactrim related? Her presentation
with AIHA is possible/rare with SCID and usually it is a late
manifestation rather than presenting Sx. 
	3.	Interestingly the testicular feminization gene is close
to SCID on the X chromosome. I am still looking for the donor STR
markers in her to R/O TA-GVHD. 
	4.	I will repeat the Mitogen Stimulation on only
physiologic dose of steroids and if low again move to BMT with or
without gene proof. We are also going to do array CGH and TREC/RTE
analsysis for evidence of thymic activity. 
	5.	The other question is would conditioning be appropriate
with recently reduced low NK cells as well?

	
	I would greatly appreciate any advice or comments on this
challenging case.
	
	
	Aly Mageed, MD, MBA
	Division Chief, Pediatric Blood & Marrow Transplant Program
	Director, Stem Cell Engineering Laboratory
	Helen DeVos Children's Hospital, Spectrum Health
	Associate Professor of Pediatrics, Michigan State University
	100 Michigan street NE
	Grand Rapids, MI 49503
	MC#185
	
	(616)-391-3962
	aly.mageed at spectrum-health.org
<mailto:aly.mageed at spectrum-health.org> 
	
	
	
	

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

	Director 
	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

	


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