[PAGID] ?Unique XHIM patient

[Church, Joseph]

Thank you all for your very helpful comments.  Joe Church

-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Conley, Mary
Ellen
Sent: Wednesday, July 21, 2010 11:33 AM
To: 'pagid at list.clinimmsoc.org'
Subject: Re: [PAGID] ?Unique XHIM patient

Hi Joe,
I would guess that most of my colleagues will disagree with me but I
would not push for transplant in this patient.  His mutation in CD40L
would be considered a mild mutation - it is likely that it impairs but
does not ablate correct splicing of the message.  His normal IgG and
lack of infections also suggests milder disease.  I doubt the
neutropenia is due to hematophagocytic syndrome.  There are old data
indicating that stromal cells express CD40 and secrete G-CSF in response
to CD40L.  However, only some patients with CD40L deficiency have
neutropenia.  Maybe we can blame the modifying genetic factors?  Most of
the push for transplant in patients with CD40L deficiency comes from the
European review that showed that patients had a high incidence of crypto
and sclerosing cholangitis and a high incidence of death in the 3rd
decade.  The crypto does not seem to be as common in CD40L deficient
patients in the US.
Mary Ellen





Mary Ellen Conley, MD
Department of Immunology/ Mail Stop 351
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678
FAX  901-595-3977
TEL  901-595-2576


-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Kimberly Risma
Sent: Wednesday, July 21, 2010 9:55 AM
To: pagid at list.clinimmsoc.org
Subject: Re: [PAGID] ?Unique XHIM patient. .

Does he have antibody titers to vaccines?
Have you tested more than one Ab for CD40L (including the CD40:FC
reagent)?
Because sometimes one Ab will not recognize the epitope of the protein
but another will. We can help you with this if need be, 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


>>> "Church, Joseph" <JChurch at chla.usc.edu> 7/20/2010 4:17 PM >>>

Colleagues:



I am seeing an 11yo boy with XHIM for a second opinion regarding
management.



*       He has had no infections indicative of B-cell/antibody
deficiency.
*       He has had intermittently severe neutropenia since 2yo, now
requiring increasing doses of G-CSF.
*       His IgG and IgM levels prior to IVIG therapy were normal; IgA
was undetectable.
*       1% of activated CD3+CD4+ express CD154.
*       He has a novel mutation: 290(-7) T>G in the splicing receptor
site of intron 2.
*       A recent bone marrow showed "cellular marrow with trilineage
hematopoiesis; left shifted granulopoiesis."
*       Two sibs are not HLA matches.



Could the neutropenia be autoimmune?



Does hemophagocytic syndrome/macrophage activation syndrome cause
unilinear (in this case granulocyte) cytopenia?



I think HSC transplant is still indicated.  Would anyone disagree?



Thank you for your help.



Joe Church

Childrens Hospital Los Angeles








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