[PAGID] ?Unique XHIM patient

[Church, Joseph]

Thank you for your thoughts.  I think that is a great idea.  JC

-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Dewton
Vasconcelos
Sent: Thursday, July 22, 2010 4:55 AM
To: pagid at list.clinimmsoc.org
Subject: Re: [PAGID] ?Unique XHIM patient

Dear Joe, good morning

After all these very interesting comments I wondered about the real need

of IVIg in this patient. If he hadx normal IgG levels before IgG 
replacement, is he really a candidate for replacement? I remember that 
you said that you do not have the previous serologies. How about testing

him with PhiX174 immunization to unravel his capacity of responding to a

new antigen?

Dewton Vasconcelos
University of Sao Paulo Medical School

Church, Joseph wrote:

> 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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