[PAGID] ?Unique XHIM patient

[Church, Joseph]

James:

The patient came to me after all of these developments, so I don't have
any of the standard markers for MAS.

The mutation is unique, but the patient's CD40L expression is very low -
only on 1% of activated CD3+CD4+ cells.  So, I think it's real.

JC

-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Verbsky, James
Sent: Tuesday, July 20, 2010 6:20 PM
To: pagid at list.clinimmsoc.org
Subject: Re: [PAGID] ?Unique XHIM patient

Dr Church

Do you have levels of ferritin, triglycerides, fibrinogen, or CD25?  Are
there anti-neutrophil antibodies??  I have personally never seen MAS
present with only one cell line down, and if the ferritin isnt above
1000(or more likely 5000), I would find it unlikely that this is
MAS/HLH.  Surprising that this childs IgG is normal and that there is no
history of infections.  Has this mutation been described??

Best of luck

James

James Verbsky MD/PhD
Assistant Professor of Pediatrics and Microbiology and Molecular
Genetics
Medical College of Wisconsin
Milwaukee, WI  53226

________________________________
From: pagid-bounces at list.clinimmsoc.org
[pagid-bounces at list.clinimmsoc.org] On Behalf Of Church, Joseph
[JChurch at chla.usc.edu]
Sent: Tuesday, July 20, 2010 3:17 PM
To: pagid at list.clinimmsoc.org
Subject: [PAGID] ?Unique XHIM patient

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