[CIS-PAGID] (no subject)

[Verbsky, James]

T cell mitogens?  The diabetes and autoimmune enteropathy would definitely point toward a Treg defect.  If mitogens low..might consider CD25 deficiency/IL2 deficiency.  Might be helpful since that treatment is transplant

In these cases, polytherapy is needed.  Has she been on steroids, imuran, and CSA together or all individually.  Agree with Chris' comment on rapamycin..again I would add meds till she improves.  For lung disease in CVID we have had some success with Imuran and Rituxan..not sure about gut disease.

I assume her low Ig is PLE..but what is her albumin

You might talk to Troy Torgersen..I would treat this person like an IPEX as she is certainly not responding like an IBD




James Verbsky MD/PhD
Associate 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 christian.wysocki at yale.edu [christian.wysocki at yale.edu]
Sent: Wednesday, February 22, 2012 4:47 PM
To: PAGID
Subject: [CIS-PAGID] (no subject)

We have a really sick young lady, 24 years old with CVID, enteropathy and other
autoimmune sequelae.  Her enteropathy has been severe for many years and
refractory to numerous immunomodulatory therapies as detailed below.  She has
required TPN since september 2011.  We are hoping to get opinions as to any
therapies for severe, refractory CVID associated enteropathy, that people have
had success with...we are particularly interested in Rituximab, and wondered
what peoples experience with it were, but are open to any and all suggestions.
Please see a more detailed clinical description below.

Severe chronic diarrhea since age 3.  Biopsies in the past showed a celiac-like
process with villous blunting in the small bowel and lymphocytic infiltrates
(primarily CD3+....don't know CD4 or 8) in small and large bowel.  She failed a
gluten-free diet, and was somewhat improved on prednisone and Imuran.

In adolescence, she developed a bad pneumonia, and recurrent sinusitis, and was
referred to us when total IgG, A and M were found to be undetectable (total IgG
had been 1500, IgA <7 when tested at age 3).  In the meantime, she had
developed type 1 diabetes and JRA.  She has been on Ig replacement since...made
more difficult by GI protein loss causing difficulty maintaining troughs.  She
is now on Hizentra and doing better from that perspective. We have done
numerous flow analyses over the years....initially B total B cells were quite
low (27/ul), but those have come up to normal more recently.  We did a detailed
analysis 2 years ago, which showed almost no class switched memory B cells,
normal CD21.

The GI process still rages out of control, such that she has been on TPN since
September.  The GI docs have tried numerous immunomodulatory agents over the
years which seem to provide only transient, if any, benefit, including oral
steroids (which she is now on chronically), Imuran, cyclosporin, Remicade,
Humira and most recently, Cimzia.  A 6 month trial of Cimzia has failed.

Thanks for any help or advice you can provide,
- Chris Wysocki, Yale Allergy and Immunology fellow