[PAGID] rituximab vs PID

[Jung, Lawrence]

I am not sure that you have evidence for T cell functional deficiency.  The abnormal PHA response may be due to low # of T cells in the PBMC and not to T cell functional deficiency.  Have you isolated his T cells to see whether they respond to mitogenic and antigenic stimulation or expression of CD69 by flow cytometry?  If the T cells are indeed functionally deficient, then there is more of a case for PID.

While steroid therapy may suppress T cell function to a degree, in my experience, it is usually >50% of normal.

Larry Jung
Omaha, NE

-----Original Message-----
From: pagid-bounces at clinimmsoc.org [mailto:pagid-bounces at clinimmsoc.org] On Behalf Of Rhoda Kagan
Sent: Tuesday, August 16, 2005 7:58 AM
To: pagid at clinimmsoc.org
Subject: Re: [PAGID] rituximab vs PID


Thanks for your thoughts.
He does not have any significant adenopathy, so it seems like ALPS is
unlikely.
Regarding CGD, we did measure function with a fluorescent assay, so
although we could pursue further with gene testing, we don't have much to
suggest this a phagocyte disorder.
The T cell #s and function have remained low despite complete radiologic
and surgical assessment of the mucor.  He has been debrided and looked at
several times noting NO further disease, but we are reluctant to stop
anti-fungals given the ominous prognosis of this infection. Having said
this, can we still accept this degree of T cell dysfunction based on the
infection?





Kathleen E.Sullivan <sullivak at mail.med.upenn.edu>@clinimmsoc.org on
08/16/2005 08:16:18 AM

Please respond to pagid at clinimmsoc.org

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Subject:  Re: [PAGID] rituximab vs PID




I have seen results of T cell studies in lupus patients after multiple
courses  of rituximab and there was no effect on T cell numbers so I
would be reluctant to ascribe the effect to rituximab.  I have a few
ideas in terms of his process that perhaps you have already addressed.
He can't really have SCID and be 11 years old so I presume you are
asking whether he could  have such significant T cell dysfunction that
he warrants a transplant.  I would wager that some degree of T cell
dysfunction is as a consequence of his fungus and you will see some
modest improvement over time.  Hard to believe he was born with this
degree of compromise and has had only AHA until now.   I know you have
tested for CGD but the NBT is not sensitive for mild mutations and CGD
patients can have low T cell numbers and function that can worsen after
fungal infections.  CGD would tie a lot of the features together so it
might be worth retesting with a more sensitive fluorescent assay.  My
last thought is whether he has had much adenopathy and should be tested
for ALPS.   The caspase deficient forms can look a lot like CVID and
have some unusual infections and could go along with AHA.

On Aug 15, 2005, at 4:12 PM, Rhoda Kagan wrote:

> Any suggestions as to the  management or diagnosis of this child are
> welcome!
>
>
>  11 yo Asian boy  with invasive murcormycosis following a course of
> rituximab for refractory autoimmune hemolytic anemia.  Subsequent
> immune
> work up noted T cell lymphopenia and poor T cell function.  Is this a
> result of rituximab? If so, should we anticipate some improvement (it
> has
> now been a year since last dose!) or did he have an undiagnosed PID
> without
> any significant infections until last year?? Our questions are
> twofold: 1.
> must he continue on anti-fungal treatment indefinitely (our ID
> colleagues
> have suggested that he should); 2. should we consider BMT if he is
> SCID?
>
> History:
>      -Born to non-consanguineous parents
>      - Thal Major dx'd at  8 mos;  autoimmune hemolytic anemia
> diagnosed in
>      the first year of life
>      -transfusion-dependent with multiple transfusion reactions,
> including
>      severe hemolysis, (Anti-Lu a Ab positive), initially managed with
>      pre-treatment  solucortef
>      *2003, hemolysis worsened;transfusion requirement
>      increased?..Prednisone commenced 10-40 mg qd
>      *2004, rituximab  (total 3 doses). Last dose july 2004 & IVIG q 4
>      weeks
>
>      -Sept. 2004: Mucormycosis infection of maxillary, ethmoid, and
>      sphenoid sinuses as well as peri-orbital region, treated with:
>      local and systemic amphotericin,  posaconazole, local irrigation
> and
> regular debridement, hyperbaric O2 (38 courses),  and G-CSF
>
>      -Current management/disease status (presently radiographically
> disease
>      free)
>      Posaconazole,  Prednisone , Septra prophylaxis, transfusions as
> required
>
> Immunology Work up  (all investigations done post-rituximab and
> unchanged
> on repeat testing)
> HIV negative
> NBT, complement:  normal
>
> CBC: WBC 3.6  Hgb 63 Plt Nl  ANC 2.3 ALC 0.8
> CD3 0.487 CD19 0.639  CD4 0.070  CD8  0.320 NK 0.139
> PHA SI 1.22
> IgG 9.82 (on IVIG); IgM 2.10 IgA 2.26
>
>
> Rhoda Kagan, MD
> Montreal Children's Hospital
> rhoda.kagan at muhc.mcgill.ca
>
>
>
>
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Kathleen E. Sullivan MD PhD
Associate Professor of Pediatrics
The Children's Hospital of Philadelphia
(p) 215-590-1697
(f) 215-590-3044






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