[CIS-PAGID] B-cell subset question

Seidel Markus markus.seidel at medunigraz.at
Wed May 9 11:13:21 EDT 2012


Dear Zach,

Tick-borne enc.(TBE)-vaccine may be used as (licensed) neo-antigen in order
to test the B cell function under IgG substitution therapy if this sounds
applicable. (see Seidel, Foerster-Waldl et al., 2010
www.ncbi.nlm.nih.gov/pubmed/20656033 )

Best regards from a TBE-infested country,

Markus Seidel



Markus G. Seidel, M.D., Assoc.Prof.

Consultant| Dept.of Pediatric Hematology-Oncology | Univ.Clinics of
Pediatric and Adolescent Medicine | Auenbruggerpl. 34/2 | A-8036 Graz |
Austria | T. 0043 316 385 80215| F. 0043 316 385 13450

Coordinator of the Working Group for Pediatric Immunology of the Austrian
Society of Pediatrics and Adolescent Medicine





_____

Von: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] Im Auftrag von Zachary D. Jacobs,
MD
Gesendet: Mittwoch, 09. Mai 2012 16:13
An: pagid at list.clinimmsoc.org
Betreff: Re: [CIS-PAGID] B-cell subset question



Thanks for the replies. It is a challenging situation for me. I inherited
a large group of his patients he had on IgGRT that fit this general profile,
probably around fifty. The ones who didn't think they ever needed to be on
it were easy to trial off. However, the majority of these patients have
been on therapy for several years and are reluctant to come off. They were
told that without IVIG / SCIG they could die from an infection by someone
who had been practicing for fifty years, and then they hear from me, just
out of training, that they may not need it and so they can become skeptical.
Generally, I have tried to establish a rapport with the patients and a good
doctor / patient relationship before broaching the subject of trialing off.
I have found that if I order B-cell subsets, even with the lack of published
clinical utility for the test, if the memory B-cells are normal in number
then the patient has something to grasp and feels better about trialing off
therapy. I then perform repeat antibody studies when they have been off for
six months.



Any advice on how to better deal with the situation would be much
appreciated.



Zach



On Tue, May 8, 2012 at 5:50 PM, Cunningham-Rundles, Charlotte
<charlotte.cunningham-rundles at mssm.edu> wrote:

In my view the memory B cell phenotype can't be used in substitution of a
complete antibody workup ( off Ig of course) .
I would not use the CD38+IgM or any other combination to assess antibody
production either .

Nice if we had a way around that but this is not it.


Charlotte

Charlotte Cunningham-Rundles, MD, PhD
Departments of Medicine and Pediatrics
The David S Gottesman Professor
The Immunology Institute
Mount Sinai School of Medicine
1425 Madison Avenue
New York, NY 10029
Phone: 212 <tel:212%20659%209268> 659 9268
Fax: 212 <tel:212%20987%205593> 987 5593
Email: Charlotte.Cunningham-Rundles at mssm.edu





_____

From: "Zachary D. Jacobs, MD" <zjacobs.md at gmail.com>
Reply-To: PAGID <pagid at list.clinimmsoc.org>
Date: Tue, 8 May 2012 16:10:17 -0500
To: PAGID <pagid at list.clinimmsoc.org>


Subject: [CIS-PAGID] B-cell subset question

Hello all,


I have been seeing a 52 year-old woman who was started on IVIG about 18
months ago by a now retired immunologist. She had been having recurrent
sinusitis and had frequent courses of antibiotics but she had no imaging
performed during this time, did not have history of sinus surgery and did
not have much in the way of lower respiratory tract infections. Her
quantitative immunoglobulins were normal, except that IgM was consistently
high in the 450 mg/dl range. SPEP was normal. Vaccine testing at the time
showed suboptimal response to PPV-23 with pre-immunization specific antibody
panel showing 5 of 12 serotypes > 1.3 ug/ml and post-immunization it rose to
7/12 serotypes with protective levels. Therefore, she was started on IVIG
by him and she has clinically improved with fewer infections.


I have been evaluating her and would like to trial her off of IVIG. What I
have been doing of late is obtaining B-cell subsets on patients, and if
their memory B-cell counts and frequencies are normal I encourage them to go
off IVIG to see how it goes. For this patient, the frequencies of the
memory B-cells were normal, as were the counts of the switched and
unswitched memory B-cells, but the count of the IgM-only memory B-cell was
elevated at 16 cells/mcl (0-12), and her total IgM(+) B-cell count was
elevated at 395 cells/mcl (37-327) with 87% of CD19 cells being IgM(+). I
thought this was interesting given her historically high IgM counts.


Does anyone have experience in dealing with this particular immunophenotype
and how she would fair off IgG replacement? Should any further work-up be
undertaken?


As an aside and while I'm here writing, this same retired immunologist had
several patients on IVIG with at times soft indications. Since I have been
doing B-cell subsets on these patients I have found several that have normal
memory B-cell counts (switched and unswitched) but had low numbers of
plasmablasts (CD38+ IgM -/+). These patients often have a history of
chronic bronchitis or sinusitis with a mildly low IgG in the mid-400 to
mid-500 mg/dl range, normal IgA and IgM, and mild to moderately impaired
specific antibody responses to PPV-23. What is the clinical significance of
low plasmablasts potentially causing hypogammaglobulinemia, especially in
regards to infectious complications and need for IgG replacement?


Thanks as always,


Zach

--
Zachary D. Jacobs, M.D.
The Center for Allergy & Immunology

Saint Luke's Physician Partners
Medical Plaza II
4330 Wornall, Suite 40
Kansas City, MO 64111

Ph: 816.531.0930
Fax: 816.753.2671

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--

Zachary D. Jacobs, M.D.

The Center for Allergy & Immunology

Saint Luke's Physician Partners

Medical Plaza II

4330 Wornall, Suite 40

Kansas City, MO 64111



Ph: 816.531.0930

Fax: 816.753.2671



CONFIDENTIALITY NOTICE. This e-mail and attachments (if any) may contain
information that is confidential, proprietary, privileged or otherwise
prohibited by law from disclosure or re-disclosure. This information is
intended solely for the individual(s) or entity(ies) to whom this e-mail or
attachments are addressed. If you have received this e-mail in error, you
are prohibited from using, copying, saving or disclosing this information to
anyone else. Please destroy the message and any attachments immediately and
notify the sender by return e-mail. Thank you.



P Please consider the environment before printing this message.





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