[CIS-PAGID] B-cell subset question and IgE

[Javier Chinen]

We presented this work at the First Clinical Immunological Society, positive responses were evident. All were SCID post BMT. Not published as we were gathering more patients and tried other conditions.Thanks,Javier

Evaluation of antibody responses of SCID patients post-bone
marrow transplant while receiving IVIg 

 

Aracely Vasquez, Howard M. Rosenblatt, I.
Celine Hanson, Robert A. Krance, William T. Shearer, Javier Chinen

Allergy and Immunology Section and Bone Marrow Transplant
Unit, Department of Pediatrics, Baylor College of Medicine, Houston, TX

 

Background:  Current guidelines recommend administration of
inactivated vaccines 6-12 months after bone marrow transplant (BMT). In
congenital immunodeficiencies patients, however, the ability of specific
antibody responses may not be restored at this time. Usually, these patients have
received immunoglobulin supplementation (IVIg) since diagnosis and the time of
safe IVIg discontinuation is also uncertain. We sought to demonstrate antibody
responses to common vaccines in these patients while receiving IVIg. 

Methods: Anti-tetanus,
-diphtheria and –pneumococcal immunizations were given two weeks after IVIg infusions.
We measured serum immunoglobulin concentrations and specific antibody titers before
and after immunizations in 11 SCID patients at least 12 months post-BMT. History
of graft-versus-host-disease (GvHD), chimerism, lymphocyte phenotype and SCID B
cell type were recorded.  

Results: We studied
eight B+ SCID and three B- SCID patients. Ten of 11 patients demonstrated sustained
logarithmic increases of anti-diphtheria, anti-tetanus and anti-pneumococcal specific
antibody titers after immunization. These responses were evident after the
second immunization dose. Antibody titers for only the anti-pneumococcal
serotypes included in the vaccine increased. The patient who did not respond
was a B+ SCID, received a conditioned, HLA-haploidentical (mother) BMT at one
month of age, did not develop GvHD, and had a 19% donor B cell chimerism at
last immunization dose. His IgA and IgM levels were within normal range. Transient
IVIg discontinuation in this patient was associated with increased frequency of
infections.

Discussion:
Immunization with inactivated vaccines can identify
patients post-BMT with incomplete immunoreconstitution while still receiving
IVIg. We recommend this practice to avoid premature discontinuation of
infection prophylaxis measures.

Javier Chinen, MD, PhD 
Phone cell (281)825-2561
 From: Mikko.Seppanen at hus.fi
To: pagid at list.clinimmsoc.org
Date: Thu, 10 May 2012 08:14:32 +0300
Subject: Re: [CIS-PAGID] B-cell subset question and IgE

















Dear all

 

Richard, You
refer to data on response testing while on therapy that I at least am not aware
of, could You please give a reference? I do have tried testing 2-3 months later
and found myself struggling with reliability issues (real or unreal), and my
patients do yet again wait for 6 months. Thus if any data, I would appreciate it
as well. Half life / consumption of IgG can be very variable in patients and is
different in healthy vs. agammaglobulinemic?

 

TBE-vaccines (Encepur,
Ticovac) are proteins, just like rabies. Thus a bit problematic if
response is + but pt fits CVID phenotype: as You all know, it is not that rare
to see (a short lasting but) nice T-B response to strong T-B antigens (tetanus)
while e.g. diphtheria (and Pneumovax of course) are missing and the patient is
a typical CVIDs pt in all regards otherwise. 

Since I give TBE and even rabies (travelers) vaccines  more or
less regularly (being an ID doctor) I have not seen nor heard nor read of any
real safety issues (occasionally 2.-3. rabies vaccine gives relatively severe
local reaction), aside from an occasional MS patient, where the issue of safety
with protein antigens remains unsolved but the more recent consensus considers
them most likely safe. Polysaccharides are BTW safe, thus no contraindication
to test an MS pt with Pneumovax.

 

There is also a very tolerable Japanese Encephalitis vaccine
(Ixiaro) now in the market (in US as well?), the older vaccine had real safety
issues… however, early Ixiaro responses can be very variable in normal
population (my colleague A Kantele has studied and probably already published
on that), thus 2 vaccine shots are needed. 

 

Measuring IgE has
helped me, since appr. 90% of CVIDs in our patient material do not produce IgE  (?
does anyone have an exact figure in a large material?) and thus if it indeed is
immeasurable, adds credence.

 

And Zachary, I have been through the same for the last 15 years,
even more so for the last 5, so if You come to ESID Florence, we might both
find a discussion therapeutic! And my hair’s been very gray for >10
years now... so dyeing might not help… but You are not alone! My warmest appreciation
for doing what You do!

 

mikko

 

BTW Nobody was eager to comment on IgG2D?

 

_________________________________________________

Mikko Seppänen, MD, PhD, Docent (Associate professor/Senior
Lecturer) 

Specialist in Internal Medicine and Infectious Diseases

Senior Consultant, Physician in charge (PIDD)

EM(E)A Expert, PIDDs and Intravenous Immunoglobulin Therapy

 

Immunodeficiency Unit

Division of Infectious Diseases

Department of Medicine

Helsinki University Central Hospital

Hospital District of Helsinki and Uusimaa

Aurora Hospital, Ward 4-2 and Outpatient Clinic

P.O.Box 348

FI-00029 HUS, Helsinki

FINLAND

phone +358 9 47175923, fax +358 9 47175945

_________________________________________

 



Lähettäjä: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] Puolesta Richard Wasserman

Lähetetty: 9. toukokuuta 2012 17:18

Vastaanottaja: pagid at list.clinimmsoc.org

Aihe: Re: [CIS-PAGID] B-cell subset question



 

Given the half life of IgG and
the recent data suggesting that you can evaluate pneumococcal polysaccharide
response while on therapy, there is no need to keep them off for six months. I
would get new baseline studies two months after the last IGIV treatment and
vaccine at that time. It may be more palatable.

Richard Wasserman



On Wed, May 9, 2012 at 9:13 AM, Zachary D. Jacobs, MD <zjacobs.md at gmail.com>
wrote:

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: 212 659 9268

Fax: 212 987 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
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-- 

Richard L. Wasserman, MD, PhD

DallasAllergyImmunology

7777 Forest Lane, Suite B-332

Dallas, Texas 75230

Office (972) 566-7788

Fax (972) 566-8837

Cell (214) 697-7211

 		 	   		  
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