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

[Richard Wasserman]

An Evaluation of Pneumococcal Titers in Patients receiving Ig replacement
for Immunodeficiency
A. Shvarts, M. Ballow, A. Yu, H. Lehman
February 2012     Journal of Allergy and Clinical Immunology Vol. 129,
Issue 2, Supplement, Page AB84

I have reevaluated after two months off therapy for many years and have not
had problems. Of course, the numbers, regardless of when they are obtained,
should be evaluated in the context of previous clinical and laboratory data.
Richard Wasserman

On Thu, May 10, 2012 at 6:33 AM, Seppänen Mikko <Mikko.Seppanen at hus.fi>wrote:


> **

> Greatly appreciated!!!!

>

> Many thanks!

>

> mikko

>

>  ------------------------------

> *Lähettäjä:* pagid-bounces at list.clinimmsoc.org [mailto:

> pagid-bounces at list.clinimmsoc.org] *Puolesta *Javier Chinen

> *Lähetetty:* 10. toukokuuta 2012 14:27

> *Vastaanottaja:* pagid at list.clinimmsoc.org

> *Aihe:* Re: [CIS-PAGID] B-cell subset question and IgE

>

>  powerpoint of the presentation. CIS2010.

>

> Thanks

>

> Javier Chinen, MD, PhD

>

>

>  ------------------------------

> 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 <http://gmail.com>>

> *Reply-To: *PAGID <pagid at list.clinimmsoc.org <http://list.clinimmsoc.org>>

> *Date: *Tue, 8 May 2012 16:10:17 -0500

> *To: *PAGID <pagid at list.clinimmsoc.org <http://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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>

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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.

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> P *Please consider the environment before printing this message.*

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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

>




-- 
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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