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

[Seppänen Mikko]

Dear Richard and Javier,

I should have guessed from which meeting series the data comes from ;=) Again many thanks! Wish I could attend...

Javier's data was interesting indeed!

The Buffalo data is also interesting, Charlotte Cunningham -Rundles has presented similar data earlier in a conference, I think? I have quite a vague recollection only...In her(?) previous presentation (ESID/ECI??) not all serotype-specific titers were corrected to higher "protective" levels despite increased higher dosage (?Charlotte, do I misquote You, hope not?).

The Buffalo abstract does not define "appropriate" doses, i.e. "locally Medicare-approved" or more in the vein of Oxford group ref J Allergy Clin Immunol. 2010 Jun;125(6):1354-1360 (and our practice) where higher dosage (than what I understand is Medicare-approved) is used? Buffalo and Dr Ballow, any comment?
I guess, since those chosen on therapy receive in average higher doses in Europe than in many US states (hearsay?), we probably should redo this Buffalo study in Europe? Before such data, it is hard to make judgment in my patients, based on single measurements. And also one would probably need to measure as many as 23 serotypes (locally I have access to measly 7, about to change soonish)?

Many thanks! I guess I should rethink the 2-6 month dilemma? Richard, do You mostly look for a fourfold titer increase then, not that much for any reached threshold?

mikko

BTW.  Is there going to be a British study on Salmonella vaccine responses to be published some time soonish (rumour)?

________________________________
Lähettäjä: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] Puolesta Richard Wasserman
Lähetetty: 10. toukokuuta 2012 16:26
Vastaanottaja: pagid at list.clinimmsoc.org
Aihe: Re: [CIS-PAGID] B-cell subset question and IgE

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<mailto: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> [mailto: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<mailto: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<mailto:Mikko.Seppanen at hus.fi>
To: pagid at list.clinimmsoc.org<mailto: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<tel:%2B358%209%2047175923>, fax +358 9 47175945<tel:%2B358%209%2047175945>

_________________________________________



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



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Richard L. Wasserman, MD, PhD
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DallasAllergyImmunology
7777 Forest Lane, Suite B-332
Dallas, Texas 75230
Office (972) 566-7788
Fax (972) 566-8837
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