[CIS-PAGID] B-cell subset question

[Sullivan, Kathleen]

rabies!  It's a tough sell but also a neoantigen and it is really not so bad.  Two of our immunologists had bat exposures and had the vaccine and it had very limited side effects.

Kate
On May 9, 2012, at 11:22 AM, Fleisher, Thomas (NIH/CC/DLM) [E] wrote:


> This vaccine is not available in the US as far as I know.

>  

> Thomas A. Fleisher, M.D.

> Chief, Department of Laboratory Medicine

> NIH Clinical Center

> 301 496-5668 (T)

> 301 402-1612 (F)

> From: Seidel Markus [mailto:markus.seidel at medunigraz.at] 

> Sent: Wednesday, May 09, 2012 11:13 AM

> To: pagid at list.clinimmsoc.org

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

>  

> 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: 212 659 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 sender by return e-mail. Thank you.

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Kate Sullivan, MD PhD
Professor of Pediatrics
ARC 1216 Immunology CHOP
3615 Civic Center Blvd.
Philadelphia, PA 19104
(p) 215-590-1697
(f) 267-426-0363


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