[CIS-PAGID] B-cell subset question

[Berger, Melvin]

There is an inactivated cell culture-derived Japanese Encepahalitis virus vaccine, Ixiaro, licensed in the US for administration to persons over the age of 17. It is usually given to certain travelers in two doses, 28 days apart. Clinical trials of the use of this vaccine in children are ongoing. ARUP offers ELISAs for IgM and IgG against the virus, but I have no idea of their sensitivity or reproducability. I am trying to find out if anyone knows if there are measureable titers of antibody against the Japanese Encephailitis virus in IgG sold in the US. If not, this may be a good protein neoantigen.
 
Melvin Berger, M.D., Ph.D.
Adjunct Professor of Pediatrics and Pathology
Case Western Reserve University
Cleveland, OH 44106

________________________________

From: pagid-bounces at list.clinimmsoc.org on behalf of Ochs, Hans
Sent: Sat 5/12/2012 10:32 AM
To: <pagid at list.clinimmsoc.org>
Cc: pagid at list.clinimmsoc.org
Subject: Re: [CIS-PAGID] B-cell subset question


Joe's comment - as usual - addresses an important point: to asses the status of the in vivo antibody response capability at the time of testing, a T-dependent "neoantigen" should provide optimal information without the need to stop Ig therapy, or difficulties in interpretation.
We have used bacteriophage for precisely the problem of this discussion: in one such analysis, 5 of 6 individuals on IVIG, for years, had normal primary and secondary Ab responses to phage, including amplification and Isotype switching, and were successfully taken off IVIG therapy.
There are indeed FDA and IRB issues, as with all INDs, but those can be resolved by following certain rules - and our group can assist in this process
Hans

Sent from my iPhone

On May 9, 2012, at 4:39 PM, "Church, Joseph" <JChurch at chla.usc.edu> wrote:



	Hans Ochs' PhiX-174 would be a great option but requires lots of IRB and FDA work to get it authorized at any particular site.  JC

	 

	From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Zachary D. Jacobs, MD
	Sent: Wednesday, May 09, 2012 7:13 AM
	To: <mailto:pagid at list.clinimmsoc.org> pagid at list.clinimmsoc.org
	Subject: 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 < <mailto:charlotte.cunningham-rundles at mssm.edu> 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: <http://Charlotte.Cunningham-Rundles@mssm.edu> Charlotte.Cunningham-Rundles at mssm.edu
	
	
	
	

	
________________________________


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