[CIS-PAGID] B-cell subset question

[Cunningham-Rundles, Charlotte]

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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