[CIS-PAGID] B-cell subset question

[Saxon, Andy M.D.]

"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.  She was started on IVIG by him and she has clinically improved with fewer infections."

Without any imaging, the diagnosis of recurrent sinusitis is highly suspect with essentially normal Ig's and getting "better" on IVIg is a huge placebo.  Frankly I don't know what to make of her IgM levels and IgM cells but I'd certainly want to try to get off IVIg.. I assume this immunologist made sure she was not allergic...  If not, clearly must be done.  I would look for a small clinically insignificant paraprotein MGUS on given patients age IEP as it could be missed on SPEP and this may account for IgM changes.

Key is going to be imaging to try to get an objective handle on current and future state of "sinusitis" complaints and "hanging touch" when the patient says they have sinusitis. You need to make them come in and get evaluated including imaging. I have had many such patients (some minor out of range Ig or immune parameter) over the years who had been treated by a immunologist south of UCLA and now "retired". Some patients came thinking they didn't need the IVIg and were easy to get off, those who were convinced it made the better (but insurance or other parties suggested stopping) were much more difficult.  Key is to set objective standards and following them.

What is the clinical significance of low plasmablasts potentially causing hypogammaglobulinemia, especially in regards to infectious complications and need for IgG replacement?
As these represent transiently circulating recently stimulated cells, I suppose it is simply a reflection of the low IgG responses and is a secondary event, not a primary "causal" one.

Good luck.

Andy Saxon,
UCLA

________________________________
From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Zachary D. Jacobs, MD
Sent: Tuesday, May 08, 2012 2:10 PM
To: 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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