[CIS PIDD] [cis-pidd] obesity, fever, elevated B cells

CIS-PIDD cis-pidd at lists.clinimmsoc.org
Tue Jan 31 16:05:22 EST 2017 

Hi Sergio and Leonardo,
Thanks for your suggestions! He reportedly had EBV several years before the visit and resolved. I will check for EBV titers / virus when I see him next. MAGT1 sequence was negative. NLRP12 sequence was negative.
Regards,
Jordan
From: CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Reply-To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Date: Tuesday, January 31, 2017 at 12:23 PM
To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Subject: Re: [cis-pidd] obesity, fever, elevated B cells

Hi Jordan,
What about EBV status? MAGT1 pts can have elevated B cells.
Sergio

Sergio D. Rosenzweig, MD, PhD
Immunology Service, DLM, CC, NIH
10 Center Dr., Bldg. 10, DLM, CC 2C-410F
Bethesda, MD 20892
srosenzweig at cc.nih.gov<mailto:srosenzweig at cc.nih.gov>

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From: CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Reply-To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Date: Tuesday, January 31, 2017 at 11:29 AM
To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Subject: Re: [cis-pidd] obesity, fever, elevated B cells

Hi Jordan,
I would agree with Mikko that Patient one should be assayed for the alpha tryptase CNV. We are working with a commercial lab that you can just send it off to, but for now we could take a look. We’ve seen inflammatory symptoms in a small subset of the alpha hypertryptasemia patients, including fevers and aphthous ulcers, occasional colitis, etc. The tryptase level is right in line with what we see in those with duplications, and you already have the normal marrow to rule out most myeloid issues (for now). That said, given how infrequently we see the inflammatory phenotypes and that fact that indeed I’d be concerned about the B-cells as well, and it could be possible that two things are going on.

j

From: CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Reply-To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Date: Tuesday, January 31, 2017 at 11:16 AM
To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Subject: Re: [cis-pidd] obesity, fever, elevated B cells

Dear Mikko,
Thanks for these helpful suggestions. I hadn’t considered alphatryptasemia for patient 1. I will contact Josh Milner. Still, the B cells and fever seem outside of range of phenotypes. I will look more deeply into the B cell compartment and look for monoclonal Ig, as well. I didn’t mention it, CARD11 sequence was normal in patient 1. Not done in patient 2. If anything interesting comes up, I will let you know.
Regards,
Jordan
Jordan Abbott, M.D.
Assistant Professor of Pediatrics
National Jewish Health
1400 Jackson St., J333
Denver, CO 80206




From: CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Reply-To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Date: Monday, January 30, 2017 at 11:08 PM
To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Subject: Re: [cis-pidd] obesity, fever, elevated B cells

Hi Jordan,

the level you describe for CRP is very typical for obese individuals in general. However, the extent of CRP elevation in either does not suggest AIS/AID to me.

Patient 1 seems to have no clonal mastocytosis but has clearly elevated tryptase, did you consider alphatryptasemia in his case, symptoms to suggest it? What was the extent of fever: subfebrile/ true fever? Discuss his case with Josh Milner and Jonathan Lyons, if suggestive symptoms?

I am not aware of B lymphocytosis associated with obesity. Smoking (do these smoke?) would be associated?? Persistent polyclonal B cell lymphocytosis? IgM increased? Large (?) spleen could suggest this? B cells sometimes binucleated, associated with HLA DRB1*07. Dyspnoea? Diffusion?

B lymphocytosis is of course linked to some ALPS-related disorders like BENTA/CARD11, which I guess may have rather indolent courses even up to adult age, but you do not list anything to suggest this? I am sure you considered this already, but if necessary: see Buchbinder and Outinen articles for extension of phenotype. Memory B cells? Polyclonal?

Yours, hope these help

Mikko

Mikko Seppänen, MD, PhD

Head, Rare Disease Center,
Helsinki University Hospital (HUH)
FINLAND

phone +358 947180201
GSM +358 50 4279606
fax +358 9 47174703



Oyl Mikko Seppänen
Harvinaissairauksien yksikkö (HAKE)
[X]

Head, Rare Disease Center,
Helsinki University Hospital (HUH)
FINLAND

phone +358 947180201
GSM +358 50 4279606
fax +358 9 47174703
CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> kirjoitti 30.1.2017 kello 22.42:

Hello all,



Wondering if you have any thoughts on a couple of patients I have seen this past year. Both are obese pediatric patients with chronic fever and elevated B cells.



Patient 1 is a now 17 year old male. BMI from high 30s to 48kg/m^2 most recently. He complains of chronic fever without clear pattern and daily vomiting. Previously, he had abdominal pain and a lower endoscopy that showed mast cells in the lamina propria. Tryptase was 15.4 mcg/L, bone marrow was unremarkable without cKIT mutation. Spleen was removed  (not my recommendation) and was normal. Since I started seeing him, he has had chronically elevated CRP 3 to 6 mg/dl, CD19 count around 1000/ul (500 is upper limit), and borderline elevated CD3+4+ count. Cytokine panel (IL2, sCD25, IL-12, ifng, IL4, IL5, IL10, IL13, IL1b, IL6, IL8, TNFa, IL17) all normal. IL18 level was not elevated. Sequencing 25 fever genes panels found no suspicious variant. 1 week trial of anakinra reduced the CRP to normal but did not improve symptoms. No rash or joint symptoms. No other concerning symptoms.



Patient 2 is a 13 yo male. BMI is 44. Chronic fever onset around grade school age. Temps up to 102F once monthly but no clear pattern. Elevated temps otherwise throughout the month but lower. CRP with minor elevation to 0.5 to 1.5 mg/dl. Lymphocyte phenotype was normal except for B cells elevated to 1000/ul.  Cytokine panel (IL2, sCD25, IL-12, ifng, IL4, IL5, IL10, IL13, IL1b, IL6, IL8, TNFa, IL17) all normal. Sequencing 25 fever genes panels found only a heterozygous MVK variant, V377I. IgD level in the blood was normal. We are awaiting urine organic acids during a fever episode, but I am doubtful that MVK deficiency is the cause. He lacks associated symptoms other than malaise with the fevers.



Has anybody else seen similar patients? Is there a connection between the obesity, fever, and elevated B cell numbers that I am missing?



Thanks,

Jordan

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