[CIS PIDD] [cis-pidd] 2yo with hemolytic anemia and T/B abnormalities

[Verbsky, James]

I concur with Drs Berger and Vasconcelos..if there is an IL-2 production defect this will overcome it.  However..if it's a mutation in CD25 or gammaC IL-2 wont work (unless you use very high doses for CD25)...IL-15 does so you could try that(at least for CD25).  We do mitogens with the other gamma common chain family members (2, 7, 15) .  You could also look at phospho-Stat5 as a functional readout.


One other thought...(which doesn't explain the mitogen problem)...I don't know of many PIDs that present with low CD4 cells (other than the mentioned Class II or Lck), but  xIAP deficiency appears to have low CD4/CD8 ratios..at least in the initial publication (4 of 7 patients, our xIAP was similar).  Again..mitogens should be normal particularly if the cells were viable..just curious if others have thoughts about the 4/8 ratio.

James

-----Original Message-----
From: Mel.Berger at cslbehring.com [mailto:Mel.Berger at cslbehring.com] 
Sent: Tuesday, December 11, 2012 12:04 PM
To: CIS-PIDD
Subject: RE:[cis-pidd] 2yo with hemolytic anemia and T/B abnormalities

You can try adding IL-2 to standard mitogen assys.



Mel Berger

________________________________
From: Cooper, Megan [Cooper_M at kids.wustl.edu]
Sent: Tuesday, December 11, 2012 12:33 PM
To: CIS-PIDD
Subject: RE:[cis-pidd] 2yo with hemolytic anemia and T/B abnormalities

Hi James - He has some diarrhea (although started when he initiated PCN prophylaxis), 80th % ht/wt, has very mild eczema.  He has CD25 by flow, but we could sequence for a functional defect, good thought.  T cell activation does seem to be his most profound defect.

Thanks - Megan

From: Verbsky, James [mailto:jverbsky at mcw.edu]
Sent: Tuesday, December 11, 2012 11:25 AM
To: CIS-PIDD
Subject: RE:[cis-pidd] 2yo with hemolytic anemia and T/B abnormalities

Megan

Any enteropathy, eczema??  CD25 deficiency will give you AIHA and poor lymphocyte mitogenic responses..usually have IBD...but it could still be early in a 2yo.  Id also consider STAT5b..is he well grown?

Best

James

From: Cooper, Megan [mailto:Cooper_M at kids.wustl.edu]
Sent: Tuesday, December 11, 2012 11:18 AM
To: CIS-PIDD
Subject: [cis-pidd] 2yo with hemolytic anemia and T/B abnormalities

Hi Everyone,

I saw an interesting patient as a consult from our Heme/Onc doctors and was wondering if anyone had thoughts about a potential diagnosis.  This is a 3yo who had refractory hemolytic anemia at age 2 yo (unknown cause after extensive testing, possibly autoimmune) with subsequent pancytopenia thought to be d/t splenic congestion.  His cytopenias and anemia resolved with splenectomy.  He has had recurrent upper respiratory infections and an immune work-up is significant for low CD4 count with an activated/memory phenotype and very poor proliferation (0 to candida and tetanus; low with mitogens); elevated B cells but very low % class switched; normal total immunoglobulins with non-protective tetanus titer (did respond to vaccine) and strep pneumo titers (did not respond to prevnar).

He has not had any serious infections, is well grown and developing normally.

Testing so far has included a negative ALPS screen, positive expression of CD40/CD40L, normal PNP.  Pending is AID and UNG sequencing, and I'll probably send Rag/artemis for hypomorphic mutations as well (although he doesn't really fit except for activated/possibly oligoclonal T cells).  Some specific labs are below.

Any thoughts are appreciated.  I'm also wondering if some of his immunologic abnormalities might be due to splenectomy - I'm doubtful of this but don't have a lot of experience testing kids after splenectomy.

Thanks,

Megan

Megan A. Cooper, MD, PhD
Assistant Professor, Department of Pediatrics Division of Rheumatology Washington University School of Medicine Cooper_m at kids.wustl.edu<mailto:Cooper_m at kids.wustl.edu>
Lab website: http://research.peds.wustl.edu/Default.aspx?alias=research.peds.wustl.edu/Labs/Cooper_M
(lab office) 314-286-0262
(Rheum office) 314-454-6124
(lab fax) 314-286-2895
(Rheum fax) 314-454-4861

Specific labs:
IgG 409; M 86; A 19; E 7.9

CD4 - 558 cells/ul (HIV negative)
CD8 - 1766
CD19 - 5020
CD56/16 - 1394
Class I - present on all
HLA-DR - present on all B cells
CD40  + on all B cells
CD40L - 2% CD4s resting; 44% CD4s activated (ref 79-96%)

CVID flow panel:
T cells - CD4RA 27%; CD4 RO 64%; HLA DR CD4 2%; HLADR CD8 11% B cells - CD21+CD27- 64%; CD21-CD27+ 0%; CD21+CD27+1%; IgD+CD27- 92%

DNT screen - 0.3% DNTs
Other T cell phenotyping with DNT screen: CD3+CD25+ count 157 (low, ref 273-599); CD3+HLADR+ 1804 (high - ref 51-246)

Proliferation - very poor to PWM, PHA, candida, & tetanus (before re-vaccination).  His Candida and Tetanus proliferation was actually 0% (flow assay) with decent cell viability and some proliferation to mitogens



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