[PAGID] unusual SCIDs

[Kate Sullivan]

I'm voting for RAG1/2 mutations

Similar to the NEJM patients

Kate
On Oct 28, 2009, at 2:14 PM, <Aly.Mageed at devoschildrens.org> wrote:


> I would like to get the groups’ opinion regarding a 5 months old  

> white male who presented at 3 months with recurrent URIs and  

> eczematous rash. IgG was 62, IgA<8, IgM was 5, and IgE was 33.  WBC  

> was 15,000 with 16% lymphs and 44% Eos. Flow data: 2418 lymphs,  

> CD19= 1 cell, CD3 =1812 and CD16=585. Diagnosed as potential  

> Bruton’s and started on I g replacement and Btk genetic testing  

> (full-gene sequencing of all 19 exons with intron-exon boundaries  

> and UTRs) was performed and did not reveal any mutations and Btk  

> protein was also normal by intracellular flow cytometry on  

> monocytes. No transfusions and no sibs.

>

> Recent flow shows CD3= 5020, CD8= 2655 and CD4=1613 cells/uL with  

> 14.41% DNT cells.  ALPS screening (despite lack of classic ALPS  

> presentation) revealed only 0.5% of the DNT cells expressed the  

> alpha-beta TCR (were also B220 negative).  The remaining DNT cells  

> were negative for ab TCR, and may presumably be gd+ T cells.   

> Mitogen stim showed only 2% PHA, 40% PWM and 1% ConA relative to the  

> normal control.  TRECs were undetectable.  CD4 RTE (CD4+CD31+CD45RA 

> +) was 0.2% (only 3 cells/uL).  Next to zero naïve CD45RA+ T cells  

> and the majority of the CD4 T cells express CD45RO (~99%).  The CD8  

> RTE (CD8+CD103+CD62L+CD45RO-) showed an apparent increase due to the  

> overall CD8 lymphocytosis, however, again on examination of the  

> CD45RA gate, there were hardly any CD45RA+ CD8 T cells present, the  

> majority were CD45RO+ (>99%).  Therefore, in reality, CD8 RTE is  

> also absent.

>

> Now, he is in house with staph bactremia. Thriving at 8 Kg with some  

> diarrhea once started on Bactrim a month ago. Rash has its ups and  

> downs with increasing erythroderma and what looks like age/sunspots   

> that are increasing in #, which will be biopsied. Has mild  

> splenomegaly and some inguinal and cervical adenopathy. IgG is 522  

> (gets IG which will be increased) and IgE is 14, Eos = 13%. No  

> cytopenias. XX/XY probe surprisingly show all male XY cells with no  

> evidence of maternal engraftment.

>

> It is unclear as to how there can be such a substantial population  

> of T cells with a memory phenotype (CD45RO+) in the blood of this  

> infant along with a sizable population of DNT cells that are ab TCR- 

> negative, if there is no external source, such as maternal  

> engraftment, i.e. where are these cells originating from, especially  

> since thymic output appears to be non-existent.  There certainly  

> seems to be a reasonable amount of data in the literature to support  

> extrathymic maturation and TCR rearrangement in the human gut (both  

> gd and ab TCR+) but the question remains as to whether that is  

> indeed what is happening in this patient.  We are trying to look at  

> RAG1/2, Artemis and JAK3 but so far unsuccessful as he is Medicaid  

> and social worker is still working on these issues. HLA is pending  

> for UCB/MUD search. Is this Omenn’s ? Any further testing – would  

> gamma delta rearrangement analysis (clonality assessment), TCR V  

> beta analysis to look for oligoclonal populations be worthwhile?  

> Radiation sensitivity pathway? Additional thoughts??"

> Thanks

>

> Aly Mageed, MD, MBA

> Division Chief, Pediatric Blood & Marrow Transplant Program

> Director, Stem Cell Engineering Laboratory

> Helen DeVos Children's Hospital, Spectrum Health

> Associate Professor of Pediatrics, Michigan State University

> Grand Rapids, MI

> (616)-391-3962

> aly.mageed at spectrum-health.org

>

>


Kathleen Sullivan MD PhD
Professor of Pediatrics
Chief, Division of Allergy Immunology
The Children's Hospital of Philadelphia
(p) 215-590-1697
(f) 267-426-0363




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