[PAGID] Autoimmune neutropenia

[Jack Bleesing]

Regarding the ALPS Panel run on this child, without going in to details; it does not fit ALPS and does not strike me as an ALPS-like study.

Folks have asked for details/refs about the ALPS panel: I don't think PAGID is the right platform to discuss (and as one can imagine) promote a specific lab or assay.  Those interested can contact me directly.

Regards,

JB

---------------------------------------------------------------------------
Jack J.H. Bleesing, M.D., Ph.D.
Cincinnati Children's Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Avenue, MLC 7015
Cincinnati, OH 45229
513-636-4266 (phone)
513-636-3549 (fax)
Jack.Bleesing at CCHMC.org
http://www.cincinnatichildrens.org/immunodeficiencies/


>>> Chris Seroogy <cmseroogy at pediatrics.wisc.edu> 07/16/08 10:36 AM >>>

Stephen,

I have not excluded WAS.  His platelet volume appears normal with excellent
counts.  Flow does not demonstrate low CD8 (in my experience a prominent
feature) and Treg numbers robust.  But, I agree remains a possibility.

Sorry I wasn't clear on the DNTCs.  This was run at Cincinnati and Jack can
correct me if I misstate.  For the ALPS panel, he has 2/4 criteria:

1. Absolute DNTCs 127 (reference range 6-33) of these 24.7% are B220+DNTCs
2. CD27+ B cells are low at 6% (reference range 15-52)

Interpretation, abnormal study but not clearly suggestive of ALPS.

Chris



On 7/16/08 9:22 AM, "Stephan Ehl" <stephan.ehl at uniklinik-freiburg.de> wrote:


> Chris,

> 

> have you excluded WAS?

> what do you mean by ALPS panel normal but 22% DNT cells?

> 

> Ashish,

> 

> do you have fibroblast from your patient? We could do a VDJ

> recombination assay in these cells to investigate the significance of

> the RAG mutation in your patient.

> 

> Best wishes,

> 

> Stephan

> 

> Ashish Kumar schrieb:

>> Chris,

>> 

>> You described a typical case of autoimmune neutropenia.  AIN can last

>> a long time and I don't think G-CSF is doing much other than making us

>> feel better when we temporarily fix his neutropenia. You could give

>> him all the G-CSF you want, but as soon as you stop it, his

>> neutropenia will recur. The bone marrow findings are also typical of

>> AIN. I have a hard time chalking the sepsis/osteomyelitis to AIN, and

>> it may be the other way around. MRSA osteomyelitis can occur with a

>> normal neutrophil count too.

>> 

>> I have a patient who had sever AD and FTT, who had eosiniphilia, high

>> IgE, and initially also had lymphocytosis - ALC of 24k, mostly

>> T-cells. He too had normal FOXP3 expression with relatively high

>> number of CD25+/FOXP3+ cells and every other immune testing was

>> negative as well. I found him to have a heterozygous RAG-2 mutation,

>> one that hasn't been described before. No one knows if this was a red

>> herring or not, but my patient is also African-American with a strong

>> family history of atopic dermatitis. He also tested positive for all

>> food allergies. I tried several topical steroid preparations for his

>> skin, none worked and he had chronic watery diarrhea that kept him

>> from gaining weight. At 10 months, he weighed 4.5 Kg. Systemic

>> steroids made him a new kid in 1 week. When I tapered the steroids,

>> his skin and diarrhea flared again, so I have initiated a very slow

>> wean. He has finally gained some weight. I now ignore the food allergy

>> tests in these patients and rely on challenge which typically allows

>> resumption of a normal diet.

>> 

>> Ashish

>> 

>> Ashish Kumar, MD, PhD

>> Assistant Professor of Pediatrics

>> Division of Hematology/Oncology/Blood and Marrow Transplantation

>> University of Minnesota

>> 

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>> 

>> Chris Seroogy wrote:

>>> Dear Colleagues,

>>> 

>>> I would appreciate any thoughts on an enigmatic 10m/o African

>>> American boy

>>> followed at our institution for multiple medical problems.  He was

>>> born term

>>> and well except for mild atopic dermatitis until Jan. of this year.

>>> At that

>>> time he presented with MRSA sepsis/osteomyelitis (hip) and

>>> neutropenia.  His

>>> bone marrow showed increased myeloid precursors and trilineage

>>> hematopoiesis.  Extensive immune evaluation negative.  The

>>> neutropenia was

>>> felt to be secondary to his infection felt to be caused by breakdown

>>> of his

>>> integument.  However, the neutropenia has persisted to the point that

>>> our ID

>>> folks started GCSF.  I was consulted some months later to revisit his

>>> immune

>>> system since he had and influenza A infection and history of

>>> recurrent URTI.

>>> There is a strong family history of atopic and this child has severe

>>> AD and

>>> probable clinical food allergy with FTT thought to be secondary to poor

>>> intake.  We have optimized his diet and he is making slow, but steady

>>> gains

>>> in his weight.  Development is not a concern.

>>> Notable data:

>>> 

>>> Repeat flow, antibody levels and titers, CH50, HIV all negative/normal.

>>> IgE 2000 with multiple food sensitivities

>>> Foxp3 detactable and high percentage in CD25+

>>> ALPS panel not indicative of ALPS, but high % B22-+DNTC (24.7%)

>>> Antineutrophil antibodies strongly positive (>3SD and run at ARUP)

>>> 

>>> No enlarged liver or spleen.  We held his GCSF and repeated

>>> marrow--it was

>>> difficult to interpret even 4 days off GCSF with a tremendous number of

>>> hematogones, trilinear hematopoiesis and mostly mature granulocytes

>>> in the

>>> granulocytic lineage.

>>> 

>>> We tried high-dose IVIG thinking that might give a respite from GCSF and

>>> this was without success.  His neutrophils have been consistently

>>> below 500

>>> while holding GCSF now.  He is being admitted for fever with an ANC 180.

>>> 

>>> My question is if this is a phenotype that others have seen?  Any

>>> recommended additional testing or therapeutic interventions?  Thank

>>> you for

>>> your opinions, Chris

>>> 

>>> 

>>> Chris Seroogy, M.D.

>>> 

>>> University of Wisconsin

>>> 

>>> Assistant Professor

>>> 

>>> Dept. of Pediatrics

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