[PAGID] Immunodeficiency patient

[Renner, Eleonore PD Dr.med.]

Hi,
Is there eosinophilia? Sounds similiar to several patients with DOCK8 mutations we saw including this mild T cell deficiency in-vitro and for sure clinical ... or also perhaps possible OMENN? But IgE is normal, so this is just a guess. If it is confirmed AR-HIES we would recommend BMT currently.
Kind regards from Munich, 
Ellen Renner 
________________________________________
Von: pagid-bounces at list.clinimmsoc.org [pagid-bounces at list.clinimmsoc.org] im Auftrag von Cowan, Mort [mcowan at peds.ucsf.edu]
Gesendet: Donnerstag, 16. September 2010 20:39
An: pagid at list.clinimmsoc.org
Cc: Gilman, Andrew L
Betreff: [PAGID] FW: Immunodeficiency patient

Dear colleagues,

I’d like your thoughts regarding a patient with PID who is being considered for a BMT by Dr. Andy Gilman (see below).

Morton J. Cowan, M.D.
Professor of Pediatrics
Chief, Blood and Marrow Transplant Division
UCSF Children's Hospital, Room M659
505 Parnassus Ave
San Francisco, CA 94143-1278

Phone: 415-476-2188
FAX: 415-502-4867

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I would appreciate your opinion on whether or not you would transplant this patient without a phenotypic or molecular diagnosis.

The patient is a 2 ½ year old whose main problems are severe lymphopenia, wheezing, eczema, and chronic autoimmune hemolytic anemia requiring steroid therapy.

He was in good health until February, 2009 when at 11 months of age he was hospitalized for reactive airway disease and possible pneumonia.

April, 2009: Otitis media and reactive airway disease treated with prednisone and Pulmicort.

May, 2009: Hospitalized for extensive varicella following a varicella vaccination (DFA positive lesion and very high viral load in blood) and treated with intravenous acyclovir with resolution.  His WBC, platelets, and neutrophil count were normal. However, he had severe lymphopenia (ALC = 400). On retrospect, this was present in February, 2009. He also had anemia with a hemoglobin of 9.9. In retrospect, he had more severe anemia with a hemoglobin of 8.6 in February. His IgG was 1013, IgA 8 and IgM 189. Lymphocyte subsets showed the following absolute counts: CD3 137 (37%), CD4 81, CD8 52, CD19 170 (46%) and CD16/56 59 (16%). HIV antibody negative. Positive IgG and IgM for varicella. ADA and PNP were normal prior to any transfusions.

June 2009: Viral illness (parainfluenza type II) followed by autoimmune hemolytic anemia with positive Coombs and warm and cold autoantibody on 07/03/09. He was treated with IVIG with excellent response. Lymphocyte subsets on 06/30/09 showed CD3 187 (55%), CD4 64 (21%), CD8 95 (32%), CD19 51 (13%), CD16/56 115 (30%). In addition, he had CD45RO 66 (16%) and CD45RA 8 (2%). PHA (unknown but likely the highest concentration) was 54,829 (ref 62,688-286,636) He had had oral steroids recently.  HIV Ab and PCR negative.   A CT of chest in Oct 2009 was unremarkable except for mild bronchial wall thickening in perihilar region and mild diffuse prominence of interstitium.

Dec 2009: He had a recurrence of autoimmune hemolytic anemia with a positive Coombs. He was treated with steroids this time.
His steroids were slowly weaned off, but his anemia recurred when they were stopped (despite being given monthly IVIG starting in March 2010).

3/19/2010
TRECS (Viracor) Result <74 (normal >801)

June 2010: He had an open lung biopsy that was read as chronic aspiration but the pulmonologist doesn’t believe it and is going to send it off for second opinion. Although GER could explain some wheezing, he has persistent significant wheezing. The pulmonologist says that it only improves with high dose steroids and that he has SOB when steroid dose is lowered.

Here are other Immune studies with dates:

12/15/09 lymphocyte proliferation (Duke)
PHA Result = 32,102 (normal 62,688-286,636)
 5/30/10 (Duke)
PHA result = 25,314

12/15/09 Lymphocyte Enumeration
CD45RA,CD3+ Result = 19.5% (normal 20.3-44.1)
CD45RO,CD3+ Result = 34.2% (normal 30.4-51.3)
The percentages were equal when repeated in 5/30/2010 (28.5%)

The patient does have immunoglobulins and appears to have a specific antibody response.
1/21/10 – NO IVIG in previous 6 months
Diptheria Ab = <.10
Tetanus Ab = 0.21
HIB Ab = 0.21
IgG 1272
IgA 45
IgM 248
IgE 4.95
S. Pneumo 3 of 14 serotypes >1.30 (Types 14, 26, 57)
Isohemaglutinin A = 128
Isohemaglutinin B = 32

He did not have any problems with MMR vaccination.

Genetic testing negative for Di George


>From Cincinnati Children’s lab 4/29/10:


CD127+ 70%
CD127+3+ 80%
CD127+4+ 91%
CD127+8+ 67%
CD127+16/56++ 47%

CD132+ were all 99-100%

CD40L and ICOS expression normal

FISH neg for XX cells

Clinically, he is well except for his persistent episodes of wheezing and his AIHA which is controlled with relatively high dose of steroids. He still has a high retic and positive Coombs. He has not been given Rituxan. His growth is poor due to chronic steroids. His last ALC was 400.

We sent IL-2Rg and IL-7Ra gene testing to Correlagen. They are normal so far but testing is not complete yet. Jennifer Puck said that his STAT5 phosphorylation was normal so this rules out IL-2Rg and JAK3 mutations.

Thank you for your thoughts!

Andy

Andrew Gilman, MD
Director, Pediatric Blood and Marrow Transplantation
Levine Children's Hospital
Carolinas Medical Center
PO Box 32861
Charlotte, NC 28232-2861
Ph: (704) 381-6847
Fax: (704) 381-6841
Cell: (704) 615-2744

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