[CIS PIDD] 8mo old boy hypereosinophilia

[Hoernes Miriam]

Yes we agree. Ellen Renner from Munich and her lab are doing the DOCK8 analysis and the STAT3 hotspots (as far as I have understood, these are the regions where 90% of the mutations are located).
Thank you very much,

Miriam Hoernes

Dr. med. Miriam Hoernes
Ärztin Abteilung Immunologie/Allergologie
Jeffrey Modell Diagnostic Center for Primary Immunodeficiencies
Universitäts-Kinderspital Zürich
Steinwiesstrasse 75
CH-8032 Zürich
Tel.: +41 (0)44-266-7311
Fax: +41 (0)44-266-7914
e-mail: miriam.hoernes at kispi.uzh.ch







-----Original Message-----
From: Bodo Grimbacher [mailto:bodo.grimbacher at uniklinik-freiburg.de] 
Sent: Tuesday, September 18, 2012 7:16 PM
To: pagid at list.clinimmsoc.org; 'pagid-bounces at list.clinimmsoc.org'
Cc: Hoernes Miriam; Seger, Reinhard
Subject: Re: [CIS PIDD] 8mo old boy hypereosinophilia

I think that Dock8 is more likely than STAT3.
Where and how do you do the analysis?
It is tricky for this 48 exon geneŠ

(One question: what are the STAT3 "hotspots"?)

Best, Bodo


****************************************
Univ.-Prof. Dr. med. B. Grimbacher

Scientific-Director
CCI - Centre of Chronic Immunodeficiency
UNIVERSITÄTSKLINIKUM FREIBURG
Tel.: 0761 270-77731  Fax: -77744
Engesserstraße 4, 79108 Freiburg
bodo.grimbacher at uniklinik-freiburg.de
www.uniklinik-freiburg.de/cci

and 

Consultant Immunologist
Department of Immunology
Royal Free Hospital
UNIVERSITY COLLEGE LONDON
Pond Street
London NW3 2QG
b.grimbacher at ucl.ac.uk
www.centreforimmunodeficiency.com









Am 18.09.12 15:56 schrieb "Reichenbach Janine" unter
<Janine.Reichenbach at kispi.uzh.ch>:


>Dear colleagues,

> 

>We would like to ask for your advice concerning a 7 months old boy, first

>child of non-consanguineous Swiss­Italian and Italian-South American

> parents, born at term with normal weight (3040g) and length (48cm).

> 

>The neonatal period was absolutely unremarkable, and then from 8 weeks

>onward severe, ongoing eczema with secondary total alopecia, and

> failure to thrive (no diarrhoea) was noted. At 5 months of age he

>developed fever and symptoms of upper respiratory tract infection with

>positive test for Picornavirus in nasal fluid (only 3 days of fever and

>no complications under symptomatic therapy). He

> had clinical and laboratory features of HLH without evidence for

>hemophagocytosis in bone marrow or blood, which resolved under low dose

>steroid treatment. Shortly after this episode a blood count showed

>excessive leukocytosis so that he was referred to our

> Division of Immunology/BMT for further investigation.

> 

>We noted massive eosinophilia and lymphocytosis, as well as elevated IgA

>and IgM in presence of normal IgG, the bone marrow-biopsy revealed

> no signs of malignancy, HLH or mastocytosis. The skin biopsy and LEKTI

>analysis excluded Netherton Syndrome, but evidenced massive T cell

>infiltrates in the skin. Histopathologists described the lesions as

>³juvenile xanthogranuloma². He had splenomegaly >

> hepatomegaly. Besides he is described to have recurrent urticarial skin

>lesions and recurrent swelling of the face.

>

> 

>Recently he has developed a central paresis of the facial nerve and

>multiple small cerebral infarctions (new ones and old ones) as well

> as a general cerebral atrophy, and lesions which could be suggestive of

>bleeding or vasculitis were noted on the MRI. The repeated bone marrow

>done for anaemia and thrombocytopenia showed progressive myelofibrosis.

>Oncologists have then treated him with high

> dose corticosteroid and Imatinib, resulting in reduction of the

>eosinophilia from 30G/l to 5G/l.

> 

>The lymphocyte phenotyping showed a marked lymphocytosis with elevation

>of all lymphocyte subsets and NK cells, normal CD4+25+/127- , perforin,

> CD40 and HLA class I and II expression. NK cell cytotoxicity test is

>pending. 

>PBMC show normal proliferation to stimulation with mitogens (PHA, Staph.

>Enterotoxin, Anti-CD3), but absent proliferation to stimulation

> with antigens (Candidin, Tetanus, CMV, PPD). Vaccination antibody titres

>for Tetanus and Pneumococcus are negative 2 weeks after the second

>immunization.

>

>The T cell receptor rearrangement was normal and there is no evidence for

>maternal T cells in the peripheral blood.

> 

>The total IgE was 412 kU/l and TH17 cells were low, the analysis of STAT3

>Hotspots and DOCK8 is ongoing.

>

> 

>Although local dermatologists do not think the alopecia is linked to EDA

>(he began to loose his hair, eyebrows and eyelashes by the age

> of 8 weeks, is able to sweat and his mother does not have signs of

>Incontinentia pigmenti), in the presence of unspecific eosinophil

>dermatitis, we are considering to study NEMO/IKBA, if DOCK8 and STAT3 are

>normal.

> 

>Any input concerning this puzzling patient would be greatly appreciated.

>Thank you very much in advance for your help and advice.

> 

>Please contact Dr. Miriam Hoernes (Miriam.hoernes at kispi.uzh.ch) who is

>not yet on the CIS-PIDD

> listservs for further information.

> 

>Best regards,

>Janine Reichenbach

> 

> 

>--------------------------------------------------------------------------

>----

>PD Dr. med. Janine Reichenbach

>Oberärztin Abteilung Immunologie/Hämatologie/KMT

>Jeffrey Modell Diagnostic and Research

>Center for Primary Immunodeficiencies

> 

>Universitäts-Kinderspital Zürich

>Steinwiesstrasse 75

>CH-8032 Zürich

>Tel.: +41 (0)44-266-7341

>Fax: +41 (0)44-266-7914

>e-mail:

>

>janine.reichenbach at kispi.uzh.ch

><BLOCKED::mailto:janine.reichenbach at kispi.uzh.ch>

> 

>

>

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