[PAGID] VOD/CID - Sp110

[Jack Bleesing]

Abnormal to absent NK-cell function.

T-cell function CID to SCID range (yes/no steroids).

B-cell phenotyping: reduced to near-absent memory B-cells. Serology:
normal to decent protein responses; hit or miss responses to prior viral
infections, including those against viral agents found in liver or
elsewhere.

JB


>>> Stephan Ehl <stephan.ehl at uniklinik-freiburg.de> 9/26/2008 10:02 AM

>>>

Dear Jack,

the CID/HLH/XLP sun has not yet completely risen, so genetic testing is

of limited value. What do the functional assays say?

St.

Jack Bleesing schrieb:

> Good morning Folks:

>

> I was wondering if there is anybody, who would like speculate whether

[mono-allelic] Sp110 mutations have a clinical phenotype.

>

> The reason I am asking is that every couple of months or so, we see a

child (male and  - seemingly healthy - present with severe
hepatitis/cholangitis that is cellular based (no autoantibodies and no
response to "low" dose steroids). When we get involved and look at the
immune system (sometimes before steroids are started, as the Liver Team
is starting to see a pattern as well), it looks like a SCID/CID immune
system. Multi-gene workup of everything under the CID/HLH/XLP Sun, has
not shown any defect. 

>

> The cellular mechanism in the liver appears to suggest a HLH-like

process (with increased sIL-2Ra and ferritin) with cytotoxic T-cells,
akin EBV-driven HLH. In the liver, we sometimes, not always, find some
virus (HHV-6, entervirus, adenovirus found so far), suggesting that a
viral infection provided the trigger. When we initiate HLH therapy,
things improve relatively quickly. Cytopenias, especially involving
platelets and neutrophils are invariably present, sometimes with
hemophagocytosis in the bone marrow. Coagulapathy (not due to synthetic
dysfunction) also.

>

> Sp110 hasn't been looked at. 

>

> Regards,

>

> Jack

>

>

---------------------------------------------------------------------------

> Jack J.H. Bleesing, M.D., Ph.D.

> Associate Professor of Pediatrics

> 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/ 

>

>

>

>   


-- 
Prof. Dr. Stephan Ehl
Immunologie/Rheumatologie

UNIVERSITAETSKLINIKUM FREIBURG
Zentrum für Kinderheilkunde und Jugendmedizin
Mathildenstrasse 1, 
79106 Freiburg

Tel +49 761 270-4309 (4301) / Fax -4599
stephan.ehl at uniklinik-freiburg.de 
http://www.uniklinik-freiburg.de/kinderklinik/live/forschung/immunologie.html