[PAGID] VOD/CID - Sp110

[Jack Bleesing]

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

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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/