[CIS PIDD] [MARKETING][cis-pidd] CMV, CD4 lymphopenia, adenopathy, nephritis....

Thu Jun 11 13:44:30 EDT 2015

Thanks Beata for the suggestion!  No skeletal changes.

Dave

>>> wolska <bwolska at interia.pl> 6/11/2015 5:47 AM >>>

Hi
Did you think about Schimke syndrome? 
Has your patient got any skeletal abnormalities ?

-- 
Beata Wolska - Kuśnierz
Oddział Immunologii
IP-CZD 
Al.Dzieci Polskich 20
04-730 Warszawa
tel. 22 815 73 85
fax. 22 815 73 82
bwolska at interia.pl

Od: "Seppänen Mikko" <Mikko.Seppanen at hus.fi>
Do: "CIS-PIDD" <cis-pidd at lyris.dundee.net>; 
Wysłane: 8:00 Środa 2015-06-10
Temat: VS: [MARKETING][cis-pidd] CMV, CD4 lymphopenia, adenopathy,
nephritis....

Hi David, 
at “this advanced” age, whenever there is B- and NK-penia (+/- CD4
penia) I would rule out GATA2 first. First sequencing and then - if no
mutations found - GATA2 mRNA level check to rule out GATA2
haploinsufficiency.
In our material, monocytopenia and even DC-penia often seem to occur
later in the disease than B- and NK-penias, and in rough testing NK
function seems in it to be rather normal (but low counts of course).
Check these as well of course, but do not rule out GATA2 if still
normal.
Mass lesions with EBV positivity as well as disseminated CMV have been
reported in GATA2, thus this mass-lesion might be compatible with GATA2?

Though the interstitial nephritis sounds like it could have been
provoked by e.g. NSAIDs for fever, experimentally low GATA2 mRNA has
been linked with glomerulonephritis. Swelling: lower limbs (Emberger?)?
At least in Finland, though we in control WESes (n >3200) do not seem
to have an excess of any pathogenic GATA2 mutations, GATA2 def seems to
be the second most common later-onset PIDD after CVID. Thus I would next
think of other options only after GATA2 has been definitely ruled out. 
That being said, there are of course a number of other PIDD gene
mutations possible, but those I would then pursue with clinical WES, and
if the insurance company disagrees, “they sure do not understand simple
math” ( ;=O  :=) )
ATB
Mikko

oyl Mikko Seppänen
Harvinaissairauksien yksikkö (HAKE), HUS

Mikko Seppänen, MD, PhD, Associate professor 
Specialist in Internal Medicine and Infectious Diseases
Chief, Rare Disease Center, Helsinki University Hospital (HUH)
Children’s Hospital, P.O.Box 280
FI-00029 HUS
FINLAND
&
Senior Consultant (PIDD)
Adult Immunodeficiency Unit
Inflammation Center, HUH

phone +358 9 47180201
GSM +358 50 4279606
fax +359 9 47174703

Lähettäjä: David Buchbinder [mailto:dbuchbinder at CHOC.ORG] 
Lähetetty: 10. kesäkuuta 2015 8:19
Vastaanottaja: CIS-PIDD
Aihe: [MARKETING][cis-pidd] CMV, CD4 lymphopenia, adenopathy,
nephritis....

Dear Colleagues,

I wanted to see if anybody has any suggestions with respect to the case
below with respect to additional diagnostic work up or suggestions for
targeted sequencing for some of the more novel immune dysregulation
syndromes (e.g. PI3KCD, etc.).  

We have a 7 year old previously healthy male who originally presented
with abdominal pain and pancreatitis. 

Imaging documented a lung nodule retroperitoneal mass as well as
diffuse mesenteric  and retroperitoneal adenopathy.

Pathologic examination documented CMV inclusions on the lung biopsy and
retroperitoneal mass.  He was treated with ganciclovir.  There was a
lymphocytic infiltrate present (largely T cells) and some eosinophils. 
No IgG4 plasma cells were noted.   He developed chylous ascites and
chylothorax which resolved.

Most recently he came in with fevers, night sweats, and swelling.   Due
to concerns of renal insufficiency a biopsy was obtained.  It
demonstrated acute tubulo-interstital nephritis.  The intersitium
demonstrate lots of lymphocytes, macrophages, eosinophils, and few
plasma cells.  Immunostains for CMV (and EBV) were negative.  We also
biopsied the mesenteric / retroperitoneal adenopathy.  There was
lymphohistiocytic infiltrate (largely T cells and histiocytes).  No
malignancy. 

His immunoglobulin levels are relatively unremarkable - IgE 229, IgA
132, IgG 1164, IgM 38 although his IgM is a bit low. 
His lymphocyte panel demonstrates a slightly reduced number of B cells
146 / uL and NK cells 56 / uL.  His CD3 and CD8 numbers are fine.  
His CD4 numbers are low at 180 / uL.  Naïve CD4 and  CD8 percentages
are low  (8.1% and 23% respectively).    CD4 cells have slightly
decreased expression of TCR alpha/beta (80%).
Mitogens were generally normal with some decreased Ag specific
responses.  
NK cytotoxicity was normal.  
Some limited genetic analysis (e.g. NGS SCID panel) was done and
negative. 

Thanks as always....

Dave Buchbinder
CHOC Children's - UC Irvine

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