[PAGID] CVID/HIGM/ALPS

[Lisa Kobrynski, MD, MPH]

Thank you for the comments:
Some answers to questions asked:
He does not have ectodermal dysplasia and has had normal numbers of NK cells by
flow on 3 occasions.
The flow from the LN originally showed a lot of plasma cells and more recently a
mix of T and B cells with the B cells predominantly expressing IgM on their cell
surface, but no light chain restriction.  He does not have granulomas in the
LN.
We considered myeloma, Bence jones proteins were not found in the urine and
there was no light chain restriction in the blood or LN.

He has a low proportion of CD27+ B cells, I do not see results on IgM or IgD
expression.  I will check with Cincinnati to see if it was done.  He does have a
high proportion of CD5+ B cells.  Previously he had a very low % of memory (RO)
T cells.

I looked at his Ig levels going back to 2002 - initially his IgA was elevated
also, but has declined to very low levels over the past years as his IgM has
increased markedly.  I do not see an IgE level. But he has never had any signs
of atopy or eosinophilia. 
Mel what were you thinking about?

Any other comments are much appreciated.
Thanks
Lisa





Quoting Jack Bleesing <Jack.Bleesing at cchmc.org>:


> Yes, HIGM6 is NEMO and 2 of my last 4 patients had no ectodermal

> dysplasia and/or its stigmata; one came originally for an ALPS

> evaluation (Evans' syndrome and LPD); the other was previously diagnosed

> with CVID.

> 

> Regards,

> 

> JB

> 

> 

> 

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

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

> 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/

> 

> 

> >>> "Renner, Eleonore  Dr." <Ellen.Renner at med.uni-muenchen.de> 8/7/2008

> 12:47:34 PM >>>

> Hi, 

> a hyper-IgM syndrome sound likely with decreased memory b cells, low

> IgG, normal to high IgM.

> Is there a ratio between IgM memory (CD19+, CD27+, IgM+, IgD+) and

> switched memory (CD19+, CD27+, IgM-, IgD-) to determined? Ratios of IgM

> memory : switched memory > 2:3 could be a hind.

> And the significant cervical lymphadenopathy could lead you to a AID

> mutation in my opinion. 

> HIGM6 is NEMO (correct?) and would fit IL12/INFg pathways infections

> observed? But any ectrodermal dysplasia or abnormal teeth? 

> Sincerely, 

> 

> Ellen

> 

> Dr. med. Ellen D Renner

> Kinderklinik und Kinderpoliklinik 

> im Dr. von Haunerschen Kinderspital

> Ludwig Maximilians Universität

> Lindwurmstr. 4

> D-80337 München

> Germany 

> 

> Phone:      **49-(0)89-5160-3157

>             **49-(0)89-5160-2811

> Fax:     	**49-(0)89-5160-7759 

> 

> Ellen.Renner at med.uni-muenchen.de 

> 

> 

>  

> 

> 

>  

> 

> -----Ursprüngliche Nachricht-----

> Von: pagid-bounces at list.clinimmsoc.org

> [mailto:pagid-bounces at list.clinimmsoc.org] Im Auftrag von Jack

> Bleesing

> Gesendet: Donnerstag, 7. August 2008 18:30

> An: pagid at list.clinimmsoc.org 

> Betreff: Re: [PAGID] CVID/HIGM/ALPS

> 

> HIGM6

> 

> Dr. Uzel at the NIH can sequence for you.

> 

> JB

> 

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

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

> 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/ 

> 

> 

> >>> "Lisa Kobrynski, MD, MPH" <lkobryn at emory.edu> 8/7/2008 10:45:55 AM

> 

> >>> >>>

> I was hoping to get some suggestions on a patient of mine I am

> following a 10 year old boy who presented initially with lymphadenitis

> and bronchiectasis at age 4 years.  He had malakoplakia found by the

> pathologists in his tonsillar tissue after a tonsillectomy.

> 

> He initially had low IgG and IgA with a normal IgM and very poor

> specific antibody responses and was given a diagnosis of CVID.

> Over the years he has had assorted infections (yersinia, salmonella

> enteritis,

> pneumonia) but developed very significant cervical lymphadenopathy last

> year. 

> Repeated biopsies have not shown any malignant transformation or

> clonality of the cells.  One node became necrotic and grew achromobacter

> xylosidans, which he has had intermittently in the blood ever since.  It

> is not resistant to everything.  Also his IgM is now over 3000.  ALPS

> panel initially showed an increase in DN T cells, activated T cells and

> a decrease in memory B cells.  DN T cell % had decreased at the last

> measurement.

> He has minimal hilar adenopathy, some mild inguinal adenopathy, but the

> cervical LN are the biggest issue.

> 

> I want to take a poll and find out who thinks this is just CVID with

> lymphoproliferation?  SHould we treat him with chemotherapeutic agents

> to suppress the lymphoproliferation?

> Could this have been ALPS all along?

> WHo thinks this is a HyperIgM - AID or UNG defect?  (We checked CD40

> and CD40L and they were normal)

> 

> Thanks

> Lisa

> 

> Lisa Kobrynski, MD, MPH

> Associate Professor of Pediatrics

> Division of Allergy and Immunology

> Emory University

> 404-727-3575

> 404-727-5045 (fax)

> 

> 



Lisa Kobrynski, MD, MPH
Assistant Professor of Pediatrics
Division of Allergy and Immunology
Emory University
404-727-3575
404-727-5045 (fax)