[CIS PIDD] [cis-pidd] Asking for advice in AIHA-combined immunodeficiency

Fri Aug 8 05:43:19 EDT 2014

Dear Dr. Gonzalez, 

I agree with Gigi. 
the expansion of transitional B cells is a more common phenomenon in combined immunodeficiencies. 
CARD11 has no Tregs. this will give you another clue. additionally IkBa degradation after BCR stimulation is completely absent, if you perform this assay. 
The other clue in regard to CD21low vs transitional B cells if you have not stained for CD38 is the expression of CD19 which is always elevated on CD21low B cells compared to the other B cells. 
I hope this helps, happy to have a look at the FACS plots 

greetings

klaus 

Prof. Dr. med. Klaus Warnatz

UNIVERSITÄTSKLINIKUM FREIBURG
University Medical Center Freiburg
Center for Chronic Immunodeficiency
Division of Rheumatology and Clinical Immunology

Tel: +49-761-270-77640 / FAX -71000 / Pager: 12-7100

Breisacher Str. 117, 79106 Freiburg, Germany
klaus.warnatz at uniklinik-freiburg.de
http://www.uniklinik-freiburg.de/cci

Am 08.08.2014 um 09:25 schrieb Nacho Gonzalez:

> Dear Dr. Prockop and Notarangelo,
> 
> Thanks for your kind replies.
> The lymph subsets and proliferation tests were performed 6 months ago.
> At that time the patient was taking PRD 7.5mg qd (0.11mg/kg). So no
> influence in the results is expected.
> CARD11 is a good point. We´ll look for transitional B cells. Thank you
> for clarifying
> 
> Best wishes,
> 
> Luis Ignacio Gonzalez-Granado
> Immunodeficiencies Unit.
> Pediatrics
> Hospital 12 octubre
> Madrid. Spain
> 
> 2014-08-08 1:56 GMT+02:00 Notarangelo, Luigi
> <Luigi.Notarangelo at childrens.harvard.edu>:
>> Dear Dr Gonzalez,
>> 
>> This is likely a co bi ed immunodeficiency. You mentioned markedly increased proportion of CD19+ CD21lo, and perhaps you were thinking that this could represent autoimmune prone B cells. However, use of CD21 alone is not sufficient. It would be important to look also at CD38. These could be transitional B cells (CD19+ CD21lo CD38+) as opposed to the autoimmune prone CD19+ CD21lo CD38lo. A marked increase of transitional B cells associated with severe CD4 lymphopenia might indicate CARD11 mutations.
>> With regard to treatment, I would not be too worried about rituximab, but MMF is also a possibility, as suggested by Dr Prockop
>> 
>> Best regards
>> 
>> Luigi D Notarangelo
>> 
>> Sent from my iPad
>> 
>> Luigi D. Notarangelo, MD
>> Jeffrey Modell Chair of Pediatric Immunology Research
>> Division of Immunology, Boston Children's Hospital
>> Professor of Pediatrics and Pathology, Harvard Medical School
>> Karp Research Building, Room 10217
>> 1, Blackfan Circle
>> Boston, MA 02115
>> USA
>> 
>> Tel: 617-919-2277
>> FAX: 617-730-0709
>> 
>>> On Aug 7, 2014, at 7:34 PM, "prockops at MSKCC.ORG" <prockops at MSKCC.ORG> wrote:
>>> 
>>> Dr Gonzalez
>>> 
>>> I am not clear from you note if the immune phenotype and function was
>>> performed while on low or high dose steroids?
>>> 
>>> We have recently been able to successfully avoid rituximab in a
>>> patient with post-transplant AIHA with MMF. There is a small/limited
>>> literature on this approach in adults and canines....
>>> 
>>> Best,
>>> Susan Prockop
>>> 
>>> Assistant Attending
>>> Pediatric BMT Service
>>> Memorial Sloan-Kettering Cancer Center
>>> prockops at mskcc.org
>>> 212-639-6715
>>> 
>>> 
>>> 
>>> -----Original Message-----
>>> From: Nacho Gonzalez [mailto:nachgonzalez at gmail.com]
>>> Sent: Thursday, August 07, 2014 4:13 AM
>>> To: CIS-PIDD
>>> Subject: [cis-pidd] Asking for advice in AIHA-combined immunodeficiency
>>> 
>>> Dear all,
>>> 
>>> this is an update for the patient posted on Aug 15, 2012  [14y.o Chinese boy with autoimmune haemolytic anemia and profound CD4 lymphopenia].
>>> 
>>> Despite 2 years free of infections and stable disease under steroid maintenance treatment (prednisone 5-10 mg qd) he has had a new hemolytic crisis with increased reticulocyte count for the last 2 weeks (290.3 x1000/µl,  10,5%). Bili 2 - 3.7 mg/dL.  Hb (in june, 12.3 g/dL  now 10.2 g/dL).
>>> 
>>> Steroids have been increased up to 15 mg qd last week. He has never received Rituximab. I am concerned about its use in this patient (total lymph 737/uL (CD3+ 378, gd 19%, CD4+ 94 /uL , CD8+ 186/uL,
>>> CD19+ 284/uL, CD56+/CD3- 62/uL.  %Lymph T CD4+CCR7+CD45RA+  3.2% [N >
>>> 25%].  %Lymph T CD8+CCR7+CD45RA+  12%  [N > 28%].  %CD4+CD45RA+CD31+ 3% [N> 26%]. Normal B-cell compartment except for  %CD19+CD21Low 60% [N < 9%]. Proliferation tests: anti-CD3 5024 cpm [N > 9000], CD3 +
>>> CD28 2016 cpm [N > 80000] PHA 16428 cpm [N > 50000] IonoPMA 69372 cpm [N > 60000].
>>> Calcium flux assesment is normal
>>> Normal IgG,A,M.
>>> RAG1/2, ADA, Artemis: wt
>>> 
>>> Any input will be welcomed, specially concerning treatment Thanks for your help,
>>> 
>>> Luis Ignacio Gonzalez-Granado
>>> Immunodeficiencies Unit.
>>> Hospital 12 octubre. Madrid. Spain
>>> 
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