[CIS PIDD] [cis-pidd] patient with no CD40L expression

[Hauck, Fabian Dr.med.]

Dear Laia,

Did you check for CD25 expression?

Best wishes and hope to see you on the EBMT in Lodon?

Fabian Hauck 

-----Ursprüngliche Nachricht-----
Von: Laia Alsina Manrique de Lara [mailto:lalsina at hsjdbcn.org] 
Gesendet: Dienstag, 26. Februar 2013 17:12
An: CIS-PIDD
Betreff: RE: [cis-pidd] patient with no CD40L expression

Dear all, 

Thanks for your nice comments and suggestions: here are the results of new activation and proliferation evaluation on lymphocytes from this patient:  

-PROLIFERATION STUDIES (CFSE 7 days)
--PMA + ionomycin: normal.
--PHA: <20% --> rescued (>50%) if IL-2 (5U/ml) is added.
--PWM: normal.
--CD3+CD28+: <20% --> rescued (>50%) if IL2 is added.

-ACTIVATION STUDIES (induction of CD69 (3-6h), CD40L (24h), shedding CD62L (1h) with PHA, PWM, PMA/iono: normal, idem with and without IL-2.

Thus, the suspected deficiency is a defect in IL-2 production that limits T cell proliferation. 
We are now measuring IL-2 mRNA and protein to check for this hypothesis.


We are still unable to find an explanation for this T cell deficiency and the congenital secretory diarrhoea of the patient.

Any further suggestions regarding studies/patient management (the patient on IGIV and Co-trimoxazole with no infections).


Thank you , 

Laia


Dra. Laia Alsina
Sección de Alergia e Inmunología Clínica Hospital Sant Joan de Déu Passeig Sant Joan de Déu nº2 08950 Esplugues de Llobregat, Barcelona
+34932804000 ext 3330
________________________________________
De: Dr. Carsten Speckmann [carsten.speckmann at uniklinik-freiburg.de]
Enviado el: martes, 26 de febrero de 2013 0:35
Para: CIS-PIDD
Asunto: Re: [cis-pidd] patient with no CD40L expression

Dear Laia,

was CD40L upregulation completely lacking or reduced?
Did you check for the upregulation of other early T cell activation markers (e.g. CD25, OX40) to differentiate whether your patient has an isolated CD40L problem vs. a broader problem in T cell activation?

Kind regards, Carsten

--
Dr. med. Carsten Speckmann
Facharzt
Zentrum fuer Kinderheilkunde und Jugendmedizin Centrum fuer Chronische Immundefizienz - CCI Universitaet Freiburg Mathildenstr. 1
79106 Freiburg
Germany

phone: +49 (0)761-270 43010
mail: carsten.speckmann at uniklinik-freiburg.de
web: www.cci.uniklinik-freiburg.de




Am 25.02.13 23:53, schrieb Prescott Atkinson, M.D.:

> Hi Laia:  Was proliferative response to PMA/ionomycin checked? That is often the stimulus used to induce CD154 expression.   If defective, that might explain the failure to express CD40-L and suggest a deeper signaling defect.

>

> T. Prescott Atkinson, MD PhD, Professor and Director

>

> Division of Pediatric Allergy, Asthma & Immunology

>

> University of Alabama at Birmingham

>

> Tel: 205-939-9072

>

> Fax: 205-975-7080

>

> ________________________________________

> From: Mel.Berger at cslbehring.com [Mel.Berger at cslbehring.com]

> Sent: Monday, February 25, 2013 3:06 PM

> To: CIS-PIDD

> Subject: Re: [cis-pidd] patient with no CD40L expression

>

> On Jan 30, 2013, at 10:43 AM, "Dewton USP" <dmvascon at usp.br<mailto:dmvascon at usp.br>> wrote:

>

> Dear Laia

>

> Another disease with low expression of CD40L is ICOS deficiency, as ICOS is upstream to CD40L in its signaling pathway.

>

> Best,

>

> Dewton

>

> Dewton de Moraes Vasconcelos

> University of São Paulo School of Medicine

>

> Laia Alsina Manrique de Lara wrote:

>

> Dear all,

>

> I am contacting you regarding a 6-month old male with a congenital secretory diarrhoea (starting at 2 weeks of life) and hipogammaglobulinemia (detected at 2 weeks of life with absent IgG, low IgA that normalized at 4 months, and low IgM). Normal albumin, and no protein loss in stools or urine. Extensive microbiological studies have ruled out any viral, paratitic or bacterial gut infection.

>

> IMMUNE WORKUP:

> T and B cell phenotyping with no significant defects:

> Absloute lymphocytes: 3500/mm3.

> CD3+:   61,7% (49-85%)

> CD3+CD4+: 48,6% (27-60%)

> CD3+CD8+: 10,3% (10-55%)

> CD19+: 23% (4-50%)

> NK CD16-56+: 12,7% (2-36%)

> Extended T and B cell phenotyping:

> T cells alfa/beta: 92,3% (39-94%)

> T cells gamma/delta: 3,6% (0,9-10%)

> CD3+CD45RA+: 83% (56-95%)

> CD3+CD45RO+: 12% (2-15%)

> B cells IgM/IgD+: 91,9% (82-98%)

> B cells IgD-: 8,1% (2-15%)

> B cells IgD-CD27-: 0,8% (0,3-6%)

> Bcells IgD+CD27+: 21,3% (5-50%)

> Bcells IgM-CD38++: 2,9% (0-7%)

>

> Proliferative responses to mitogens: normal proliferation to PWM, no 

> proliferation to PHA and ConA

>

>

>

> CD40L induction after 24h: 1,3% (5-20%).

>

> Sanger sequence for CD40L shows no mutation. The sequence includes promoter regions.

>

>

> My question is:

> -which T cell deficiencies other than X-HIM could show low CD40L induction and this clinical phenotype?

>

> We suspect a primary defect in Na+/proton transporter explaining the congenital secretory diarrhoea. Could this ion transport defect explain the primary T cell activation defect (no proliferative response to mitogens).

>

> Thank you in advance,

>

>

> Dra. Laia Alsina

> Sección de Alergia e Inmunología Clínica Hospital Sant Joan de Déu 

> Passeig Sant Joan de Déu nº2 08950 Esplugues de Llobregat, Barcelona

> +34932804000 ext 3330

>

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--
Dr. med. Carsten Speckmann
Facharzt
Zentrum fuer Kinderheilkunde und Jugendmedizin Centrum fuer Chronische Immundefizienz - CCI Universitaet Freiburg Mathildenstr. 1
79106 Freiburg
Germany

phone: +49 (0)761-270 43010
mail: carsten.speckmann at uniklinik-freiburg.de
web: www.cci.uniklinik-freiburg.de


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