[CIS-PAGID] Partial CD4 deficiency, autoimmunity, bronchiectasis

[Michael Albert]

Hi Ele,
I agree with all of the above.
Rule out DOCK8, STIM1 and ORAI1.
Proceed with HSCT.
Best,
Michael

2011/12/4 Eleonora Gambineri <eleonora.gambineri at unifi.it>:

> Thank you all for the useful inputs!

> Will surely look at DOCK8 and wait results from radiosensitivity assay that

> is ongoing already.

>

> Best wishes,

> Ele

>

> --

> Dott.ssa Eleonora Gambineri

> Ricercatore Universitario

> Universita' degli Studi di Firenze

> Dipartimento della Salute della Donna e del Bambino

> Ospedale Pediatrico "Anna Meyer"

> Viale Gaetano Pieraccini,24

> 50139 FIRENZE

> Tel 055 5662405 (ufficio)/055 5662606 (reparto TMO)

>

> Fax 055 4221012

> e-mail: eleonora.gambineri at unifi.it; e.gambineri at meyer.it

>

>

> Eleonora Gambineri, MD

> Researcher/Assistant Professor

> University of Florence

> Department of Sciences for Woman and Child's Health

> "Anna Meyer" Children's Hospital

> Viale Gaetano Pieraccini,24

> 50139 FIRENZE

> ITALY

> Tel +39 055 5662405 (office)/055 5662606(BMT ward)

>

> Fax +39 055 4221012

> e-mail: eleonora.gambineri at unifi.it; e.gambineri at meyer.it

>

>

> ----- Messaggio da fabriciopmonteiro at gmail.com ---------

>    Data: Fri, 2 Dec 2011 13:19:09 -0200

>      Da: Fabrício Prado Monteiro <fabriciopmonteiro at gmail.com>

> Rispondi-A:pagid at list.clinimmsoc.org

>  Oggetto: Re: [CIS-PAGID] Partial CD4 deficiency, autoimmunity,

> bronchiectasis

>       A: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>

>      Cc: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>

>

>

>

>> Consider DOCK8!

>>

>> Dr. Fabrício Prado Monteiro

>>

>> Imunologista & Pediatra

>>

>> HFA-Dep. de Alergologia

>>

>> HRAS-Dep. de Pediatria.

>>

>> Il giorno 02/dic/2011, alle ore 12:45, "Dr. Carsten Speckmann"

>>  <carsten.speckmann at uniklinik-freiburg.de> ha scritto:

>>

>>> As pointed out by you there is for sure a T cell problem. What is  the

>>> picture of the muscular hypotonia? Enamel defect?

>>> Ca chanelopathies present with normal absolute lymphocytes,  clinical T

>>> cell deficiency and sometimes (i.e. STIM1) with  autoimmunity.

>>>

>>> Carsten

>>>

>>> Am 02.12.11 15:07, schrieb Eleonora Gambineri:

>>>>

>>>>

>>>> Dear all I would like your inputs on the case below:

>>>>

>>>>  21 mo/old girl

>>>>

>>>> FAMILY HISTORY unremarkable

>>>>

>>>> MEDICAL HISTORY: hx at birth unremarkable. At 7 mo of age she  started

>>>> to suffer of recurrent respiratory infections (mainly  pneumonitis and

>>>> bronchitis); at 15 mo: ? Enterovirus encephalitis  (no evidence at brain MRI

>>>> and EEG, but positive PCR in liquor);  afterwards she had 4 pneumonitis

>>>> (June-Sept 2011) with slow recovery

>>>>

>>>>  LAB W/U

>>>>

>>>>  Normal LFTs/U&E

>>>>

>>>>  Immunological W/U:

>>>>

>>>> WBC 9900/ul L 27.6% (2732/ul), Eo 22.6% (2237/ul) N 40.4% B 1.7%,  M

>>>> 3,8%; Hb 11 g/dl, ferritin 2,7 ng/ml

>>>>

>>>> Partial CD4 deficiency (400-500/ul) with low/absent CD4/CD45/CD31+

>>>>  cells (absent TRECs) and expansion of memory phenotype both in CD4  and CD8

>>>> subsets. Normal B cell numbers with good percentage of  memory B cells.

>>>>

>>>> Antibody responses: POSITIVE to measles and varicella, NEG to  tetanus,

>>>> HBV, difteria, HSV IgG positive, EBV IgG/IgM negative,  HHV6 IgG/IgM

>>>> negative

>>>>

>>>> IgG 900 mg/dl, IgA64 mg/dl, IgM 233 mg/dl (increased), IgE negative

>>>>

>>>> TCR repertoire: high Vb6-5, 6-6, 6-9 (on CD8)…not sure if done on CD4

>>>>

>>>> In vitro lymphocyte proliferation assay: low response to PHA and

>>>>  aCD3/CD28+IL2 (However, it was not confirmed in another lab)

>>>>

>>>> Alpha feto-protein: slightly deranged (13 UI/ml, NV 0.1-4.9)

>>>>

>>>> Coombs POSITIVE IgG; ANA POSITIVE (1:1280); aTPO POSITIVE (normal

>>>>  thyroid function)

>>>>

>>>> Infection W/U

>>>>

>>>> CMV PCR POSITIVE on BAL; Pseudomonas Positive on BAL

>>>>

>>>> CMV, Adeno, EBV PCR negative on blood

>>>>

>>>>  IMMAGING:

>>>>

>>>>  Chest CT: bronchiectasis; Thyroid US: normal, lateral-cervical LN  with

>>>> increased size; Abdomen US: nil; Heart US: nil; Thymus should  be present,

>>>> but ask to review the scan (results still pending)

>>>>

>>>>  O&E

>>>>

>>>> Normal growth

>>>>

>>>> No signs of intestinal malabsorption

>>>>

>>>> Ligamentous Hyperlaxity

>>>>

>>>> Muscle hypotonia (normal EMG at lower body, partly altered at  upper

>>>> body, anti AchR Ab ongoing)

>>>>

>>>> No dimorphisms (she was reviewed by Geneticist); No hair  alterations;

>>>> No bone abnormalities (at femur X Ray, total skeleton  X-Ray TBD)

>>>>

>>>> No rash, but diffuse itchiness

>>>>

>>>> Chest: when in good conditions, crackles all over the chest with  minor

>>>> distress. SatO2 in AA 93%, with episodes of desaturation at  night. She is

>>>> at the moment on FKT.

>>>>

>>>> Liver: 1-2 cm below costal margin

>>>>

>>>> CV: systolic hypertension of unknown origin (no renal impairment,  no

>>>> steroid treatment)

>>>>

>>>>  DIFFERENTIAL

>>>>

>>>>  At the moment the following condition have been excluded:

>>>>

>>>> - HLA I and II deficiency

>>>>

>>>> - ADA/PNP deficiency

>>>>

>>>> - RAG1/RAG2 mutations

>>>>

>>>> - IL7Ra deficiency

>>>>

>>>> - DGS (CGH array negative)

>>>>

>>>> - AT (aFP 13 is it indicative? no clinical signs?)

>>>>

>>>> - CHH, sequencing of RMRP ongoing at the moment

>>>>

>>>> Any other suggestion?

>>>>

>>>> We are assessing the patient to evaluate a possible HSCT from her

>>>>  matched-sibling brother, although given the unknown nature of her  immune

>>>> defects and the compromised pulmonary conditions do you  think it is

>>>> feasible to proceed? My worry is regarding the thymus.  What if there is an

>>>> unknown thymus defect (immune deficiency and  dysregulation)? This might

>>>> question the immune reconstitution  after HSCT. On the other hand the

>>>> infection history of this girl  as well as her immune function do not

>>>> suggest a mild disease  course and BMT seems the only option. I know it is a

>>>> tricky  question, but I will really appreciate your help.

>>>>

>>>> Thanks for your cooperation!

>>>>

>>>> Best wishes,

>>>>

>>>> Eleonora

>>>>

>>>> *******************************************************************

>>>> Dott.ssa Eleonora Gambineri

>>>> Ricercatore Universitario

>>>>

>>>> Universita' degli Studi di Firenze, Dipartimento di Scienze per la

>>>>  Salute della Donna e del Bambino

>>>> Ospedale Pediatrico "Anna Meyer", Dipartimento di Oncoematologia-Unità

>>>> TMO

>>>> Viale Gaetano Pieraccini, 24

>>>> 50139 FIRENZE

>>>> Tel 055 5662405 (ufficio)

>>>>       055 5662606 (reparto T.M.O.)

>>>> Fax 055 4221012

>>>> e-mail: eleonora.gambineri at unifi.it; e.gambineri at meyer.it

>>>>

>>>> Eleonora Gambineri, MD

>>>> Researcher/Assistant Professor

>>>>

>>>> University of Florence, Department of Sciences for Woman and Child's

>>>> Health

>>>> "Anna Meyer" Children's Hospital, Department of Haem/Onc-BMT Unit

>>>> Viale Gaetano Pieraccini, 24

>>>> 50139 FIRENZE

>>>> ITALY

>>>> Tel +39 055 5662405 (office)

>>>>       +39 055 5662606 (BMT Unit)

>>>> Fax +39 055 4221012

>>>> e-mail: eleonora.gambineri at unifi.it; e.gambineri at meyer.it

>>>> ********************************************************************

>>>>

>>>

>>>

>>> --

>>> 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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