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

[stephan.ehl at uniklinik-freiburg.de]

Ele,

- just to make sure: HIV excluded?
- consider DOCK8
- perform radiosensitivity testing
- with bronchiectasis at this age, go for transplantation. To me, in this
case loosing the window of opportunity weighs more than the risk of an
epithelial component.

Beste Grüße

Prof. Dr. Stephan Ehl
Wissenschaftlicher Direktor

UNIVERSITÄTSKLINIKUM FREIBURG
CCI - Centrum für Chronische Immundefizienz

Breisacher Str. 117 - 2. OG, 79106 Freiburg i. Brsg., Germany
Telefon: +49(0)761.270-77300
Sekretariat +49(0)761.270-77550  fax +49(0)761.270-77600
e-mail: stephan.ehl at uniklinik-freiburg.de





Von:	Eleonora Gambineri <eleonora.gambineri at unifi.it>
An:	pagid at list.clinimmsoc.org
Datum:	02.12.2011 15:07
Betreff:	[CIS-PAGID] Partial CD4 deficiency, autoimmunity,
            bronchiectasis
Gesendet von:	pagid-bounces at list.clinimmsoc.org



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
********************************************************************