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

[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
********************************************************************

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