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

[John Ziegler]

Dear Eleonora

Not sure how to factor in the hypotonia to the PID diagnosis but aspiration could explain the lung problems and would not be corrected by a SCT of course.

John

From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Eleonora Gambineri
Sent: Saturday, 3 December 2011 1:07 AM
To: pagid at list.clinimmsoc.org
Subject: [CIS-PAGID] Partial CD4 deficiency, autoimmunity, bronchiectasis
Importance: High

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
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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<mailto:eleonora.gambineri at unifi.it>; e.gambineri at meyer.it<mailto: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<mailto:eleonora.gambineri at unifi.it>; e.gambineri at meyer.it<mailto:e.gambineri at meyer.it>
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