[CIS PIDD] Making Diagnosis of LAD -leukocyte adhesion defect- 1

[Verbsky, James]

Oner

Was the anal abscess sterile as well?  Were they on Abx?  My question is whether these are  really infections.  How old were they when the abscesses were discovered?  I would expect there to be bacteria in the abscess if off Abx.  The fact that the WBC came down and no delayed separation would argue against LAD. If the WBC came down on Abx…its harder to interpret.

I would suggest a functional assay.  Migration studies could be helpful if available.  An uncontrolled but easy way to test this is to look at blasting lymphocytes to determine if they aggregate after 2-3 days.  They should form tight round aggregates.  This is integrin dependent.  We have done this with CD18 blocking antibodies and the cells divide but do not form the aggregates.  Similar results were seen with a RAC2 mutant patient.

James


James W. Verbsky MD/PhD
Associate Professor of Pediatric,s and Medical Microbiology and Genetics
Medical College of Wisconsin
Milwaukee, WI  53211
jverbsky at mcw.edu<mailto:jverbsky at mcw.edu>
414-266-6701 (phone)
414-266-6695 (fax)



From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Daniel Conway
Sent: Wednesday, July 11, 2012 8:24 AM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS PIDD] Making Diagnosis of LAD -leukocyte adhesion defect- 1

Is there consanguinity?

Is there any region of homozygosity on microarrays?

Dan

Sincerely,
Daniel H. Conway, MD
Assistant Professor of Pediatrics
St. Christopher's Hospital for Children
Drexel University College of Medicine

On Jul 11, 2012, at 8:53 AM, "Oner Ozdemir" <oner.ozdemir.md at gmail.com<mailto:oner.ozdemir.md at gmail.com>> wrote:
Dear Dr. Amos;

Thanks very much for your input.
WBC count is still within normal, ranged from 29,100 (initial) to 12,000 /mm3 in a couple of days. There was no delayed separation of cord.
This patient was asphyctic at birth, then intubated and admitted NICU.
Due to sterile brain abscesses, we investigated expressions and found to be low just on the lymphocytes. Dihydrorhodamin 123 (DHR) was normal in this patient.
- Her twin has had anal abscess during this time. Twin's DHR was normal. Her twin has similar low expressions of CD11a/b/c-CD18 complex as well.
- Dr Amos, You said that more than 80%, does this mean CD11a/b/c-CD18 complex expression should be more than 80% or CD18 expression in general?

Best regards;


On Wed, Jul 11, 2012 at 3:02 PM, Amos Etzioni <etzioni at rambam.health.gov.il<mailto:etzioni at rambam.health.gov.il>> wrote:
Dear Oner
First of all we need to know what is the leukocyte count and the clinical symptoms ( delay separation of the cord?). If indeed the WBC is very high and there are symptoms characteristic for LAD I, I would go for genetic analysis. There are rare case ( Hogg et al. JCI 1999) in which the mutation caused a nonfunctional but expressed CD18.
As far as I know there is no fix number for CD18 expression, but one can say that normally we see more than 80% expression
Amos

Amos Etzioni MD
Professor of Pediatrics and Immunology
Director - Meyer Children's Hospital
Bat- Galim, Haifa, Israel 31096
Tel- 972-4-854 2936
Fax- 972-4-854 1870
Email - etzioni at rambam.health.gov.il<mailto:etzioni at rambam.health.gov.il>



From: pagid-bounces at list.clinimmsoc.org<mailto:pagid-bounces at list.clinimmsoc.org> [mailto:pagid-bounces at list.clinimmsoc.org<mailto:pagid-bounces at list.clinimmsoc.org>] On Behalf Of Oner Ozdemir
Sent: Wednesday, July 11, 2012 2:20 PM
To: pagid at list.clinimmsoc.org<mailto:pagid at list.clinimmsoc.org>
Subject: [CIS PIDD] Making Diagnosis of LAD -leukocyte adhesion defect- 1

Dear All,

We are dealing a patient suggestive of leukocyte adhesion defect -1.

The patient is borne with C/S, G3P3, pair of twins, with sterile cerebral abscesses. And there is a sibling to this twins is 5-year-old and healthy.

CBC: normal, Ig GAME: normal, lymphocyte subpopulations: normal in the patient.

On this patient, flow cytometry revealed that borderline low CD18 expression (80 %) on lymphocytes, but neutrophil and monocyte CD18 expression within normals (above 90 %).

And the lymphocyte expressions of CD11a /CD18: 19 %; CD11b /CD18: 2 %; CD11c /CD18: 11 % seemed to be low.


My questions are:

1- Even though total CD18 expression on lymphocytes is borderline low; can we make a diagnosis of LAD with one of the lower expresions of CD11a /CD18, CD11b /CD18, CD11c /CD18 on just lymphocytes?

2- Should these low expressions of CD11a /CD18, CD11b /CD18, CD11c /CD18 with CD18 epression be on the monocytes and neutrophils in addition to lymphocytes at the same time to make a diagnosis?

3- Any normal reference values for CD11a /CD18, CD11b /CD18, CD11c /CD18 expressions in children?


Best Regards;

Oner Ozdemir, MD














--


Öner Özdemir, MD
Chief and Assoc. Prof. Pediatrics
Republic of Turkey, Ministry of Health, İstanbul Medeniyet University,
Göztepe Research and Training Hospital
Göztepe, Kadıköy, İSTANBUL -TÜRKİYE.








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--
Öner Özdemir, MD
Chief and Assoc. Prof. Pediatrics
Republic of Turkey, Ministry of Health, İstanbul Medeniyet University,
Göztepe Research and Training Hospital
Göztepe, Kadıköy, İSTANBUL -TÜRKİYE.





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