[CIS PIDD] [cis-pidd] Unusual case of combined immunodeficiency with normal numbers of CD4 and CD8 cells [Bulk]

CIS-PIDD cis-pidd at lists.clinimmsoc.org
Wed Jun 29 11:46:58 EDT 2016 

I appreciate the thoughts from everybody.  We are going to get a few more tests done on his lymphocytes to see if we can get closer to a diagnosis, then will probably proceed to molecular diagnostics.

We were already planning on a cheek swab for DNA because of the need to minimize blood tests, but Sergio's reminder about possible contaminating maternal cells is an important warning to remember.

Will keep you posted as we get data!

Howard

Howard M. Lederman, M.D., Ph.D. 
Professor of Pediatrics, Medicine and Pathology 
Division of Pediatric Allergy and Immunology 
Johns Hopkins Hospital - CMSC 1102 
600 N. Wolfe Street 
Baltimore, MD 21287-3923 
Phone: 410-955-5883 
Fax: 410-955-0229 
Email: Hlederm1 at jhmi.edu 

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-----Original Message-----
From: CIS-PIDD [mailto:cis-pidd at lists.clinimmsoc.org] 
Sent: Wednesday, June 29, 2016 11:36 AM
To: CIS-PIDD <cis-pidd at lyris.dundee.net>
Subject: Re: [cis-pidd] Unusual case of combined immunodeficiency with normal numbers of CD4 and CD8 cells [Bulk]

Howard,
If you decide to ³go molecular² on this pt's diagnosis and maternal engraftment concern is an issue, it will probably be safer to get gDNA from a buccal swab or a other non-hematopoietic source less likely to be contaminated with maternal lymphocytes.
Sergio

On 6/29/16, 11:17 AM, "CIS-PIDD" <cis-pidd at lists.clinimmsoc.org> wrote:

>Howard
>
>Agree with other comments.  The defective mitogens could be from 
>Ora1/Stim1.  Any hypotonia?  CD25 deficiency could also be involved.  
>Is the patient small?  IGF-BP3 or IGF1 levels?  Agree that this looks 
>like an activation defect, and both Ora1/Stim1 and CD25 can have normal
>numbers of lymphocytes.   We do CD25 and CD69 activation studies
>clinically if that would help.
>
>Best
>
>James Verbsky MD/PhD
>
>
>From: CIS-PIDD
><cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
>Reply-To: CIS-PIDD
><cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
>Date: Tuesday, June 28, 2016 at 3:38 PM
>To: CIS-PIDD 
><cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
>Subject: Re: [cis-pidd] Unusual case of combined immunodeficiency with 
>normal numbers of CD4 and CD8 cells [Bulk]
>
>Hi Howard,
>
>I agree that maternal T cell engraftment should be looked for. The 
>patient does not meet criteria for Omenn (no rash, no eosinophilia, no 
>lymphadenopathy), but leaky SCID is a possibility. Also, T cell 
>activation defects may present like this. I agree with looking for 
>naïve/memory T cells and T cell oligoclonality. I would also send out 
>for targeted gene sequencing using an extensive SCID panel, such as the 
>one at Baylor, Gene Dx, or NIH.
>
>Best regards
>
>Gigi
>
>
>Luigi D. Notarangelo
>Turki bin Abdel-Aziz Al-Saud Professor of Pediatrics Division of 
>Immunology Boston Children¹s Hospital Harvard Medical School
>
>tel: (617)-919-2277
>email: 
>luigi.notarangelo at childrens.harvard.edu<mailto:luigi.notarangelo at childr
>ens
>.harvard.edu>
>
>
>From: CIS-PIDD
><cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
>Reply-To: CIS-PIDD
><cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
>Date: Tuesday, June 28, 2016 at 4:08 PM
>To: CIS-PIDD 
><cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
>Subject: [cis-pidd] Unusual case of combined immunodeficiency with 
>normal numbers of CD4 and CD8 cells [Bulk]
>
>We are seeing a  6-month old boy, born at term and previously healthy, 
>until he developed progressive tachypnea beginning at age 5 months.  He 
>is a beautiful-looking baby without dysmorphic features,  and with 
>normal teeth , nails and hair.  He was eventually noted to have a 
>severe diffuse interstitial pneumonia and pneumocystis was identified by bronchoscopy.
>We assumed that he had SCID and started a work-up with an unexpected 
>combination of results because he has normal numbers of CD4 and CD8
>Tcells:
>
>WBC 8540 with 59% lymphs (5038), 37% PMNs, and 5% monos Over the course 
>of hospitalization , has had WBC as high as 24,440 with 82% lymphs 
>though both WBC and ALC have since returned nearly to above baseline
>
>56% CD3
>26% CD4 (2729)
>27% CD8
>36% CD19
>36% CD20
>5% CD16/56
>
>IgG 409
>IgA <7
>IgM 92
>
>HIV PCR negative.
>
>I had originally considered X-linked hyper-IgM as a possible 
>explanation for normal T cell numbers, the immunoglobulin, and PCP.
>However, have just finished mitogen assay with another unexpected 
>result for a patient with completely normal T cell numbers:
>
>Stimulus                               Patient                 Control
>
>Unstim                                 146 + 90                185 + 50
>
>PHA                                       691 + 329             141,710 +
>14,498
>
>Con A                                    422 + 229             53,231 +
>474
>
>SpA                                        338 + 3
>14,388  + 4,270
>
>We also know that he has normal MHC class ­I expression, but the sample 
>was QNS for class-II expression.
>TRECs were not done since he was born before Maryland started screening 
>for SCID, but we will get that done this week.
>
>
>Are there any tests that people can suggest that will direct the next 
>stages in the work-up, or should we simply charge ahead with a whole 
>exome (or whole genome) sequence?
>
>Howard
>Howard M. Lederman, M.D., Ph.D.
>Professor of Pediatrics, Medicine and Pathology Division of Pediatric 
>Allergy and Immunology Johns Hopkins Hospital - CMSC 1102
>600 N. Wolfe Street
>Baltimore, MD 21287-3923
>Phone: 410-955-5883
>Fax: 410-955-0229
>Email: 
>Hlederm1 at jhmi.edu<https://urldefense.proofpoint.com/v2/url?u=https-3A__
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