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

Wed Jun 29 11:35:50 EDT 2016

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 childrens
>.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__mob
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