[CIS PIDD] [cis-pidd] Markedly reduced T cells with normal immunoglobulins

Mon Sep 11 23:01:44 EDT 2017

Hi - my apologies I may have missed some of this thread.   If there really is a significant population of unidentified cells, I would also consider a hematologic malignancy.  CD16 is not needed to identify NK cells, CD56+/CD3- is sufficient.

Best,

Megan

Megan Cooper, MD, PhD
Washington University School of Medicine
Cooper_m at wustl.edu<mailto:Cooper_m at wustl.edu>

On Sep 11, 2017, at 9:09 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> wrote:

Thanks everyone for your valuable inputs.

The antibodies used were anti - CD3.
For NK cells, only anti - CD56 was used. (CD16 was not used).

The test was repeated twice and the results were similar. CD45 positive - lymphocytes were first gated and then the rest of the gating was carried out.

CD4 count was 261,  and CD8 was 946.

I would try looking at recent thymic emigrants, naive and memory T cells.

Dear Dr Fabian
I shall share the raw files in next 24 hours.

As the child continues to remain sick, should I consider giving a dose of IVIG?

Will keep the group posted on the developments....

Regards
Sagar

Dr.Sagar Bhattad
MD Pediatrics, DM Pediatric Clinical Immunology and Rheumatology (PGI, CHD)
Giannina Gaslini Institute, Italy (Observership in Rheumatology)
Consultant, Pediatric Immunologist and Rheumatologist, ASTER CMI Hospitals, Bengaluru
http://www.pediatricimmunologist.in/
Aster CMI Hospital, No 43/2, International Airport Rd, Sahakara Nagar, Bengaluru -560 092, Karnataka
 (Book appointment - 08043420100)

On Mon, Sep 11, 2017 at 7:57 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> wrote:

Dr. Bhattad:

I agree with the responses of Drs. Sullivan and Hauck.  I’ve certainly seen T cell counts drop to the floor in the setting of severe infection (and, even not-so-severe infection).

The flow results are weird.  But, I think this would be a case of the devil-in-the-details.  I suggest harassing the person who did the flow cytometry.  Do the plots look good, or, was the staining all suboptimal?  (if people were skimping on the antibody, this would be why a population would not gate properly).  More importantly – what antibody did they use to identify “T cells”?  If they used anti-TCRalpha/beta, or anti-CD4 + anti-CD8 with the same color (rather than anti-CD3), then this probably gives the answer to the case (the so-called “leaky SCID with gamma/delta T cells”).  For “NK cells”, did they use both anti-CD16 and -CD56, or just one?

If all the stainings were done right, and you do have a bonafide non-CD3/4/8/19/16/56 lymphocyte (CD45+) population, you would get some innate immunologists rather excited.

Good luck.

    - Karl

From: cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net> [mailto:cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>] On Behalf Of CIS-PIDD
Sent: Monday, September 11, 2017 4:16 AM
To: CIS-PIDD
Subject: AW: [cis-pidd] Markedly reduced T cells with normal immunoglobulins

Dear Sagar,

I am not aware of a malnutrion condition that selectively reduces T cells but leaves intact B and NK cells. However, I am aware of several conditions that because of a T cell deficiency lead to a wasting disease.

Having said that and looking at the reduced T cell counts and the "missing lymphocyte population" to reach 100%, I would like to ask you the details of your gating strategy first.

Hypergammaglobulinemia does not exclude a T cell deficiency.

I would first consider TCRalpha or CD3-complex  deficiency, but almost all clasical (S)CID genes could be the cause.

You could do flow cytometry again and closesly look at the raw data (MFI):

- CD4 and CD8 T cells

- Recent thymic emigrants

- Naive and memory T cells

- alpha/beta and gamma/delta T cell

- TCR Vbeta repertoire

- T cell proliferation

Just send me a private message if you want us to do the flow cytometr for you.

Best, Fabian

PD Dr. med. Dr. sci. nat. Fabian Hauck

Oberarzt / Leiter Immundefektambulanz und Immundiagnostisches Labor
Kinder- und Jugendarzt / Kinderhämatologe und -onkologe / Fachimmunologe (DGfI)

Dr. von Haunersches Kinderspital
Klinikum der Universität München
Lindwurmstr. 4, 80337 München<https://maps.google.com/?q=Lindwurmstr.+4,+80337+M%C3%BCnchen&entry=gmail&source=g>

Tel.: (089) 4400-53931
Fax: (089) 4400-53964
E-Mail: fabian.hauck at med.uni-muenchen.de<mailto:fabian.hauck at med.uni-muenchen.de>

Das Klinikum der Universität München ist eine Anstalt des öffentlichen Rechts (AöR)
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Von: cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net> <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>> im Auftrag von CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Gesendet: Montag, 11. September 2017 09:10
An: CIS-PIDD
Betreff: [cis-pidd] Markedly reduced T cells with normal immunoglobulins

Dear all

I need your inputs in the following case......

17 months old boy, unwell for the past 4 months. Born to consanguineously married couple. Other siblings healthy.
Repeated episodes of oral thrush for the past 4 months. Some improvement with application of oral clotrimazole. Poor intake of food and loss of weight (10 kg to 9 kg). Admitted with pneumonia for the past 15 days.

On examination
Oral thrush; features of severe malnutrition (Kwashiorkor)., pedal edema; Chest - bilateral crepitations

Investigations
Anemia
No neutropenia
Lymphocyte counts 3700

Low albumin
Other liver functions, renal functions - normal

HIV - Non reactive

IgG 1640 (High)
IgA   523 (High)
IgM  110
IgE  < 1.5

NBT - normal
DHR - normal

T - 7%
B - 24%
NK - 5 %

Absolute counts
T - 332
B - 1137
NK - 227

Repeat testing after 2 days
T - 11%
B - 31%
NK - 7.7 %

Absolute counts
T - 430
B - 1172
NK - 292

T cells are markedly reduced (repeated twice, 2 days apart). What are the conditions in which T cells are markedly reduced in presence of normal/high IgG?

Is it a variant of SCID?  Leaky SCID?
(The first year of life was uneventful and this, to my knowledge is very odd for SCID)

Does severe malnutrition cause a selective reduction in T cells?

How should I evaluate this child further? Any role of IVIG in this setting?

The sum of % of T, B and NK is around 36% on first occasion and 49 % on the repeat sample ...... What could be the reasons for this? The lab expert feels it could be due to debris (but in this case there was no debris and she thus had no clue as to why the sum was not 100%)

Kindly provide your valuable inputs

Regards
Sagar

Dr.Sagar Bhattad
MD Pediatrics, DM Pediatric Clinical Immunology and Rheumatology (PGI, CHD)
Giannina Gaslini Institute, Italy (Observership in Rheumatology)
Consultant, Pediatric Immunologist and Rheumatologist, ASTER CMI Hospitals, Bengaluru
http://www.pediatricimmunologist.in/<https://urldefense.proofpoint.com/v2/url?u=http-3A__www.pediatricimmunologist.in_&d=DwMGaQ&c=ZcS_IThVDLRgSnibLQVJ9vwqRPpc3RkFqvJL1VfvJu0&r=SS5WX_zJKFGQt9gnWxXM2zj3mGuaCrOGfogIF4rsPm06T2ggGCIyqTpu8I8GvD7y&m=-6mZnv6iHcpGF419KfenN4koLYGcFnQpGMDuVPjlLUs&s=pBu5froWgSNWtRYqyUAnoVrK745fYRQ7X4gU2kZw2V8&e=>
Aster CMI Hospital, No 43/2, International Airport Rd, Sahakara Nagar, Bengaluru -560 092, Karnataka
 (Book appointment - 08043420100)

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