[CIS PIDD] [cis-pidd] A disorder of immunodysregulation?

Mon Aug 28 15:50:05 EDT 2017

Dr. Vignesh:

An interesting case.  Please permit me to pose a few questions to clarify the case for myself and others on the listserve –

#  What is the infant’s IgE level?  Is there any eosinophilia in the hemograms?

#  “Lower respiratory infections – no organisms isolated” could mean two very different things.  Did the infant actually have negative bacterial and viral studies of relevant specimens (blood, nasal wash, intubation/endotracheal fluid, etc.), or are there “no organisms isolated” because no one has bothered to send testing, and the infant got better with or without empiric therapy of a presumed infection (and if with, were the patient’s physicians convinced that the anti-infective therapy actually help)?

#  Any evidence of either GI or renal protein and/or cell loss?  How significant was the infant’s hematuria?  Did the infant have stool occult blood testing turn positive?

#  Was there testing done for cystic fibrosis?  Any candidiasis?  Any arthritis?  Any fever (before the prednisone was started)?

#  Do you have any functional T cell studies or TREC counts?  Did the T lymphopenia precede corticosteroid therapy, or is this information not available?

The case appears to be half-consistent with a number of potential diagnoses … but just half.  My D/Dx is all over the place … “just” malnutrition due to milk allergy, IPEX,  APECED type 2, a severe case of selective IgA deficiency (akin to Ammann and Hong, Clin Exp Imm 1970 … just without a genetic diagnosis), DOCK8, Evan’s, an early ALPS, some late onset SCID vs. Omenn, and even infantile SLE.

The only thing I might be sure of is that there was some protective effect temporally associated with breast-feeding.

          - K

Karl O. A. Yu, M.D., Ph.D., F.A.A.P.
Scientist II and Assistant Director, Center for Infectious Diseases and Immunology
RGH Research Institute | Rochester General Hospital | Rochester Regional Health
1425 Portland Ave., Room R-403, Rochester, NY   14621
Tel  585-922-3709  |  Fax  585-922-2415

From: cis-pidd at lyris.dundee.net [mailto:cis-pidd at lyris.dundee.net] On Behalf Of CIS-PIDD
Sent: Monday, August 28, 2017 3:41 PM
To: CIS-PIDD
Subject: AW: [cis-pidd] A disorder of immunodysregulation?

Dear Vignesh,

thank you for sharing this interesting case.

Even though FOXP3 was normal on the gene panel, I would propose to analyze Treg cells (CD4+CD25hiCD127loFOXP3) by flow cytometry and eventually include a CTLA4 and LRBA staining.

I am not quite sure whether the reduced T cell counts were measured under steroids - but as B and NK cells are normal, I can imagine that this might by a primary finding. Therefore I would propose to do a workup for combined immunodeficiency, i.e. naive/memory T cells (CD45RA and CCR7), recent thymic emigrants, TCR repertoire and lymphocyte proliferation testing. The findings might direct additional analysis...

I hope that helps,

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, Germany

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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, 28. August 2017 19:28
An: CIS-PIDD
Betreff: [cis-pidd] A disorder of immunodysregulation?

Dear all
A friend of mine is dealing with a perplexing case who has eczema, immunodeficiency, and autoimmunity. Any suggestions for further investigations and management would be greatly appreciated.

1 year 5 month male child born of non-consanguineous marriage was apparently normal till 7 months of age
Issues:
1. Chronic diarrhea/ failure to thrive/ malabsorption - onset at age of 10 months .He was having a steady weight gain upto 10 months and weighed 6.5 kgs at 10 months.He is currently on Soy based and proteinhydrolysate formula feeds,but persisting to have loose stools
2. Autoimmune hemolytic anemia (DCT2 + )required one transfusion for severe anemia .He is presently  on steroids (oral prednisolone)
3. Polyuria/ polydipsia multiple admission for dehydration, dyselectrolytemia.
-Modified water deprivation test which was not conclusive of Diabetes Insipidus
had microscopic hematuria managed conservatively.
4. Immunodeficiency - has low serum IgA levels - 3mg/dl (IgG/ M/E normal)
                                     absolute CD3 CD4 and CD8 below normal
5.History of eczema at 5 months of age.Now has dermatitis and dry skin?Nutritional
Past History:Treated for Lower respiratory infections -3 episodes from 7 to 10 months-Treated with nebulisations- no organisms isolated
Birth History:
Preterm/35 weeks/Born by emergency LSCS- Antenatal oligohydramnios
Was in NICU for 4 days/CPAP for one day.Exclusively breast fed upto 6 months of age
Family history : Mother was being treated for autoimmune hemolytic anemia, had 2 spontaneous abortions, diagnosed to have APLA during this pregnancy was treated with heparin.
Maternal grand father h/o rheumatoid arthritis
WORK UP:
Complete Hemogram-Hb LOW (5 g/dl at presentation)  total white cells-19300 (N67, L30, M 2, E 1) PLATELETS low normal 1.5 to 2 lac ,Mean Platelet Volume-Normal
Direct Coombs test ++
Renal function tests- serum creatinine normal
LFT: SGOT/ SGPT- normal, Serum albumin 2.3, alkaline phosphatase 770
STOOL ROUTINE CRYPTOSPORIDIUM OOCYST ++ TREATED ADEQUATELY FOR THE SAME
stool ocult blood negative.
Retoviral status-Negative
Serum- C3-27.4 (80-156)-low
Serum C4-<6.65(12-43)-low
ANA(Immunoflourescence)-Weak positive
Extended Panel of Antibodies-Multiple antibodies were positive
Anticentromere antibody=39.4(<20)
Antii JO-1                            =45.25(<20)
Anti-Scl-70                          =40.45(<20)
Antismith                            =34.18(<20)
SSA                                       =39.91(<20)
U1RNP Ab                           =32.5(<20)
Anti cardiolipin Ab            =7.45(12)
Anti phopholipid Ab IgM-18.47(<10)
Lupus anti coagulant =Negative
RA factor +
GI scopy UGI scopy AND Colonoscopy normal
Biopsy mild chronic duodenitis
T3, T4 , TSH normal
Celiac antiobodies -TTG-Ig A negative
Anti gliadin antibody + =34.18(<25)
Serum Immunoglobulin Prolife
IgG=611 mg/dl(340-1200)
IgA=3 mg/dl(15-110)
IgM=67 mg/dl(45-200)
Flowcytometry

CELL

RESULT

REFERENCE

UNIT

CD3+(Tcells)

18.64

53-81

%

CD3+(Absolute count)

664

1460-5440

Cells/ul

CD3+CD4+

9.52

31-54

%

CD3+CD4+(Absolute count)

339

1020-3600

Cells/ul

CD3+CD8+

7.88

16-38

%

CD3+CD8+(Absolute count)

281

570-2230

Cells/ul

CD3-/CD19+

54.90

11-45

%

CD3-/CD19+(Absolute count)

1536

430-3300

Cells/ul

CD3-/CD56+

10.52

3-19

%

CD3-/CD56+(Absolute count)

294

80-340

Cells/ul

T4/T8 RATIO

1.21

1.17-6.62

Targeted gene sequencing(Exonic) for Primary Immunodeficiency: No mutations detected in FOXP3 / STAT1/ STAT5B/IL10/IL10 RA/IL10RB/IL2RA

Kindly provide inputs for further management.

Thank you.

Vignesh P
MD Pediatrics,
DM resident in Pediatric Clinical Immunology and Rheumatology (Jan 2015- Dec 2017),
Allergy Immunology Unit, Advanced Pediatrics Center,
Postgraduate Institute of Medical Education and Research,
Chandigarh, India. 160012.
E mail: vigimmc at gmail.com<mailto:vigimmc at gmail.com>
Phone no: +91-9592047009, +91-9944547009

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