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

Tue Aug 29 01:03:57 EDT 2017

Hi,
I agree with both CTLA4 and lrba, but I think you should also consider STAT3-GOF.

> On Aug 28, 2017, at 23:09, CIS-PIDD <cis-pidd at lists.clinimmsoc.org> wrote:
> 
> There was no evidence of arthritis.No significant haematuria. It was transient microscopic hematuria.
> 
> 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
> Phone no: +91-9592047009, +91-9944547009
> 
>> On Tue, Aug 29, 2017 at 1:37 AM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org> wrote:
>> Dear Dr. Hauck and Dr. Yu
>> 
>> Thank you for the super fast responses.
>> 
>> Replying to your queries
>> 
>> 1. The serum IgE was normal and there was no eosinophilia
>> 2. No candidiasis ever
>> 3. The LRI episodes were mostly viral (clinically) and no extensive investigations were sent as they settle with supportive care
>> 4. The flowcytometry was sent prior to starting steroids
>> 5. Workup for CF was negative
>> 
>> 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
>> Phone no: +91-9592047009, +91-9944547009
>> 
>>> On Tue, Aug 29, 2017 at 1:20 AM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org> wrote:
>> 
>>> 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
>>> 
>>>  
>>> 
>>> Von: cis-pidd at lyris.dundee.net <cis-pidd at lyris.dundee.net> im Auftrag von CIS-PIDD <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
>>> 
>>> Phone no: +91-9592047009, +91-9944547009
>>> 
>>>  
>>> 
>>> 
>>> Rochester Regional Health Email Disclaimer
>>> This email and any files transmitted with it are confidential and intended solely for the use of the individual or entity to whom they are addressed. If you have received this email in error please delete it from your system. This footnote also confirms that this email message has been swept for the presence of computer viruses. 
>>>  
>>> ---
>>> 
>>> You are currently subscribed to cis-pidd as: vigimmc at gmail.com.
>>> 
>>> To unsubscribe click here: http://cts.dundee.net/u?id=104900047.fc9f4e54cae45cd032b86c49d3dccf32&n=T&l=cis-pidd&o=4548351
>>> 
>>> (It may be necessary to cut and paste the above URL if the line is broken)
>>> 
>>> or send a blank email to leave-4548351-104900047.fc9f4e54cae45cd032b86c49d3dccf32 at lyris.dundee.net
>>> 
>> 
>> ---
>> 
>> You are currently subscribed to cis-pidd as: vigimmc at gmail.com.
>> 
>> To unsubscribe click here: http://cts.dundee.net/u?id=104900047.fc9f4e54cae45cd032b86c49d3dccf32&n=T&l=cis-pidd&o=4548374
>> 
>> (It may be necessary to cut and paste the above URL if the line is broken)
>> 
>> or send a blank email to leave-4548374-104900047.fc9f4e54cae45cd032b86c49d3dccf32 at lyris.dundee.net
>> 
> 
> ---
> 
> You are currently subscribed to cis-pidd as: shidave at gmail.com.
> 
> To unsubscribe click here: http://cts.dundee.net/u?id=104312920.b95357c06f6e1b971ba6b89dfa47ac0d&n=T&l=cis-pidd&o=4548386
> 
> (It may be necessary to cut and paste the above URL if the line is broken)
> 
> or send a blank email to leave-4548386-104312920.b95357c06f6e1b971ba6b89dfa47ac0d at lyris.dundee.net

---
You are currently subscribed to cis-pidd as: pagid at list.clinimmsoc.org.
To unsubscribe click here: http://cts.dundee.net/u?id=96396833.5a9591ccd1e327fe6bc4d1543298c482&n=T&l=cis-pidd&o=4548922
or send a blank email to leave-4548922-96396833.5a9591ccd1e327fe6bc4d1543298c482 at lyris.dundee.net
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <https://pairlist7.pair.net/pipermail/pagid/attachments/20170829/114e9258/attachment-0001.html>