[CIS PIDD] [cis-pidd] Renal Disease and CVID - IVIG replacement on haemodialysis (HD)

Mon Apr 25 21:37:13 EDT 2016

Hello Stan,
Another thought which comes to my mind looking at the unusually high rate of IgG catabolism is a variant or mutation in the FCGRT gene which encodes for the neonatal Fc receptor (FcRn). Variable number of tandem repeat changes in the promoter region of FCGRT have been seen in CVID pts who have higher and more frequent requirement of IGIV. Another simple test to look for intestinal losses would be serum albumin. Both IgG and albumin escape catabolism by a FcRn mediated uptake and recirculation.
Regards,
Amit --Dr. Amit Rawat MD (Pathology) PDCC (Laboratory Immunology) PDCC (Nephropathology) MAMS
Additional Professor, Paediatric Allergy & Immunology UnitDepartment of Paediatrics, Advanced Paediatric CentrePostgraduate Institute of Medical Education & ResearchSector 12, Chandigarh 160012. Phone: +91-172-2755682 (Off), +91-99-14208486 (Mob) Email: rawatamit at yahoo.com, amitrawat2002 at rediffmail.com

      From: CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
 To: CIS-PIDD <cis-pidd at lyris.dundee.net> 
 Sent: Tuesday, April 26, 2016 3:39 AM
 Subject: Re: [cis-pidd] Renal Disease and CVID - IVIG replacement on haemodialysis (HD)

Thanks so much to Kate and Nacho for your responses and very helpful comments.
On Kate’s first issue of how best to achieve a trough serum IgG level that is required to keep her free of most infections (ideally targeted at 8-10 g/L), her highest level of serum IgG was in July 2014 - 7.14 g/L. Since then she has been on SC Beriglobin via a “push” method of delivery, & her serum IgG has been around 4-5 g/L. She has recently been administering 16 ml of Beriglobin-P 5 days a week (12,8 grams of IgG weekly) which is a higher dose than previously, and the latest serum IgG on 21 April was certainly improved at 6.49 g/L. We just need to exclude intestinal losses as Nacho suggested, and I will  arrange an alpha-1 anti-trypsin clearance. Not sure how I can address the issue of elevated catabolism of IgG in a patient on weekly SC. 
I will also look into how we can arrange sequencing to diagnose a "CVID-like" monogenic disorder.
Thanks again.
Regards,
Stan
From: CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
Reply-To: CIS-PIDD <cis-pidd at lyris.dundee.net>
Date: Thursday 21 April 2016 at 12:31 PM
To: CIS-PIDD <cis-pidd at lyris.dundee.net>
Subject: Re: [cis-pidd] Renal Disease and CVID - IVIG replacement on haemodialysis (HD)

I think there are two components to this story.  The first is how to best achieve a trough level that is sufficient to prevent most infections.  The second is to determine if this CVID patient has a monogenic disorder that you might treat completely differently.
In general, when we see loss or high catabolism of IgG, it may not be appropriate to target the usual trough level.  Always a goal, but the side effects/cost/inconvenience may not allow it.  I think more frequent subQ infusions often will allow you to get higher levels but in some patients, the losses are simply too overwhelming and it is like pouring the IVIG down the sink. That doesn’t seem to be case for your patient and I think tweaking the immunoglobulin regimen may help you get closer to goal troughs. 
To come back to the second question- when there is a lot of autoimmune disease, I think of monogenic disorders that have a CVID phenotype. Sometimes, weirdly, immune suppression can help the trough by decreasing catabolism.  I’m not sure how easy it is for you to get access for sequencing but a completely different approach would be to try to determine if this is a PI3 kinase defect or other monogenic form and then you might try to target that pathway.
Kate
Kate Sullivan, MD PhD
Wallace Chair Chief of Allergy ImmunologyARC 1216 CHOP
3615 Civic Center Blvd.
Philadelphia, PA 19104
(p) 215-590-1697(f) 267-426-0363
------------------------------------------------------------------------------------------------------------------------Dear Stan,I would definitely go for SCIG (and be prepared to combine weekly scig + monthly ivig if the desired levels are not achieved). I would recheck intestinal losses are not present.Hope this helpsNacho
ADDRESS:
Luis I. Gonzalez-Granado. MD.
ADDRESS:
Immunodeficiencies Unit. 
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Hospital 12 de octubre.

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Research Institute Hospital 12 octubre (i+12)   

ADDRESS:
Av. Cordoba S/N. 28041. Madrid. Spain
Tel. 0034606732959 /  0034913908569  /  Fax 0034913908772
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luisignacio.gonzalez at salud.madrid.org
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ORCID ID:  orcid.org/0000-0001-6917-8980

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Researcher ID: B-9257-2009
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ResearchGate:https://www.researchgate.net/profile/Luis_Gonzalez-Granado 
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LinkedIn:  https://es.linkedin.com/in/nachgonzalez

On Apr 21, 2016, at 6:02 AM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org> wrote:
 Dear colleagues,  I posted a query a year ago concerning a  36 year-old lady with CVID who had several complications including bronchiectasis, massive splenomegaly and hypersplenism requiring splenectomy, and  liver disease with nodular regenerative hyperplasia. While receiving 3% sucrose IVIG replacement she developed renal impairment. Renal biopsy showed interstitial nephritis and she was switched to SC Beriglobin by “push” administration. Unfortunately her renal failure progressed and she has required HD. The problem is that we have not been able to get her serum IgG at the required trough level of 7-8 g/L (it’s usually only 5 g/L) and she has had continued sinus infections, recently complicated by staphylococcal infection of the AV graft.   My questions are:  1.      Since she is on HD twice weekly, would there be any concern about reverting to 3% sucrose IVIG preparation which would permit higher doses of Ig replacement,  and a better chance of reaching required serum IgG level? (I guess the alternative would be to administer SC Ig via a pump to try for optimal levels).  2.      Are there any other considerations regarding the kinetics of IVIG in a patient on HD, any factors related to frequency of administration, catabolism of the product, etc? Presumably we would simple monitor the serum IgG weekly to determine dose and frequency of administration.    3.      Any other advice?  I would appreciate any input, suggestions, advice.  Thanks & Regards,  Stan  Stanley Ress
Emeritus Associate Professor of Medicine, UCT Specialist physician & Clinical Immunologist
UCT Private Academic hospital, Anzio Road, Observatory,
Cape Town, 7925
South Africa
TEL:INTERN. + 2721-4421966 or 4421816
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