[PAGID] oral Ig

[Sorensen, Ricardo]

Hi, Oral immune serum globulin has worked marvels in some patients. A few years ago I prepared the summary I am copyng below. Since that summary we have treated one more patient with severe rotavirus infections and it also stopped the diarrhea in a few days.

Before copying the summary, you should also check into the possibility that your patients may have developed food allergy after transplantation. If needed, I dig up the reference somewhere.

Here is the summary about the use of oral ISG:

Oral administration of IgG

Human IgG was shown to survive passage through the gastrointestinal tract in an immunologically active form and suppress rotavirus excretion in patients who failed to respond to monthly IVIG infusions [Losonsky, 1985 #60].  The dose was 150 mg/kg day of a 5% IVIG preparation 

Losonsky GA, Johnson JP, Winkelstein JA, et al.: Oral administration of humans serum immunoglobulin in immunodeficient patients with viral gastroenteritis, J Clin Invest 76: 2362, 1985.

Subsequently, oral IVIG was also used effectively in patients with primary immunodeficiency syndromes and chronic diarrhea of unspecified etiology [Melamed, 1991 #85].  The dose was 1,65 gm twice a day for two 8 and 9-year old patients.

Melamed I, Griffiths AM, Roifman CM: Benefit of oral immune globulin therapy in patients with immunodeficiency and chronic diarrhea., J Pediatr 119: 486, 1991.

At the Department of Pediatrics, LSU Health Science Center and Children's Hospital in New Orleans, we have anecdotal experience of oral IgG use in two patients:

One adolescent patient with cartilage hair hypoplasia and common variable hypogammaglobulinemia wase successfully treated a life-threatening, secretory cryptosporydial diarrhea in with daily oral administration of an IVIG preparation. This patient had not responded to earlier drug therapy and an increase in IVIG dose and frequency of administration.  The dose was 5 g/day. The patient improved and treatment was discontinued after 7 days. It needed to be repeated 1 year later for a similar episode of diarrhea. 

One patient with X-linked SCID and chronic mild diarrhea with rotavirus excretion was 
Treated with oral IVIG, 150 mg/kg/day for several months. This treatment improved the diarrhea, but did not stop rotavirus excretion. After an attempt to discontinue this treatment,  watery diarrhea recurred within two days and Improvement when oral IVIG restarted.

(Sorensen, unpublished observations).

In conclusion, oral IgG should be considered for patients with primary immunodeficienciy syndromes who develop severe or chronic diarrheas of various etiologies that do not respond to conventional treatment.

Ricardo Sorensen, M.D.
New Orleans

PS. Higher doses if IgIV are unlikely to make a difference
 

-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Howard M Lederman
Sent: Monday, June 29, 2009 9:57 AM
To: pagid at list.clinimmsoc.org
Subject: Re: [PAGID] oral Ig

You may want to look at this old article documenting that oral Ig can survive the challenges from the stomach and duodenum.

Losonsky GA, Johnson JP, Winkelstein JA, Yolken RH. J Clin Invest. 1985 Dec;76(6):2362-7. 
Oral administration of human serum immunoglobulin in immunodeficient patients with viral gastroenteritis. A pharmacokinetic and functional analysis.

We examined the pharmacokinetics and immunological activity of human serum immunoglobulins (HSG) possessing anti-rota-virus activity which were orally administered to three children with primary immunodeficiency syndromes and prolonged gastrointestinal excretion of rotavirus. Detailed analysis of the excretion of immunoglobulins labeled with biotin or I125 revealed that approximately 50% of the recovered radioactivity was excreted in the stools over a 3-d period. Approximately half of the excreted radioactivity recovered in the stool was in a macromolecular form with immunological activity. The remainder of the recovered radioactivity was excreted in the urine as low molecular weight fragments or free iodide. In addition, immunological and chromatographic analyses revealed that the oral administration of HSG resulted in the generation of rotavirus-specific immune complexes in the gastrointestinal tract with a subsequent decrease in the presence of uncomplexed rotavirus antig
en. These studies indicate that orally administered HSG can survive passage in the gastrointestinal tract in an immunologically active form, and that the oral administration of immunoglobulins with specific reactivities has potential for the prevention or treatment of gastrointestinal infections.


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 jhem.jhmi.edu

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----- Original Message -----
From: YaeJean Kim <yaejeankim at skku.edu>
Date: Monday, June 29, 2009 9:08 am
Subject: Re: [PAGID] oral Ig
To: pagid at list.clinimmsoc.org



> Thanks for your response. 

>  

>  Yes, I was also concerned about the possibility that the Ig would get 

> all

>  destroyed while passing through GI tract. Anyway, I am also considering

>  intravenous IgG as well. 

>  

>   

>  

>  YaeJean 

>  

>    _____  

>  

>  From: pagid-bounces at list.clinimmsoc.org

>  [ On Behalf Of Daniel Conway

>  Sent: Saturday, June 27, 2009 8:03 PM

>  To: pagid at list.clinimmsoc.org

>  Subject: Re: [PAGID] oral Ig

>  

>   

>  

>  If one is a "believer" in enteric Ig (and I am not), consider 

> placement of

>  nasojejunal tube and pass this as far as one would need to bypass gastric

>  contents.  Not that protein digestion fails to occur in the small intestine,

>  however.

>  

>  Have you considered a trial of  Ivig (considering higher doses)?  

>  

>  Sincerely, 

>  Daniel H. Conway, MD 

>  Asst. Professor of Pediatrics 

>  St. Christopher's Hospital for Children 

>  Drexel University College of Medicine 

>  

>    _____  

>  

>  The information in this communication is confidential and is directed 

> only

>  to the intended recipient.  Please do not forward this communication 

> without

>  my permission.  If you have received this communication in error, please

>  notify me immediately and delete/destroy this communication.

>  

>  

>  

>  

>  

>    _____  

>  

>  From: yaejeankim at skku.edu

>  To: pagid at list.clinimmsoc.org

>  Date: Sat, 27 Jun 2009 19:45:56 +0900

>  Subject: [PAGID] oral Ig

>  

>  Hi, all 

>  

>   

>  

>  I have another question about a patients with WAS who got 

> transplanted and

>  has had chronic diarrhea due to virus called "calicivirus".

>  

>   

>  

>  This is a pt with WAS who was transplanted about a year ago. He developed

>  severe severe GVH including skin and gut. He got better...then he developed

>  severe diarrhea which was suspected for GVH back then and H-O guy put 

> him on

>  a significant immunosuppresion...later calicivirus was reported. He has 

> had

>  calicivirus dected for the past 7 months...still has diarrhea upto 8-10 

> times

>  a day. Multiple endoscopies...the most recent one showed no evidence of 

> GVH

>  but more likely viral enteritis...no CMV or EBV were seen on staining. 

> 

>  

>   

>  

>  I requested for EM...because I was expecting to see virus particle if 

> there is

>  any invasion... this is pending and takes long time...I am not sure 

> whether we

>  can identify calici by EM...anyway I though that was worth of try. 

>  

>   

>  

>  For tx options...there is nothing to give but the child is still 

> suffering a

>  lot. And finally, I have thought of oral IVIG ....giving Ig by mouth to

>  control the viral infection in the gut mucosa....there is no guarantee 

> that Ig

>  will be destroyed by gastric juice ...but I can still think and if that 

> is the

>  concern, I can persuade GI guy,  do the endoscopy and let him spary 

> Ig on

>  the surface of the gut.... Or Ig enema even!!

>  

>   

>  

>  Do you also try things like this with IVIG?  If I give Ig, how much (the

>  dose, and frequencies) should I give per mouth? 

>  

>  Thanks for any comments. 

>  

>   

>  

>  YaeJean Kim, MD

>  

>   

>  

>  Assistant Professor 

>  

>  50 Ilwon-dong Gangnam-gu

>  

>  Division of Infectious Diseases

>  

>  Department of Pediatrics

>  

>  Samsung Medical Center

>  

>  Sungkyunkwan University

>  

>  Seoul, 135-710

>  

>  South Korea

>  

>  tel) 82-2-3410-3539, 0987

>  

>  fax) 82-2-3410-0043

>  

>  yaejeankim at skku.edu

>  

>    _____  

>  

>  From: pagid-bounces at list.clinimmsoc.org

>  [ On Behalf Of Torgerson, Troy

>  Sent: Friday, June 26, 2009 8:21 AM

>  To: pagid at list.clinimmsoc.org

>  Subject: Re: [PAGID] two questions on enteritis

>  

>   

>  

>  YaeJean,

>  

>   

>  

>  IPEX is certainly a good initial thought given his symptoms but I would

>  include a couple of other disorders:

>  

>  First, for IPEX:  Has he had eczema or other rash?   Has he had other

>  autoimmunity as well (hemolytic anemia, thrombocytopenia, liver disease,

>  etc.)?  Most of the pts with FOXP3 mutations have other autoimmune

>  manifestations in addition to the enteropathy, eczema, and endocrinopathy.

>  Have you been able to get flow cytometry done to see if he has FOXP3+ 

> cells

>  in his CD4+ population, would also look at CD25 expression by flow to 

> make

>  sure it is there (see James' comment)?  When they sequenced FOXP3, do 

> you

>  know what they sequenced and how much of the gene they looked at?  

> About 5%

>  of the mutations we have identified are in non-coding regions of the 

> gene

>  (polyadenylation site or upstream non-coding region).  If they sequenced

>  genomic DNA did they look at all of the exon/intron junctions to rule 

> out a

>  splicing mutation or did they sequence cDNA?  

>  

>   

>  

>  Second, Leaky SCID:  Some Leaky SCID/Omenn or maternally engrafted SCID

>  patients can look a lot like IPEX.  Pts with IPEX can get infections 

> for

>  sure but pneumonias are not all that common and "frequent" infections 

> are

>  not all that common.  What are the T/B/NK numbers?  Are they his T/B/NK

>  cells or his mom's?  Do his T cells proliferate to mitogens/antigens? 

>  Do

>  you know whether his T cells are mostly CD45RA+ (naïve) or CD45RO+ (mature)?

>  - leaky SCID's & maternally engrafted SCID's are usually very skewed 

> to

>  CD45RO+.  Are his parents consanguineous? 

>  

>   

>  

>  Third, CGD:  Incidence of IBD/IBD-like symptoms is very high in CGD 

> and we

>  recently saw an infant here in Seattle with initial presentation of early

>  onset "Crohn's" disease with granulomatous lesions on biopsy that has 

> X-CGD.

>  Pneumonia also common in CGD.  Would check neutrophil oxidative burst 

> as

>  this would dramatically alter the therapeutic approach.

>  

>   

>  

>  Best,

>  

>   

>  

>  TT

>  

>   

>  

>  Troy R. Torgerson, MD PhD

>  

>   

>  

>  Assistant Professor, Pediatric Immunology/Rheumatology

>  

>  University of Washington, Department of Pediatrics

>  

>   

>  

>  Co-Director, Immunology Diagnostic Laboratory

>  

>  Center for Immunity and Immunotherapies

>  

>  Seattle Children's Research Institute

>  

>  1900 9th Ave., C9S-7

>  

>  Seattle, WA  98101-1305

>  

>   

>  

>  Tel:  (206) 987-7450

>  

>  Fax:  (206) 987-7310

>  

>   

>  

>  Email:  Troy.Torgerson at seattlechildrens.org

>  

>   

>  

>    _____  

>  

>  From: pagid-bounces at list.clinimmsoc.org

>  [ On Behalf Of YaeJean Kim

>  Sent: Thursday, June 25, 2009 2:46 PM

>  To: pagid at list.clinimmsoc.org

>  Subject: [PAGID] two questions on enteritis

>  

>   

>  

>  Dear all,

>  

>   

>  

>  I am YaeJean Kim who attended the 2007 PID summer school while I was 

> a

>  fellow in Seattle and now am relocated to Seoul, Korea. 

>  

>   

>  

>  I see a patient in my institute and have questions as below. 

>  

>   

>  

>  This is a now 18 month boy who is suspected for IPEX or IPEX like syndrome.

>  He has had intractable diarrhea, recurrent infections including pneumonia

>  and anal infection, fistula, hypothyroidism (only endocrinopathy

>  manifestiation he has) since age of 1 month. His brother died too with

>  similar features. 

>  

>   

>  

>  He was initially presented with failure to thrive. Intestinal biopsy 

> (at the

>  age of 7 mo) was suspected for IPEX but FOXP3 mutation was not observed.

>  Because of severe anal fistula, he received cecostomy. He is now on

>  azathioprine by our GI guy who is the main doctor for him. He still 

> seems to

>  have frequent infection with fevers and get hospitalized for 

> antibiotics. Do

>  you have any suggestions? Or should we repeat the test? All the tests 

> were

>  done about 10 months ago. 

>  

>   

>  

>  I would appreciate any feedback. Thanks a lot.  

>  

>   

>  

>   

>  

>  Jean

>  

>   

>  

>  --------------------------------------------

>  

>   

>  

>  YaeJean Kim, MD

>  

>   

>  

>  Assistant Professor 

>  

>  50 Ilwon-dong Gangnam-gu

>  

>  Division of Infectious Diseases

>  

>  Department of Pediatrics

>  

>  Samsung Medical Center

>  

>  Sunggyungwan University

>  

>  Seoul, 135-710

>  

>  South Korea

>  

>  tel) 82-2-3410-3539, 0987

>  

>  fax) 82-2-3410-0043

>  

>  yaejeankim at skku.edu

>  

>   

>  

>  Children's Hospital and Regional Medical Center is now Seattle Children's.

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