This document discusses the use of intravenous immunoglobulin (IVIg) for various autoimmune diseases and cancer. It provides details on:
- How IVIg is prepared from blood donations and its definitive preparation process.
- Its clinical applications in treating severe immune deficiency diseases and various autoimmune conditions.
- Studies showing IVIg's effectiveness in treating autoimmune conditions like ITP, SLE, and experimental models of SLE.
- Mechanisms by which IVIg may exert anti-cancer effects like inhibiting tumor cell proliferation, invasion, and metastases in various cancer cell lines and mouse models. It also discusses a case report of a patient achieving remission of thymoma after IVIg treatment
By Dr. Usama Ragab Youssif
Definitions & Nomenclatures
Structure of immunoglobulins
Immunoglobulins in our bodies
Physiologic actions of immunoglobulins
The Idea behind use of immunoglobulins
Uses: indications, mechanisms, preparation, posology, administration
Adverse effects
Safe practice
Final bottom-line
Intravenous Immunoglobulin (IVIG) is a solution of highly purified immunoglobulin G, derived from large pools of human plasma that contains antibodies against a broad spectrum of bacterial and viral agents.
IVIG can be given safely in the convenience of your home. It can be given either intravenously (IV through the veins) or subcutaneously (under the skin).
NBN Infusions will send a nurse with all necessary supplies to complete your infusion, in the comfort of your own home.
NBN Infusions will even help you and your doctor complete all necessary documents. Our goal is to make the process as easy as possible so you can focus on getting the treatment that you need.
Insurance companies can be challenging to deal with in the IVIG treatment approval process sometimes. So, NBN Infusions will help you deal with your insurance process so that you can get approved for your IVIG treatments in a timely manner.
What Does IVIG Treat?
IVIG Therapy has been used extensively in the treatment and prevention of a variety of infectious and inflammatory diseases. Patients with compromised Immune systems who have these conditions often benefit from the passive immunity provided by IVIG therapy.
IVIG is used in patients with primary immunodeficiencies and certain conditions associated with B-cell Chronic Lymphocytic Leukemia, Pediatric HIV, and Bone Marrow Transplant. IVIG is also utilized to raise platelet counts in patients with Idiopathic Thrombocytopenic Purpura and to treat the symptoms related to other clinical conditions such as Kawasaki Syndrome.
Various other diseases and immune disorders where IVIG is used include:
Chronic Sinusitis
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Multiple Sclerosis (MS)
Myasthenia Gravis(MG)
Systenic Lupus Erythematosus (SLE)
Guillain-Barre Syndrome (GBS)
Autoimmune Diabetic Neuropathy
Polymyositis
Multifocal Motor Neuropathy (MMN)
Dermatomyositis
Rheumatoid Arthritis (RA)
Common Variable Immunodeficiency (CVID)
Hypogammaglobulinemia
Severe Combined Immunodeficiency (SCID)
Wiskott-Aldrich Syndrome (WAS)
X-Linked Agammaglobulinemia (XLA)
other connective tissue disorders
By Dr. Usama Ragab Youssif
Definitions & Nomenclatures
Structure of immunoglobulins
Immunoglobulins in our bodies
Physiologic actions of immunoglobulins
The Idea behind use of immunoglobulins
Uses: indications, mechanisms, preparation, posology, administration
Adverse effects
Safe practice
Final bottom-line
Intravenous Immunoglobulin (IVIG) is a solution of highly purified immunoglobulin G, derived from large pools of human plasma that contains antibodies against a broad spectrum of bacterial and viral agents.
IVIG can be given safely in the convenience of your home. It can be given either intravenously (IV through the veins) or subcutaneously (under the skin).
NBN Infusions will send a nurse with all necessary supplies to complete your infusion, in the comfort of your own home.
NBN Infusions will even help you and your doctor complete all necessary documents. Our goal is to make the process as easy as possible so you can focus on getting the treatment that you need.
Insurance companies can be challenging to deal with in the IVIG treatment approval process sometimes. So, NBN Infusions will help you deal with your insurance process so that you can get approved for your IVIG treatments in a timely manner.
What Does IVIG Treat?
IVIG Therapy has been used extensively in the treatment and prevention of a variety of infectious and inflammatory diseases. Patients with compromised Immune systems who have these conditions often benefit from the passive immunity provided by IVIG therapy.
IVIG is used in patients with primary immunodeficiencies and certain conditions associated with B-cell Chronic Lymphocytic Leukemia, Pediatric HIV, and Bone Marrow Transplant. IVIG is also utilized to raise platelet counts in patients with Idiopathic Thrombocytopenic Purpura and to treat the symptoms related to other clinical conditions such as Kawasaki Syndrome.
Various other diseases and immune disorders where IVIG is used include:
Chronic Sinusitis
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Multiple Sclerosis (MS)
Myasthenia Gravis(MG)
Systenic Lupus Erythematosus (SLE)
Guillain-Barre Syndrome (GBS)
Autoimmune Diabetic Neuropathy
Polymyositis
Multifocal Motor Neuropathy (MMN)
Dermatomyositis
Rheumatoid Arthritis (RA)
Common Variable Immunodeficiency (CVID)
Hypogammaglobulinemia
Severe Combined Immunodeficiency (SCID)
Wiskott-Aldrich Syndrome (WAS)
X-Linked Agammaglobulinemia (XLA)
other connective tissue disorders
Isocitrate dehydrogenase mutations in hereditary diseaesamalreffat
NADPH production, which is vital for protecting cells from oxidative stress, depends on IDH enzyme.
If there is any mutation in this enzyme , it will adversely affects the cell.
Progretion of tumors and other diseases occurs consecutively.
Autoimmune endocrinopathies
Prof. Khaled el Hadidy, UEDA, Beni-Suef University
First Lupus day 16 October 2018 immunology unit, faculty of medicine, Beni-Suef University
Isocitrate dehydrogenase mutations in hereditary diseaesamalreffat
NADPH production, which is vital for protecting cells from oxidative stress, depends on IDH enzyme.
If there is any mutation in this enzyme , it will adversely affects the cell.
Progretion of tumors and other diseases occurs consecutively.
Autoimmune endocrinopathies
Prof. Khaled el Hadidy, UEDA, Beni-Suef University
First Lupus day 16 October 2018 immunology unit, faculty of medicine, Beni-Suef University
H. Zheng - Innate immune evasion by foot-and-mouth disease virus EuFMD
Session III
The innate immunity represents an early innate host antiviral defense mechanism that takes place shortly after virus invasion and long before the development of adaptive immunity. Viruses must outcompete or subvert the initial antiviral innate immune response, allowing the establishment of persistent replication that leads to continuous stimulation of both the innate and adaptive immune components. Similar to other viruses, foot-and-mouth disease virus (FMDV), an etiological agent of severe and highly contagious viral disease, is reported to have evolved multiple strategies to evade and attenuate the host innate immunity to facilitate viral replication. In our lab, based on a subset of luciferase assays using promoter constructs of key components of the innate immunity coupled with IP-MS and Y2H, we decipher the mode of action of how viral proteins interact with host factors and further disrupt the host factor-mediated innate immunity, especially in the context of the type I interferon (IFN) system.
Report on Rabies vaccine in India. Rabies is caused by lyssavirus which is a deadly virus which affects the CNS. And its genetic material consists of mainly RNA and it undergoes reverse transcription mechanism and multiply in the host.
Glaucoma is a group of ocular diseases marked with elevated intraocular pressure IOP, reduced visual acuity, optic neuropathies and the corresponding visual field
defects. Its etiology is unknown. The aim of this study was to assess Helicobacter pylori bacteria in glaucoma disease patients. The infection of H. pylori was
associated with glaucoma by detecting serum IgG antibody against H. pylori qualitatively using immunochromatographic method; and also by isolating the organism
from media cultures of fresh faecal samples of the glaucoma patients. In a total of 217 glaucoma patients, 212 (97.7%) were IgG serum positive; while only 25
(13.89%) of the 180 control was IgG positive P<.001. H. pylori was successfully cultured in 202 (95.3%) feacal samples of these 212 seropositives. The 202 isolates
were all Gram negative and produced the enzymes catalase, oxidase and urease. They were highly motile; and poor in the hydrolysis of indoxyl acetate and hippurate
(4.9% and 4.4% respectively). They poorly fermented sugar, 7.4% for sucrose and glaucose and 12.3% for lactose. In the antibiotics susceptibility pattern, H. pylori
was most resistant to vancomycin 66.8% (135 of the 202) and metronidazole 44.5% (90 of the 202); while H. pylori was most sensitive to tetracycline and
ciprofloxacin by 94% and 91.5% respectively. The biochemical characteristics and the antibiotics resistant marker for claritromycin are chromosomal while the
resistant marker for amoxicillin was plasmid located. In conclusion, H. pylori infection is associated with the risk for glaucoma development in the population.
Clinicians who care for patients with H. pylori infection should also consider that H. pylori can cause not only digestive illness but also eye disease. This association
offers a novel approach towards the care for glaucoma, the second leading cause of blindness.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
1. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Yehuda Shoenfeld
MD,FRCP,
IVIG;The myth and realityIVIG;The myth and reality
IVIG
CONPO Barcelona2013
Harnessing the innate immunity to
modulate autoimmunity and cancer
3. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Definitive way of preparation; produced by 25Definitive way of preparation; produced by 25
pharmaceutical companies (very expensive).pharmaceutical companies (very expensive).
Clinical applications: treatment of severe immuneClinical applications: treatment of severe immune
deficiency diseases and a variety of autoimmunedeficiency diseases and a variety of autoimmune
conditions.conditions.
Pooled IgG (immunologlobulin G) from 6,000Pooled IgG (immunologlobulin G) from 6,000--20,00020,000
blood donation.blood donation.
4. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Intravenous Immunoglobulin-IVIg
Pooled IgG (immunologlobulin G) from 6,000-
20,000 blood donation (representing the Innate Immune
repertoire)
Definitive way of preparation; produced by 25
pharmaceutical companies (very expensive)
Clinical applications: Treatment of severe
immune deficiency diseases and a variety of
autoimmune conditions
9. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Immune thrombocytopenia (ITP)
ITP is an
autoimmune
disease due to
autoantibody
to endogenous
platelets
Causes platelet
destruction by
macrophages
and bleeding
12. Yehuda Shoenfeld, MD,FRCP ( Hon.)
A study of 20 SLE patients withA study of 20 SLE patients with
intravenous immunoglobulinintravenous immunoglobulin
clinical and serologic responseclinical and serologic response
Yair Levy, Yaniv Sherer, Alaa Ahmed, Pnina Langevitz, Jacob GeorYair Levy, Yaniv Sherer, Alaa Ahmed, Pnina Langevitz, Jacob George,ge,
Fabizio Fabbrizzi, Jeff Terryberry, Martyna Meissner, Margalit LFabizio Fabbrizzi, Jeff Terryberry, Martyna Meissner, Margalit Lorber,orber,
James B Peter,James B Peter, Yehuda Shoenfeld.Yehuda Shoenfeld.
Lupus 8, 705Lupus 8, 705--712, 1999712, 1999
A beneficial clinical response following
IVIg treatment was noted in 17 out of
20 patients (85%).
Some clinical manifestations responded
more to treatment: arthritis, fever,
thrombocytopenia, and neuropsychiatric
lupus.
13. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Successful treatment of early secondarySuccessful treatment of early secondary
myelofibrosismyelofibrosis
in SLE with IVIG.in SLE with IVIG.
Aharon A, Levy Y, Bar Dayan Y, Afek A, Zandman-Goddard, Skurnik
Y, Fabrrizzi F, Shoenfeld Y
Lupus 6: 408-411,1997.
IVIG
14. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Reduced proteinuria followingReduced proteinuria following
repeated courses of IVIGrepeated courses of IVIG
0
2
4
6
8
2m
on
bf1m
on
bf1stcycle
2nd
cycle3rd
cycle4th
cycle5th
cycle6cycle
12m
on
af
18m
on
af
30m
on
af
Urinaryprotein
extraction(g/24h)
15. Yehuda Shoenfeld, MD,FRCP ( Hon.)
A Comparison Between Prednisone DosesA Comparison Between Prednisone Doses
used for the Treatment of SLE Patientsused for the Treatment of SLE Patients
Before and After IVIgBefore and After IVIg
0
10
20
30
40
50
60
BeforeIVIG After6cyclesofIVIG
P<0.05P<0.05
16. Yehuda Shoenfeld, MD,FRCP ( Hon.)
2. Anti2. Anti--idiotypicidiotypic AbsAbs
Anti-Id Ab
Pathogenic auto-
Ab
Anti-Id Abs modulates the immune system by suppressing
auto-Abs production
17. Yehuda Shoenfeld, MD,FRCP ( Hon.)
AIM :
To evaluate theTo evaluate the
efficacy of theefficacy of the
antianti--dsDNA antidsDNA anti--idiotypesidiotypes
enrichedenriched IVIGIVIG
19. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Affinity purification of antiAffinity purification of anti--dsDNAdsDNA
antianti--ID from IVIGID from IVIG
Anti-dsDNA-Sepharose
Loading dialyzed
IVIG
YY
YY
YY
YY
YY
YY
YYYY
YYYY
YY
YY
Elution with
HCl-glycine
16 hours at 4oC
YYYYYY
YYYYYY
YYYY
YY
antianti--dsDNA antidsDNA anti--IDID
YY
YY
YY
YY
YY
YY
20. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Treatment of NZB/W F1 mice
with IVIG-ID
Three weekly injections to the tail vein
of NZB/W F1 mice:
IVIG-ID : 2 mg/kg = 60 µg/mouse
IVIG: 400 mg/kg = 12 mg/mouse
21. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Proteinuria in NZB/W F1 miceProteinuria in NZB/W F1 mice
treated with SUPERIVIG and IVIGtreated with SUPERIVIG and IVIG
0
5
10
15
20
25
30
IVIG-ID IVIG CONTROL
G/L
*
22. Yehuda Shoenfeld, MD,FRCP ( Hon.)
IVIG-IDIVIG-ID IVIGIVIG NON-TREATEDNON-TREATED
Prevention of mesangial mouse IgG
deposits in NZB/W F1 mice
treated (early treatment) with:
Prevention of mesangial mouse IgGPrevention of mesangial mouse IgG
deposits in NZB/W F1 micedeposits in NZB/W F1 mice
treated (early treatment) with:treated (early treatment) with:
23. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Cumulative number of deaths withCumulative number of deaths with
concomitant proteinuria in NZB/W F1 miceconcomitant proteinuria in NZB/W F1 mice
Weeks of ageWeeks of age
25 30 35 40 45
0
2
4
6
8
10
12
IVIGIVIG--IDID
IVIGIVIG
ControlControl
NumberofdeathsNumberofdeaths
24. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Efficacy of IVIG affinityEfficacy of IVIG affinity--purified antipurified anti--
doubledouble--stranded DNA antistranded DNA anti--idiotypicidiotypic
antibodies in the treatment of anantibodies in the treatment of an
experimental murine model ofexperimental murine model of
systemic lupus erythematosus.systemic lupus erythematosus.
Shoenfeld Y,Shoenfeld Y, Rauova L, Gilburd BRauova L, Gilburd B, Kvapil F,, Kvapil F,
Goldberg I, Kopolovic J, Rovensky J,Goldberg I, Kopolovic J, Rovensky J, Blank M.Blank M.
Int Immunol. 2002 ;14:1303Int Immunol. 2002 ;14:1303--1111
25. Yehuda Shoenfeld, MD,FRCP ( Hon.)
YY
YY
YY
YY
YY
YY
YY
YY
AntiAnti-- dsDNAdsDNA
SLESLE
YY
YY
YY
YY
YY
YY
YY
YY
AntiAnti--2GPI2GPI
AntiphospholipdAntiphospholipd
syndromesyndrome
Myasthenia
Myasthenia
GravisGravis
YY
YY
YYYY
YY
YY
YY
YY
AntiAnti-- AChRAChR
Autoimmune Disease Specific IVIg:Autoimmune Disease Specific IVIg:
Low Dose, High EfficacyLow Dose, High Efficacy
Special types of IVIg for autoimmune diseases
Pemphigus
Pemphigusvulgaris
vulgaris
YY
YY
YY
YY
YYYY
YY
YY
Anti
Anti--desmoglein
desmoglein1/31/3
26. Yehuda Shoenfeld, MD,FRCP ( Hon.)
IVIG Treatment of Cancer
Y. Shoenfeld, Sheba Medical Center, Israel
27. Reactivity of the human IVIG with a panel of
human cell line
Human bladder carcinoma cell line T24, human glioma cell line U-138MG, human
head-and-neck cancer cell line PCI-13, human lymphoid cell line LG2 and human
melanoma cell lines 501, 553B, 836,1379, Colo38 and Mel-1386 at 4oC for 2 hours.
Reactivity of the humanized antibody IVIG with a panel of cell lines
0
1
2
T2 4 8 3 6 C o lo 3 8 M el-13 8 6 DAM -
M B -2 3 1
553 B 2 9 3 /KDR 13 79 PC I-13 LG2 50 1 U-13 8 M G
Cell lines
ODat450nm
IV IG
control
28. Yehuda Shoenfeld, MD,FRCP ( Hon.)
IVIg: Prevention of Melanoma
Metastases
Gamma-globulin inhibits tumor spread in mice
Yehuda Shoenfeld and Pnina Fishman
International immunology
11: 1247 - 1251, 1999
29. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Effect of IVIg (I.V.) on the Development of
Melanoma Metastases
6 IVIG - Presentation, Oct 95
0
25
50
75
100
125
No.offoci
(%ofcontrol)
Control 0 0,4 0,4,9
DAYS OF IVIG TREATMENT
P<0.001 P<0.001 P<0.001
30. Yehuda Shoenfeld, MD,FRCP ( Hon.)
IVIg Prolongs the Survival of Tumor
Bearing Mice
0
20
40
60
80
100
0 20 40 60 80 100
Days after amputation
%survival
Treated
Control
a - Sarcoma
0
20
40
60
80
100
0 20 40 60 80 100
Days after amputation
%survival
Treated
Control
b - Melanoma
Sarcoma Melanoma
33. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Inhibitory effect of IVIg on in vitro CT26 cellInhibitory effect of IVIg on in vitro CT26 cell
proliferationproliferation
* p < 0.05
** p < 0.01
*** p < 0.001
0
10
20
30
40
50
60
70
80
1 5 15 40
IVIg concentration (mg/ml)
%ofinhibition
24h
48h
72h
**
***
*
**
**
*
Time course and dose responseTime course and dose response
34. Yehuda Shoenfeld, MD,FRCP ( Hon.)
•Matrigel resultsEffect of IVIg on CT26 cell invasiveness
The invasive capacity of CT26 cells was decreased by IVIgThe invasive capacity of CT26 cells was decreased by IVIg
(time(time-- and doseand dose--dependent effect)dependent effect)
39.70
0
10
20
30
40
50
60
48h 72h
%ofinhibitionofinvasion
IVIg 20mg/ml
IVIg 40mg/ml
p < 0.001
35. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Dose Dependent Effect of IVIg on the Proliferation of
Human Colon Carcinoma, HCT-116 Cells
0
20
40
60
25 10 5 2.5 1.25
IVIg Concentration (mg/ml) .
[H
3
]Thymidineincorporation
(%ofinhibition)
36. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Shrinkage of Melanoma Metastases Following High dose
Intravenous Immunoglobulin Treatment
Shoenfeld Y, Levy Y, Fishman P.
IMAJ 3; 698-699, 2001
Human Experience
37. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Total remission of thymus
carcinoma after treatment with
intravenous immunoglobulin
MurieMurie--Fernandez M, et al. Clin Transl Oncol. 2006; 8: 697Fernandez M, et al. Clin Transl Oncol. 2006; 8: 697--99
42 year-old woman with myasthenia gravis
associated with a malignant thymoma.
A complete remission of the thymoma was
confirmed by FDG-PET after four cycles of
immunoglobulins.
38. IVIg as a natural anti
cancer agent
Mechanisms
40. Yehuda Shoenfeld, MD,FRCP ( Hon.)
IVIGIVIG Inhibits MMPInhibits MMP--9 mRNA9 mRNA expression inexpression in
mouse Melanoma cellsmouse Melanoma cells
0
0.5
1
1.5
MMP-9mRNA
IVIG (mg/ml)663300
2.8 kbMMP-9
G3PDH 1.4 kb
IVIG concentration
Shapiro S, Shoenfeld Y, Gilburd B, Sobel E, Lahat N. Intravenous gamma globulin inhibits the
production of matrix metalloproteinase-9 in macrophages. Cancer. 2002, 95: 2032 – 2037.
41. ANTI-VEGF ACTIVITY OF IVIg
IVIGIVIG
IVIg as an anti-angiogenic agent ?IVIg as an antiIVIg as an anti--angiogenic agent ?angiogenic agent ?
42. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Binding of IVIg to the recombinant VEGF
Anti-VEGF activity in an IVIg preparation
(ELISA)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0.0 0.4 0.8 1.6 3.1 6.3 12.5 25.0 50.0
IVIg concentration (mg/ml)
Absorbance(450nm)
Anti-VEGF activity in an IVIg preparation
(ELISA)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0.0 0.4 0.8 1.6 3.1 6.3 12.5 25.0 50.0
IVIg concentration (mg/ml)
Absorbance(450nm)
Anti-VEGF activity in an IVIg preparation
(ELISA)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0.0 0.4 0.8 1.6 3.1 6.3 12.5 25.0 50.0
IVIg concentration (mg/ml)
Absorbance(450nm)
2000 2
38 kD
IVIg (µg/ml)
VEGF samples were loaded onto 12%
SDS-PAGE and blotted on to
nitrocellulose membranes
43. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Competition of MAV and IVIg for
binding to the VEGF in an immunoblot
••g/ml)µ(10incubated with MAV-pre(2mg/ml) to the VEGFIVIgIVIgBinding ofLane 1:Lane 1:
••(2mg/ml)incubated with IVIg-preg/ml) to the VEGFµ(10MAVMAVBinding ofLane 2:Lane 2:
••(2mg/ml) to the VEGFIVIgIVIgofDirect bindingLane 3:Lane 3:
••g/ml) to the VEGFµ(10MAVMAVofDirect bindingLane 4.Lane 4.
1 2 3 4
44. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Injection of bFGF
VEGF
IVIG as an anti VEGF-
Arei Solomon @Y Shoenfled
46. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Anti-VEGF activity of IVIg in vivo
IVIG inhibits VEGF- induced blood
perfusion in mouse hind-limb ischemia
0.40
0.50
0.60
0.70
0.80
0.90
1.00
1.10
T0 T7 T14 T21
Days post surgery
Perfusionratio
without VEGF
with VEGF
with VEGF + IVIg
IVIG inhibits VEGF- induced blood
perfusion in mouse hind-limb ischemia
0.40
0.50
0.60
0.70
0.80
0.90
1.00
1.10
T0 T7 T14 T21
Days post surgery
Perfusionratio
without VEGF
with VEGF
with VEGF + IVIg
Blood flow recorded by LaserBlood flow recorded by Laser
Doppler Perfusion ImagingDoppler Perfusion Imaging
47. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Control IVIg treated
A rich vascular bed and the
growing tumor mass.
Complete eradication of tumor
mass.
Corneal insemination of CT26 colon carcinoma cells
Effect of IVIg on colon carcinomaEffect of IVIg on colon carcinoma
primary tumor growing potentialprimary tumor growing potential
After10 daysAfter10 days
Damianovich M, Solomon A S, Blank M, Shoenfeld Y. Ann N Y Acad Sci 2007; 1110:567–577
48. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Mechanisms for IVIg as Anti-
metastatic Agent
Increased secretion of Il-12
Increased activity of NK
Induction of apoptosis in tumor cells
Direct binding - cytostatic (cytotoxic)?
- c’ dependent?
Anti-MMP-9,Cathepsin D
Anti –VEGF
Anti –Blyss ( BAFF)
49. Yehuda Shoenfeld, MD,FRCP ( Hon.)
Conclusions
GammaGamma--globulins from anglobulins from an IVIgIVIg preparationpreparation
contain a subcontain a sub--fraction offraction of antianti--VEGF AbsVEGF Abs with awith a
possible antipossible anti--angiogenicangiogenic activityactivity
VEGF specific activity of IVIg mayVEGF specific activity of IVIg may suggestsuggest
by which IVIg may suppressby which IVIg may suppressa new action mechanisma new action mechanism
autoimmune diseasesautoimmune diseasesand someand somecancer
IVIgIVIg
51. Yehuda Shoenfeld, MD,FRCP ( Hon.)
BAFF, a New Target for IntravenousBAFF, a New Target for Intravenous
Immunoglobulin in Autoimmunity andImmunoglobulin in Autoimmunity and
CancerCancer
Le Pottier L, Bendaoud B, Dueymes M, Daridon C, Youinou P, ShoenLe Pottier L, Bendaoud B, Dueymes M, Daridon C, Youinou P, Shoenfeld Y,feld Y,
Pers JO.Pers JO. J Clin Immunol. 2007J Clin Immunol. 2007
The excess in serum level and/or tissue production of BAFF in:
SLE (Zhang J, et al. Cutting edge: A role for B lymphocyte stimulator in systemic
lupus erythematosus. J Immunol 2001; 166: 6–10)
SSc (Matsushita T, et al. Elevated serum BAFF levels in patients with systemic
sclerosis: Enhanced BAFF signaling in systemic sclerosis B lymphocytes. Arthritis
Rheum 2006; 54: 192–201)
MS(Thangarajh M, et al. Expression of B-cell-activating factor of the TNF family
(BAFF) and its receptors in multiple sclerosis. J Neuroimmunol 2004; 152:183–190)
B-CLL (Novak AJ, et al. Aberrant expression of B lymphocyte stimulator by B
chronic lymphocytic leukemia cells: A mechanism for survival. Blood 2002; 100:
2973–2979)
52. Yehuda Shoenfeld, MD,FRCP ( Hon.)
BAFF, a new target for intravenous
immunoglobulin in autoimmunity and
cancer.
Le Pottier L, Bendaoud B, Dueymes M, Daridon C, Youinou P,Le Pottier L, Bendaoud B, Dueymes M, Daridon C, Youinou P,
Shoenfeld Y, Pers JO. J Clin Immunol. 2007 ;27 : 257Shoenfeld Y, Pers JO. J Clin Immunol. 2007 ;27 : 257--265265
Nonglycosylated recombinant BAFF,
glycosylated affinity-purified BAFF, and
recombinant APRIL (but not TNFalpha), were
recognized by certain IgG in IVIg, and their
F(ab')(2) fragments.
The presence of anti-BAFF and anti-APRIL Abs
in IVIg.
53. IVIG as Anti BLISS ( BAFF)
(Functional)
J Clin Immunol 2007
55. Yehuda Shoenfeld, MD,FRCP ( Hon.)
ADVERSE EFFECTS AND VIRAL SAFETY OF
INTRAVENOUS IMMUNOGLOBULIN THERAPY
IN 56 PATIENTS WITH AUTOIMMUNE
DISEASES
Yaniv Sherer, Yair Levy, Pnina Langevitz, Fabrizio
Fabbrizzi, Yehuda Shoenfeld
Department of Medicine ‘B’ and Center of Autoimmune Diseases, Sheba
Medical Center, Tel-Hashomer, and Sackler Faculty of Medicine, Tel-Aviv
University, Israel
Pharmacology 2001; 62: 133-137
56. Yehuda Shoenfeld, MD,FRCP ( Hon.)
CONCLUSIONS:
IVIg- the myth and reality
IVIG is effective in
autoimmune conditions –multiple
mechanisms
IVIg anti -cancer effects in;
melanoma, carcinoma, sarcoma and
lymphoma
IVIG representing the innate
immune system affect tumors by
diverse mechanisms
IVIG
Gallileo
Einstein
57. Five Jews change the
way we see the world:
Moses: ‘’the Law is everything.’’
Jesus: ‘’Love is everything.’’
Marx: ‘’Money is everything.’’
Freud: ‘’Sex is everything.’’
Einstein: ‘’Everything is relative.’’