Immunologist and
geneticist Ray D. Owen, professor of biology, emeritus, at Caltech passed away
on September 21. Owen's most significant contribution to immunology was his
1945 discovery of immunological tolerance in fraternal twin cattle. Using blood
typing, he discovered that each twin had no immune response to the foreign
antigens introduced from the other twin. His findings paved the way for the
experimental induction of tolerance through immune suppression and for early
tissue grafting—which initiated the era of organ transplantation. Owen's later
work included studies on human antibodies, blood-group antigens, the evolution
of immune systems, and the genetic analysis of the major histocompatibility
complex—a large family of genes that plays an important role in the immune
system and autoimmunity. Dr. Owen received his PhD in genetics from the
University of Wisconsin and became an associate professor at Caltech in 1947;
where he was promoted to full professor in 1953 and became professor emeritus
in 1983. Not only was Owen a brilliant scientist, he was highly recognized for
his extraordinary dedication to mentorship at Caltech, where he launched the
effort to admit female undergraduate students; which ultimately allowed the
first female undergraduates to enroll at the Institute in 1970. His accomplishments
led Leonore Herzenberg, professor of genetics at the Stanford School of
Medicine and pioneer of immunology, to write "Dr. Owen's belief in the
genderlessness and color-blindness of intelligence and creativity has
encouraged men and women to excel in their chosen fields," in a letter
recommending Owen for a lifetime mentoring award.
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Wednesday, October 22, 2014
Thursday, January 23, 2014
Sadly, gastroenterologist and immunologist Lloyd Mayer M. D., Head of the Division of Clinical Immunology, Icahn School of medicine at Mount Sinai, passed away September 5, 2013. Dr. Mayer was a highly esteemed colleague of the mucosal immunology community who made major contributions in the field. His passion was inflammatory bowel disease and among many scientific contributions he discovered that T cells secrete factors which control the class switching, activation, and proliferation of B cells. He applied himself to numerous organizations and held the highly esteemed position of Chairman of the National Scientific Advisory Committee of the Crohn's and Colitis Foundation of America. He was highly active in the Allergy/Immunology community as his research focused on mechanisms of oral tolerance and he was a key member of the NIH NIAID Consortium of Food Allergy Researchers (CoFAR). Anyone who knew Dr. Mayer describe him as a selfless person who despite all of his extraordinary accomplishments always remained humble and unassuming and was an irreplaceable friend to anyone who knew him. For more details about his life and accomplishments, please view this memorial in the Journal of Clinical Immunology (published by Springer, Nov. 2013)
Friday, December 27, 2013
The New Year is approaching, bringing huge changes in healthcare coverage for most Americans. This recent focus on healthcare costs has highlighted the extreme financial burden of rare diseases; effective therapies may have been developed, but the cost of R & D to the pharmaceutical companies is huge, compared to the number of potential users. Take Hereditary Angioedema; billions of dollars were spent on development of a very effective therapy, 95% of which was spent on unsuccessful drug trials. To recoup this investment, patent rights prevent generic alternatives, and the cost is passed on to the some 1 in 50,000. Each patient spends upwards of $100,000 per year to manage their condition. Perhaps this shake-up will force administrators to examine the real cost of healthcare, from pre-clinical trials to approval.
Tuesday, December 3, 2013
In recognition of an innovator in immunology: Leonard Herzenberg, inventor of the FACS machine.
Immunologist,
geneticist, and philanthropist Dr. Leonard Herzenberg profoundly changed cell
biology and immunology with the invention of the fluorescence-activated cell sorter (FACS ) machine. Herzenberg created the
biotechnology in 1970, driven by the need for quantification of cell types
during his novel work with hybridomas, which are monoclonal antibody producing
B cells fused with cancer cells. The
FACS, also referred to as a flow cytometer, allows scientists to sort,
quantify, and identify different cells types, and has been vital to the field
ever since its existence. Not only did
his seminal biotechnology and research significantly advance what is known
about lymphocyte biology, he used the royalties from the FACS to further fund
his own research. Dr. Herzenberg’s ground
breaking achievements earned him an array of awards, most notably the Kyoto
Prize, a Japanese equivalent to the Nobel Prize. His priceless contributions will
continue to impact basic science research indefinitely.
Leonard Herzenberg (November 5, 1931 – October 27, 2013)
Tuesday, November 19, 2013
Claritin advertisements cause a placebo effect
It is well known that beliefs about the quality of a drug
can enhance its physiological effect, but little is known of the impact of
advertising of a branded drug. Kamenica et al (PNAS August 2013) conducted a clinical
trial to measure the physiological impact of direct-to-consumer advertising of the
antihistamine Claritin. The authors exposed subjects with or without allergies to
a skin test of common allergens, and then subjects received Claritin, and viewed
advertisements for Claritin or Zyrtec. Regardless
of allergy, all subjects experienced a wheal reaction to the skin test. In the
allergy subpopulation, there was no significant change in beliefs associated
with exposure to Claritin advertisements; however, in the subpopulation without
allergies, exposure to Claritin advertisements increased the efficacy of
Claritin (16% at 120 minutes). This
result suggests that advertising can have strong psychologically mediated
physiological effects to a drug.
It is unclear if the
results were due to the positive effect of Claritin ads or a negative effect of
Zyrtec ads. A small pilot test included
a group that did not receive advertisements, but the authors did not replicate
this arm in the larger study. A follow
–up trial should be conducted to determine if positive or negative
advertisements have a greater effect as well as a no advertisement control
group.
The association of anaphylaxis and chronic pulmonary diseases on hospital outcomes
Mulla et al (BMJ open
2013) sought to determine if chronic pulmonary diseases such as asthma, chronic
obstructive pulmonary disease (COPD),
and cystic fibrosis adversely impacted outcomes in hospitalized patients with various allergic
conditions including anaphylaxis. The
authors used data collected from a statewide hospital discharge database, of
which 2410 individuals had anaphylaxis. Asthmatics were found to have more than
twice the odds of receiving mechanical ventilation and sufferers of chronic
bronchitis and COPD had a prolonged hospitalization stay. The unique analysis of a large database
allowed the authors to determine that chronic pulmonary diseases increased the
risk of adverse outcomes among hospitalized patients with anaphylaxis.
The authors did not
have access to the complete medical records of the patients, how could this
have affected outcomes?
Could there be
anaphylaxis coding inconsistencies in hospital databases especially in patients
with pulmonary disease?
Monday, April 22, 2013
World Primary Immunodeficiencies Week 2013
The week of April 22-29, 2013 is World Primary Immunodeficiencies Week. We are pleased to present the following editorial, submitted by Drs.
Ricardo Sorensen, Amos Etzioni, Ahmed Bousfiha, and John Zeiger, on behalf of the World Primary
Immunodeficiencies Week Steering Committee:
Ricardo Sorensen M.D.,1 Amos Etzioni, M.D.,2 Ahmed Aziz Bousfiha , M.D.,3 John B. Zeiger, M.D.4
1. Department of Paediatrics Children's Hospital, 200 Henry Clay Ave. New Orleans, LA, USA
2. Meyer Children's Hospital, Haifa, Israel
3. Clinical Immunology Unit, King Hassan II University, Averroes Hospital, Casablanca, Morocco
4. Sydney Children’s Hospital, Randwick, New South Wales, Australia
Ricardo Sorensen M.D.,1 Amos Etzioni, M.D.,2 Ahmed Aziz Bousfiha , M.D.,3 John B. Zeiger, M.D.4
1. Department of Paediatrics Children's Hospital, 200 Henry Clay Ave. New Orleans, LA, USA
2. Meyer Children's Hospital, Haifa, Israel
3. Clinical Immunology Unit, King Hassan II University, Averroes Hospital, Casablanca, Morocco
4. Sydney Children’s Hospital, Randwick, New South Wales, Australia
Introduction
World Primary Immunodeficiency
Week (WPIW) 2013 runs from 22–29th April (www.worldpiweek.org). As this celebration and
awareness campaign approaches, it is time to reflect on progress made and the
challenges that remain for the primary immunodeficiency diseases (PID)
community. In this article, representatives from leading PID societies evaluate
the situation and plans for further progress in their respective areas of the
world. It is hoped that this situation analysis will prompt further focus and
enhanced collaboration on the gaps that remain in the pursuit of promoting
early diagnosis and treatment of PIDs.
Europe
The European Society for Primary
Immunodeficiency (ESID) is the oldest and largest professional organization
focused on PIDs. Currently ESID has 800 members and almost 2000 individuals
attended its last biennial meeting (Florence, October 2012).
ESID developed the first
clinical database for PIDs. Containing data from over 10,000 patients, this
large registry has been used for many important projects and published studies
(1-3). Furthermore, in 2012, ESID members collaborated in the publication of an
updated PID diagnostic protocol for non-immunologists. This protocol
incorporates newly defined PIDs and is designed to assist physicians caring for
adults and children to promptly and cost-effectively screen and diagnose PIDs
based on the clinical presentation and laboratory tests, with definitive tests
subsequently performed in partnership with specialist immunologists (4).
Aside from organizing the
biennial meeting, ESID is involved in many other educational activities, such
as a summer school for PID. A major objective of the organization is to
increase awareness of PID through a new website and meetings with patient
organizations. ESID also supports the wonderful ‘J project’, conducted by Prof.
László Maródi (Hungary), which aims to develop PID awareness and expertise in
eastern and central European countries (5).
In the upcoming year, ESID will
focus on two main points for Europe:
*
Implementation of neonatal screening for severe combined immunodeficiency
(SCID). After the success of the program in several states in the USA, ESID
will push for SCID screening to be established soon in many European countries.
* Provision of adequate treatment
of the various PIDs across Europe. Unfortunately, in many countries the supply
of intravenous immunoglobulin (IVIG) is inadequate and haematopoietic stem cell
transplantation (HSCT) centres have yet to be developed in some countries,
mainly in eastern Europe.
Although much has been achieved,
there is still a long way to go in providing the early and precise diagnosis of
PID, together with the appropriate treatment, to the many thousands of patients
all over Europe and the world.
Latin America
Organised efforts towards
improving the diagnosis and management of patients with PIDs in Latin America
started in 1993 when a small group of immunologists from Argentina, Brazil,
Chile and Colombia teamed up with Ricardo Sorensen, M.D., in the USA to create
a joint patient reporting form under the auspices of an informal group called
the Latin American Group for Primary Immunodeficiencies (LAGID). The goals of
this organization were to include other Latin American countries and to create
registries of patients with PIDs in each participating country. The group grew
from the initial four to a total of 14 countries with a wide population range.
Many of the objectives set forth
by LAGID have been accomplished, including: the development of patient and
parent support groups in most participating countries; the creation of a
website for members; the organization of 12 yearly scientific meetings held
from 1995 to 2007; educational programmes and the education of paediatricians
and general practitioners; and extensive collaborative efforts between member
countries and between Latin American immunologists and their colleagues in
Europe and the US. These efforts led to the creation of the first joint PID
registry published by eight countries in 1998 (6). A second report was published in 2007 (7)
A second official electronic
registry, following the model of the ESID registry, was established for all of
Latin America in Sao Paulo, Brazil, with the assistance of ESID. Other actions
have contributed to advancing the care of patients with PIDs in Latin America
and have brought a new dynamic to diagnosis, treatment and research in the
region (8,9). These
actions include the sponsored fellowship programme led by the Latin American
Society for Immunodeficiencies (LASID), founded in 2009, which has assisted
young immunologist in five countries to specialise in the diagnosis and care of
PIDs, and the establishment of a network of Jeffrey Modell Diagnostic and
Research Centers in Sao Paulo, Mexico City, Medellin, Chile and Buenos Aires.
Created by the Jeffrey Modell Foundation, these centres offer enhanced
diagnostic and treatment capabilities for PID across the world, including now
in Latin America. Health authorities in several countries, including Mexico,
Colombia, Argentina, Brazil and Chile, have now recognised PIDs as a special
group of diseases and facilitated access to treatment.
The present day challenges of
PID in Latin America are two-fold: to continue to expand awareness and
diagnosis and treatment possibilities to more areas in Latin America where
there has been little or no progress, and to satisfy the desire of young Latin
American immunologists to bring state-of-the-art advances in diagnosis and
treatment to their patients. The encouraging experience gained from years of
successful collaborative efforts allows LASID to look with great optimism to
its future.
Africa and Middle East
PID diagnosis and care in Africa
and the Middle East has developed tremendously over the past 2 years, but major
efforts are still needed, especially in Sub-Saharan Africa.
Indeed, we have witnessed the
creation of PID networks and the release of multicentre studies on these
conditions. In particular, two workshops bringing together experts from the
North Africa and Middle East were held in Athens in 2012 and in Dubai in 2013.
These led to the sharing of solutions between experts and to the building of
cooperative bridges in training and research. In 2011, Ridha Barbouche and
colleagues published a profile of PIDs in North Africa (Morocco, Tunisia and
Egypt), (10) while Saleh Al Muhsen and colleagues published on the
epidemiology of PID in the Middle East (11).
Both regions are characterised
by high rates of in-breeding (20–60%) and they have a comparable distribution
of PID causes, with a high incidence of SCID and founder mutations. Teams in
the Middle East, including Saudi Arabia, have published excellent results on
HSCT and have contributed to internationals research on PID specific cases
(12). PID treatment has been slower to develop in North Africa,
with difficulties existing in IVIG access and HSCT being introduced only
timidly.
These advances allow high hopes
for patients with PIDs in the aforementioned regions. However, with the
exception of South Africa — where the situation is comparable to that in North
Africa — progress is lagging in the rest of the African countries. Indeed,
there seems to be little or no activity in the PID field in over 40 of the 54
countries of this continent. To address this issue, the African Society for
Immunodeficiencies (ASID), created in Casablanca in 2008, opted for regional
actions to educate paediatricians and other healthcare professionals and to
promote cross-country initiatives to allow the exchange of expert experience
and education. ASID’s achievements are already palpable: Africa has a
spokesperson for PID scientific and social societies, and schools to provide
education about PIDs have involved a dozen countries in each region of Africa.
However, challenges remain in
Africa, whose population has this year exceeded 1 billion citizens, and urgent
international actions are necessary in this continent. These should aim not
only to increase awareness of PIDs among physicians, nurses and other
healthcare professionals, but in particular to bring the attention of the
authorities and the general public to this large group of rare diseases and
their significant effect on infant mortality. Indeed, PIDs are more common than
is generally thought. It is estimated that up to 900,000 people in Africa may
have a PID, whereas only around 1000 cases are currently registered (13).
The two regions of North Africa
and the Middle East have rightly decided to work together to improve PID
diagnosis and care. Corresponding joint efforts are also needed in the rest of
Africa to enable the work of patient groups, doctors and nurses to bring a
positive change for PID patients.
Australia
There is an active
immunodeficiency community in Australia, with many of the major interactions
revolving around the PID Committee of the Australasian Society of Clinical
Immunology and Allergy (ASCIA) and the now well-established triennial Asia
Pacific Primary Immune Deficiency (APPID) Summer School. While geographical
constraints make large PID centres difficult to envisage, there are a number of
major centres seeing patients with complex immunodeficiency disorders and the
first Australian Jeffrey Modell Foundation Center will soon open at Sydney
Children's Hospital, Randwick. The outcomes amongst the five centres currently
performing HSCT for PIDs in Australia compare favourably to those from other
parts of the world (14).
From a research perspective
there has been an effort to form collaborative research partnerships across the
country, initially through the Australian PID registry (15) and more
recently through the antibody deficiency orientated Australia and New Zealand
Antibody Deficiency Allele (ANZADA) study, which has now being joined by the
more paediatric-orientated CIRCA group.
As in other (but not all)
countries with similar economies, IVIG use is increasing by more than 10% per
annum. In Australia most IVIG use is funded by the federal government (16) and
distributed through the Red Cross Blood Service. A study in New South Wales is
interrogating the Red Cross database to improve our understanding of the
factors driving these changes. Subcutaneous immunoglobulin (SCIG) is becoming
increasing popular among PID patients. SCIG appears to require lower overall
immunoglobulin doses and some centres report that more patients are now using
SCIG rather than IVIG. Although three products have been approved by regulatory
authorities for SCIG use, and SCIG has been endorsed in the Australian criteria
for the clinical use of immunglobulin (http://www.nba.gov.au/ivig/index.html),
national funding of SCIG use is still awaited.
Conclusion
The last 10 years has seen an
unprecedented improvement in PID care in many areas of the world, including
some areas where provision was seriously lacking. These improvements have
resulted from collaborative efforts involving immunologists, non-specialist
physicians, nurses’ associations, health providers, policymakers, and patient
organisations. Such collaborations offer a model for further efforts to promote
early diagnosis and therapy in order to extend and improve the lives of people
with PIDs, especially in areas of greatest need.
References
1.
Eades-Perner AM, Gathmann B, Knerr V, Guzman D, Veit D, Kindle G, Grimbacher B;
ESID Registry Working Party. The European internet-based patient and research
database for primary immunodeficiencies: results 2004-06. Clin Exp Immunol
2007;147:306–12
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Gathmann B, Grimbacher B, Beauté J, Dudoit Y, Mahlaoui N, Fischer A, Knerr V,
Kindle G; ESID Registry Working Party. The European internet-based patient and
research database for primary immunodeficiencies: results 2006-2008. Clin Exp
Immunol 2009;157 Suppl 1:3–11
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Gathmann B, Binder N, Ehl S, Kindle G; ESID Registry Working Party. The
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de Vries E; European Society for Immunodeficiencies (ESID) members. Patient-centred
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5. Maródi L, J Project Study
Group. The creation and progress of the J Project in Eastern and Central
Europe. Ann NY Acad Sci 2011;1238:65-73
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Zelazko M, Carneiro-Sampaio M, Cornejo de Luigi M, Garcia de Olarte D, Porras
Madrigal O, Berrón Perez R, et al. Primary immunodeficiency diseases in the
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13. Bousfiha AA, Jeddane L,
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Mitchell R, Nivison-Smith I, Anazodo A, Tiedemann K, Shaw P, Teague L, et al.
Outcomes of hematopoietic stem cell transplantation in primary
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16. National Blood Authority
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March 2013]
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