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Severe combined immunodeficiency

This is part of Rare diseases.

Diagnosis: Severe combined immunodeficiency

Synonyms: SCID

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Publication date: 2013-03-12
Version: 3.0

The disease

Severe combined immunodeficiency (SCID) is the collective name for the most serious of the congenital immunodeficiency disorders, characterised by a severely weakened or absent immune system. They are group of disorders with similar symptoms, treated in the same ways, but with different underlying genetic causes.

Although the condition is rare, with many different causes, it plays an important role in our understanding of how the immune system works. Extensive research is therefore underway to map the different genetic mutations and how they lead to a decline in vital immune functions.

Occurrence

The estimated incidence of children born with severe combined immunodeficiency in Sweden is two or three per year. Today (2013) there are approximately twenty persons in the country who were born with different forms of SCID, but who have undergone haematopoietic stem cell transplantation (HSCT) and are now healthy.

Cause

Today there are almost 20 known causes of severe combined immunodeficiency. In all of these disorders the deficiency knocks the immune system partially or completely out of action.

The immune system consists of an elaborate set of mechanisms which interact to protect us against bacteria, viruses and other pathogens. There is a distinction between innate immunity and adaptive immunity. There are also a number of natural mechanisms in, for example, the skin, mucous membranes and the acids of the stomach, which protect us against infection.

The innate immune system consists of many different proteins, certain types of white blood cells such as phagocytes (cells that ingest other cells), and natural killer (NK) cells. On their surfaces phagocytes have different receptors which recognise certain pathogens, enabling them to destroy many of these invading micro-organisms. Other cells contain similar receptors which can recognise dangerous substances, irrespective of whether these substances have been produced by the body or originate from an external source.

The adaptive immune system collaborates with the innate immune system. It recognises specific pathogens, and can tailor a response that will kill those particular substances. The adaptive immune system memorises its responses and successively becomes more effective.

Two types of white blood cells, B cells and T cells, play a key role in the adaptive immune system. These cells are also called T lymphocytes and B lymphocytes and are formed by the blood stem cells in bone marrow. The role of B cells is to create antibodies which attach to the pathogen and then activate the phagocytes which destroy it. T cells have several different functions. They can activate B cells so that they produce antibodies, attack cells infected by viruses and release an element (cytokines) which attracts phagocytes to cells infected by viruses. T cells also have the vital role of regulating our immune systems, deciding when we need to defend ourselves, and against what. They also determine when we suspend an immune reaction. Certain T cells also assist both B cells and other T cells.

Blood cells which are going to develop into T cells start their development in the bone marrow, and then move to the thymus, a gland in the upper part of the chest cavity, where they mature and “learn” their role. The loss of thymus function may therefore result in a severe combined immunodeficiency, as seen for example in the 22q11-deletion syndrome and CHARGE syndrome. Separate information on these disorders is available in the Rare Disease Database of the Swedish Board of Health and Welfare.

In severe combined immunodeficiency the individual’s immune defence system is partially or totally out of function. This may be because T cells are absent, that their functionality has been compromised or that the “training” of the T cells is not working. The different varieties of the disease are the result of different congenital factors

Gene    Protein Chromosome  Symptoms not related to immunodeficiency
IL2RG Interleukin-2 receptor gamma chain  Xq13
JAK3 Janus activated kinase 3 (JAK3)  19p13.1
IL7A Interleukin-7 receptor a chain  5p13.2
RAG1 Recombination activating protein 1 (RAG1)  11p13
RAG2 Recombination activating protein 2 (RAG2)  11p13
ADA Adenosine deaminase  20q13.11
AK2 Adenylate kinase 2  1p35.1 Deafness

Table: The hitherto known genes associated with severe combined immunodeficiency in Sweden.

Six groups of severe T cell defects resulting in severe combined immunodeficiency have been diagnosed in Sweden. The different genes (see table) are:

  • Defects in the common gamma chain of certain interleukin receptors
  • JAK3 deficiency
  • Interleukin 7 receptor alpha chain deficiency
  • RAG1 and/or RAG2 deficiency, including Omenn syndrome
  • ADA (adenosine deaminase) deficiency
  • Reticular dysgenesis

There are several other types of severe combined immunodeficiency. These have not yet been diagnosed in Sweden but have been found in individuals from other parts of the world. One example is ADA deficiency (adenosine deaminase deficiency) which, in Sweden, is found only in individuals whose origins are in the Middle East.

Inherited X-linked form of SCID

Over half of all individuals with SCID have this variant, caused by a mutation in the IL2RG gene, which codes for the interleukin-2 receptor gamma chain. This is the most prevalent form of SCID. It is caused by a defect in an immune system cell receptor for signal substances known as interleukins (IL).

Interleukins are proteins which act as important messengers between the cells of the immune system. They are involved in cell maturation, development and activation. In this specific form of SCID one of three protein chains, common for interleukin receptors 2, 4, 7, 15 and 21, is defective. The defective interleukin 7 receptor is thought to be the main reason for the lack of T cells, as interleukin 7 is an essential growth factor in the early stages of T cell maturation. The form of severe combined immunodeficiency linked to the X chromosome is characterised by the absence of T cells or a very low T cell count. The condition is also associated with normal or elevated B cell counts, and absent NK cells. There are no NK cells, as interleukin 15 is necessary for their maturation.

Inherited autosomal recessive forms of SCID

JAK3 deficiency is one of several forms of SCID that has an autosomal recessive pattern of inheritance. This means that the condition is inherited through a mutated gene located on an autosome, which is a non sex-determining chromosome (see under “Inheritance”).

The interleukins act as messengers between the cells of the immune system, while JAK3 is a mediator within the T cells. This protein acts as an intermediary between the receptor on the cell surface (the message passing via several other mediators), and the cell nucleus and genetic material. This signal activates one or several genes. One of the roles of JAK3 is to signal that the interleukin 7 receptor has been activated. A defective JAK3 gene leads to the same type of damage to the immune system as in those cases of severe combined immunodeficiency linked to the X chromosome. In these cases, T and NK cells do not develop, and children with this disease have no T cells, while their levels of B cells (lymphocytes) are normal or elevated.

If SCID results from absence of the alpha chain in the receptor for interleukin 7, the cause is a mutation in gene IL7RA, which codes for the alpha chain in the receptor. This gene is located on chromosome 5 (5p13.2). The result is that no T cells are formed but, unlike the two forms of severe combined immunodeficiency described previously, only T cells are absent, while B and NK cells develop normally.

SCID arising from an absence of one of the proteins RAG1 or RAG2 is known as RAG1 and/or RAG2, or Omenn syndrome. RAG stands for recombinase activation gene. RAG1 and RAG2 have important and complex functions in the development of lymphocytes and the formation of receptors which can recognise specific substances and mobilise a specific immune defence against them.

In the first stage in the development of the proteins that form a part of these receptors (T and B lymphocyte receptors), two or three genes, depending on the different chain of proteins in the receptor, come together and create a new gene. The redundant middle parts of the chromosome thread are simply cut off. Two proteins act as the “scissors” in this process, and a group of other proteins function as “glue”, binding the ends together. RAG1 and RAG2 make up these “scissors.” If either of these proteins is missing, it is impossible for new genes to be created, and no T or B lymphocyte receptors can be formed. Without receptors neither T cells nor B cells develop. Severe combined immunodeficiency associated with RAG1 or RAG2 deficiency is characterised by an almost complete absence of T and B lymphocytes.

Although ADA deficiency (adenosine deaminase deficiency) is very rare in Sweden, it represents up to 20 per cent of cases worldwide. ADA deficiency affects a protein essential for chromosome degradation. In our bodies, cell generation and cell death occur continuously. The immune system alone produces millions of cells per second. An equal number of cells die and the resulting products must be taken care of and recycled. ADA is essential for breaking down nucleic acids, one of the building blocks of our genes. When ADA deficiency impairs degradation, metabolic by-products accumulate, with a toxic effect on T and B cells. The cells die, resulting in severe combined immunodeficiency.

During the foetal stage the mother metabolises the toxic by-products, and it is not until after birth that immunodeficiency develops. In some cases of mild ADA deficiency, severe immunodeficiency does not develop until adulthood.

Reticular dysgenesis is one of the least common forms of SCID. The underlying cause of the disease was first identified in 2008. Reticular dysgenesis is characterised by impaired lymphocyte and phagocyte production, meaning that neither the adaptive nor the innate immune system works properly. An early sign of phagocyte deficiency is that the umbilical cord stump fails to fall off when expected, often not until the infant is between six and eight weeks old. Children with reticular dysgenesis are deaf.

Reticular dysgenesis is a mitochondrial disease (there is specific information about mitochondrial diseases in the Rare Disease Database of the Swedish National Board of Health and Welfare). The reason is a mutation in gene AK2, which governs the development of (codes for) the protein adenylate kinase 2 which, in turn, plays an important role in energy production in cells. Almost all the cells in the body have one more protein, adenylate kinase 1, which has the same function as adenylate kinase 2. However, white blood cells (T cells, B cells, NK cells and phagocytes) and the cells of the inner ear contain only adenylate kinase 2. This explains why the immune system is affected. The reason that hearing is affected is thought to be that adenylate kinase 2 protects the inner ear against damage from energy-rich substances. The absence of the protein results in these substances accumulating, thus damaging the blood supply to the inner ear.

Hypomorph mutations

The typical symptoms of severe combined immunodeficiency arise in children with mutations that eliminate gene activity and lead to complete absence of the encoded protein. These mutations are known as amorphic.

Hypomorphic mutations are also common. These reduce but do not eliminate gene activity, and the encoded protein will retain some degree of function.

Omenn syndrome is an example of a condition that results from a hypermorphic mutation in one of the genes in which amorphic mutations lead to severe combined immunodeficiency. In Sweden, hypermorphic mutations most commonly occur in RAG1 or RAG2. Occasionally Omenn syndrome may also occur as a consequence of an IL7RA mutation. If RAG1 and RAG2 proteins are present in small amounts, or are not fully functional, some defective T cells may be formed. As they do not function properly, the normal process controlling the development and function of the T cells in the thymus is also impaired. The consequence is a particular form of severe combined immunodeficiency with specific characteristics including allergies and eczema-like rashes with dry and flaking skin. These are in addition to the many infections which characterise all forms of severe combined immunodeficiency.

In other cases considerably more function is retained, meaning that symptoms may be very mild. The onset may not occur until adolescence or adulthood, as when the condition results from hypomorphic mutations in the ADA gene.

Heredity

Severe combined immunodeficiency is associated with different patterns of inheritance depending on the underlying cause (see under “Cause”).

An autosomal recessive inheritance pattern means that both parents are healthy carriers of a mutated gene. In each pregnancy there is a 25 per cent risk that the child will inherit double copies of the mutated gene (one from each parent), in which case the child will have the disease. In 50 per cent of cases the child inherits only one mutated gene (from one parent only) and like both parents, will be a healthy carrier of the mutated gene. In 25 per cent of cases the child will not have the disease and will not be a carrier of the mutated gene.

Figure: Autosomal recessive inheritance

A person with an inherited autosomal recessive disease has two mutated genes. If this person has a child with a person who is not a carrier of the mutated gene, all the children will inherit the mutated gene but they will not have the disorder. If a person with an inherited autosomal recessive disease has children with a healthy carrier of the mutated gene (who has one mutated gene) there is a 50 per cent risk of the child having the disorder, and a 50 per cent risk of the child being a healthy carrier of the mutated gene.

An X-linked recessive inheritance pattern is caused by a mutated gene located on the X chromosome, which is one of the chromosomes determining sex. Men have one X chromosome and one Y chromosome, while women have two X chromosomes. Inherited X-linked recessive disorders usually occur only in men, being passed down via a healthy female carrier who has one normal and one mutated gene. Sons of female carriers of a mutated gene run a 50 per cent risk of inheriting the disease and daughters run the same risk of being healthy carriers of a mutated gene. A man with an inherited X-linked recessive disease can not pass it on to his sons, but all his daughters will be carriers of the mutated gene.

The X-linked recessive form of severe combined immunodeficiency can also be caused by a new mutation. This means that the genetic mutation occurs in an individual for the first time and is not inherited from either parent. Consequently, parents with a child with a new mutation generally do not have an increased risk of having another child with the disorder. However, the new genetic mutation will be hereditary and an adult with this mutation risks passing on the mutated gene to his/her children. Severe combined immunodeficiency caused by an IL2RG mutation is a special situation as the new mutation has often occurred in the mother of an affected boy. As women have two X chromosomes the mother will not be affected, but all her sons have a 50 per cent risk of having the disorder.

Figure: X-linked recessive inheritance  via a healthy female carrier

Symptoms

Children with severe combined immunodeficiency are susceptible to frequent, severe infections from an early age. They often have several infections at once. Apart from infections that affect individuals with normal immune systems, children with severe combined immunodeficiency may develop life-threatening infections from bacteria and viruses which pose no threat to healthy individuals.

What we regard as an infection is in most cases the result of our immune system’s reaction to a pathogen. Pus in an infected wound, feeling unwell, having a raised temperature, cough or runny nose are signs that the inflammatory process has been activated in the body. As the immune system in children with severe combined immunodeficiency either does not work, or works very poorly, symptoms resulting from infections are often deceptively mild. For example, it may take months before a serious pulmonary inflammation is discovered if the early symptoms are limited to a mild cough and respiratory catarrh.

Early symptoms of severed combined immunodeficiency include respiratory infections and chronic diarrhoea. Persistent fungal infections affecting the skin and mucous membranes are common, and may not respond well to treatment. Children with this disorder often fail to grow and gain weight.

Skin rashes are common. They are mainly of two types, both of which may be mistaken for severe eczema. One form may result from a reaction caused by maternal T cells having been transferred to the baby during delivery. It is normal that some blood passes from mother to child during delivery but if the infant’s immune system is healthy the infant’s own T cells will destroy other T cells. However, as an infant with this disorder has no immune response to combat invading cells, the mother’s T cells can survive and will attempt to reject the infant’s tissues.

Skin rashes may also be caused by activated T cells. This condition is referred to as Omenn syndrome and this variant of the disorder is usually associated with impaired T and B cell receptor formation. Sometimes the child will develop a few T cells. However, as the normal regulatory system is non-functioning their activation may be uncontrolled and cause a severe inflammatory reaction in the skin as well as in most of the internal organs.

Children with this disorder experience lengthy and persistent infections, the symptoms of which become increasingly serious. Viral infections pose a particular threat, as in most cases they do not respond to antibiotic treatment. These infections tend to spread and become chronic, destroying cells and tissues. Without haematopoietic stem cell transplantation infants with severe combined immunodeficiency die before the age of one as a result of infections, or from a rejection reaction, caused by lymphocytes transferred to the child from the mother.

In cases of reticular dysgenesis the child is born deaf.

Diagnosis

Although the symptoms of severe combined immunodeficiency are initially mild, these children are very ill. Life expectancy is dependent on early diagnosis, preferably in the first three months of life. The earlier the diagnosis is made, the smaller the risk that the infant will suffer severe infections with associated tissue damage. This is a particularly important consideration when it comes to stem cell transplantation.

Diagnosis of severe combined immunodeficiency is difficult, as symptoms are diffuse and frequently present in otherwise healthy children. Paediatricians should therefore pay special attention to combinations of persistent infections, involving, for example, chest X-rays revealing unexpectedly severe pulmonary changes, diarrhoea, failure to gain weight , and fungal infections affecting the mouth (visible as a white coating) and rectal area. Severe combined immunodeficiency should also be considered in unexplained cases of eczema-like skin rashes. A simple screening test can measure the total blood lymphocyte count. Healthy infants normally have a much higher lymphocyte count than older children or adults. In contrast, at least 80 per cent of all infants with the disorder have a low lymphocyte count (less than 2 billion lymphocytes per litre of blood).

When severe combined immunodeficiency is strongly suspected, or as soon as the diagnosis is confirmed, the child should immediately be referred to a specialist clinic. This is a life-threatening condition if treatment is not initiated promptly.

The underlying mutations are known in all cases of severe combined immunodeficiency diagnosed in Sweden. In most cases it is therefore possible to identify whether other relations, such as siblings, are carriers of the mutated gene. At the time of diagnosis the family should be offered genetic counselling. Carrier and prenatal diagnostics, as well as pre-implantation genetic diagnostics (PGD) in association with IVF (in vitro fertilization), are available in families where the mutation is known.

Within approximately a year (in 2014), severe combined immunodeficiency will be a part of the Swedish national screening programme, in which a number of disorders are diagnosed via the PKU test administered to all newborns in Sweden.

Treatment/interventions

Haematopoietic stem cell transplantation (bone marrow transplant) is the only cure for severe combined immunodeficiency. Only in cases of ADA (adenosine deaminase) deficiency is it possible to treat the condition by life-long administration of the missing substance. Treatment involves once or twice weekly subcutaneous injections of ADA, in combination with a chemical substance which extends its function, for the rest of the individual’s life.

Haematopoietic stem cell transplantation

All blood cells are produced from blood stem cells (haematopoietic stem cells) in the bone marrow. Blood-forming stem cells can develop into red blood cells (erythrocytes), different types of white blood cells including lymphocytes and blood platelets (thrombocytes). In a stem cell transplantation a sick person’s bone marrow is replaced with that of a healthy person. To optimise the chances of successful transplantation, the recipient of the marrow should be as free from infection as possible and in good physical condition. For this reason, it is important to carry out the transplantation at an early stage. The intervention itself is fairly simple, but the preparations, aftercare and major risks make it a highly demanding procedure.

In order to carry out a stem cell transplantation, a donor must be found whose tissue type (HLA type) matches that of the recipient. Ideally the tissue type should be identical. Tissue type is inherited from both parents, and each child has a 25 per cent chance of having the same tissue type as a sick sibling. The optimal solution is to transplant stem cells from an HLA-identical, healthy sibling. If this is not possible a suitable donor may be located in national and international bone marrow donor programmes or in stored, frozen blood from umbilical cords. The “Tobias Registry” in Sweden contains approximately 40,000 registered voluntary donors, and the names of more than 20 million other donors can be found in registers outside Sweden.

Preparatory measures are needed to help the new stem cells engraft and minimise the risk of diseased cells attacking the new donor cells. The recipient of the transplanted cells is treated with chemotherapy. This treatment can be extremely exacting as chemotherapy also impairs the barrier function of the mucous membranes. There is a major risk of developing serious infection and for this reason the child needs to be kept in isolation for a period of weeks or sometimes months prior to and after the transplantation.

In a blood stem cell transplantation, bone marrow is drawn from the donor’s hip bone and is then administered to the recipient via drip, directly into the bloodstream, much as in a blood transfusion. Blood stem cells can also be collected from the donor’s blood. The blood is then filtered in a special kind of centrifuge which separates the stem cells from the rest of the blood, which can then be returned to the donor. A third option is to use umbilical cord blood from newborns, which is particularly rich in blood stem cells. The blood of newborns has very high levels of blood stem cells and the small amount of blood remaining in the umbilical cord of a healthy newborn can be frozen and saved for later transplantations.

Regardless of their source, the transplanted blood stem cells find their way into the bone cavities of the recipient, and grow in the bone marrow to supply the child with a new immune system.

The prognosis for curing severe combined immunodeficiency is dependent on the child’s age at the time of transplantation and the availability of a compatible donor. If cells from a sibling with identical HLA are transplanted when the affected infant is around one month old, and no pre-transplant chemotherapy is needed, the chances of recovery are as high as 100 per cent. If the child does not have a sibling with identical HLA, and an unrelated donor with identical HLA cannot be found within approximately a month, stem cells from blood from an umbilical cord may be used. Medical literature indicates a very high success rate when the procedure takes place early, with between 65 and 90 per cent of children making a full recovery.

Unfortunately, only a minority of affected infants have an ideal donor. Transplantation in the early months of life is generally only possible if a sibling or other family member has previously been affected, thus enabling early diagnosis during the foetal stage or the first few weeks of life. If the diagnosis is delayed and the transplant cannot be performed during the first six months of life, the child has usually had several viral infections, decreasing the chances of successful transplantation. In some rare cases, haematopoietic stem cell transplantation proves impossible at this point.

Gene therapy

Approximately 40 children with X-linked severe combined immunodeficiency or ADA (adenosine deaminase) deficiency have undergone gene therapy, and in the majority of cases results have been successful. In simplified terms, gene therapy involves “repairing” the mutation by inserting a normal gene into the genome of the affected child. To be able to cure inherited diseases in this way has long been the dream of affected families and scientists, and intensive research in the last 10 to 20 years has enabled it. However, the difficulties have also proved to be considerably greater than foreseen. Severe immunodeficiency disorders are hitherto the only diseases in which gene therapy has been successful.

Gene therapy is currently reserved for the few children with severe combined immunodeficiency linked to the X chromosome, and for children with ADA deficiency where it has not been possible to find a donor with the same tissue type as the child.

In practical terms gene therapy involves using a virus with the ability to insert its genes into human genetic material. The safety procedures are rigorous. First, all the disease-causing genes in the virus are removed and a healthy copy of the gene which is to be repaired is inserted into the virus genome. The new virus contains a healthy copy of a human gene and cannot cause any harm. It must also retain its ability to insert its genes into the host’s genome, so that it can “infect” the bone marrow of the affected child. A small amount of the child’s bone marrow has previously been removed from the hipbone by suction, and the virus is now introduced into this sample of bone marrow in the laboratory. The aim is for the re-engineered virus to incorporate the new healthy gene into the genetic material in the blood stem cells, resulting in a permanent change.

The healthy gene incorporates at random into the genetic material and may not reach its intended destination, i.e. the position where the gene is located in healthy individuals. The random placement of the new gene means that it may end up in an unsuitable location near, or in the middle of, another gene. The resulting complications may be serious. Unfortunately, five children with severe combined immunodeficiency linked to the X gene, who underwent seemingly successful gene therapy, developed leukaemia a year or so after the treatment. The new gene was in the wrong position and activated another gene that induced abnormal white blood cell development. However, no children with ADA deficiency have developed leukaemia as a result of gene therapy.

Supplementary treatment

These children have a combined deficiency, meaning that they also do not produce antibodies (gamma globulin). Gamma globulin is therefore administered intravenously before and after the transplantation, before the new stem cells have begun to function normally, and provides excellent protection against bacterial infections.

Gamma globulin is a concentrate of antibodies drawn from the plasma of several blood donors. The blood from each donor is thoroughly screened for infections such as hepatitis and HIV. Blood plasma is treated to eliminate risks from viruses or bacteria. The result is a liquid containing purified IgG antibodies as well as very small quantities of IgA and IgM antibodies.

Infections should be treated aggressively and prophylactic antibiotics are usually prescribed. Examples include trimethoprim, an antibiotic effective for treating infections caused by the single-celled fungus Pneumocystis jerovici, and antifungal medications used to treat other fungal infections, for example, thrush (Candida).

Corticosteroids and immune suppressants are used to treat skin symptoms, regardless of whether they are caused by a rejection reaction or by Omenn syndrome.

Blood transfusions and vaccines

It is important to understand that in severe combined immunodeficiency the immune system is very seriously damaged. Even common, established therapies can be life-threatening. Live vaccines or non-irradiated blood products must never be administered to children with suspected or confirmed severe combined immunodeficiency. The use of live vaccines in children with this disorder has life-threatening consequences. These children have no defence against pathogens, and a vaccine such as BCG, which is used for tuberculosis immunization, causes the spread of a tuberculosis-like condition, which is often fatal.

Vaccines provide no benefit to individuals with this condition as they are intended for healthy immune systems that can be stimulated by the deactivated pathogens in the vaccine.

Blood contains T cells (lymphocytes). In a normal blood transfusion, this is not a problem as the few T cells transferred are eliminated by the recipient’s healthy T cells. However, a child with severe combined immunodeficiency cannot reject the donor’s T cells, and so they can trigger a fatal rejection reaction directed against the child. Blood products intended for children with severe immunodeficiency disorders must therefore always be irradiated in order to kill the donor’s T-cells.

Individuals who have undergone haematopoietic stem cell transplantation are treated temporarily with immunosuppressive drugs, and will continue to have regular medical check-ups throughout life. These are necessary to identify any signs of rejection (graft-versus-host reaction, GvH), or other complications, and to see that the immune system recovers as expected. There may also be other, disease-specific, reasons for scheduling regular check-ups. In severe combined immunodeficiency it is particularly important that the immune system recovers to normal so that immunoglobulin treatment can be discontinued and vaccinations begin. It may also be the case that infections have caused damage, for example in the lungs, which demands follow-up.

Practical advice

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National and regional resources in Sweden

Diagnostics, assessment and treatment are provided at the Queen Silvia Children’s Hospital, Department of Paediatric Immunology, SE-416 85 Gothenburg, Sweden. Tel: +46 31 343 40 00.

Resource personnel

Professor Anders Fasth, Unit for Paediatric Immunology, The Queen Silvia Children’s Hospital, SE-416 85 Gothenburg, Sweden. Tel: +46 31 343 40 00, fax: +46 31 84 30 10, email: anders.fasth@gu.se.

Courses, exchanges of experience, recreation

PIO, The Primary Immunodeficiency Organization in Sweden, offers training, support, information and the opportunity to meet others in the same situation. PIO publishes information and organizes regular lectures and information meetings for people with primary immunodeficiency disorders, their relatives and other interested parties. Weekend courses are held annually for children and young people with primary immunodeficiency disorders and their families. Regular joint meetings over several days are held with members of the Nordic immunodeficiency organizations. For further information contact PIO. Find address under “Organizations for the disabled/patient associations” below.

IPOPI, the International Patient Organisation for Patients with Primary Immunodeficiencies, of which PIO is an affiliate, arranges a conference in conjunction with a biennial international medical conference for doctors and nurses interested in immunodeficiency. IPOPI conferences are conducted in English. For further information, contact PIO, under “Organizations for the disabled/patient associations.”

Organizations for the disabled/patient associations etc.

PIO, The Primary Immunodeficiency Organisation in Sweden, Mellringevägen 120 B, SE-703 53 Örebro, Sweden. Tel: +46 19 673 21 24, email: info@pio.nu, www.pio.nu.

Courses, exchanges of experience for personnel

SLIPI, the Swedish Physicians’ Association for Primary Immunodeficiencies organises meetings and conferences, www.slipi.nu.

SISSI, the Swedish Nurses’ Association for Primary Immunodeficiencies. The association publishes a worksheet and has regular conferences for members. In alternate years this is organized in collaboration with ESID, IPOPI and INGID, www.sissi.nu.

ESID, the European Society for Immunodeficiencies.
The Society has regular international conferences and summer schools for doctors and researchers, www.esid.org.

INGID, the International Nursing Group for Immunodeficiencies. The Group arranges international meetings in collaboration with ESID and the international patient organization IPOPI, www.ingid.org.

Research and Development

Anders Fasth, Department of Paediatric Immunology, The Queen Silvia Children’s Hospital, SE-416 85 Gothenburg, Sweden.

Alain Fischer, Hôpital Necker - Enfants Malades, Inserm U429, 149 Rue De Sevres, 750 15 Paris Cedex, France.

Luigi D Notarangelo, Division of Immunology and The Manton Center for Orphan Disease Research, Children’s Hospital, Harvard Medical School, Boston MA 02115, USA.

Klaus Schwartz, University of Ulm, Helmholhstr 10, 89 081 Ulm, Germany.

Information material

An information leaflet on sever combined immunodeficiency summarising the information in this database text is available free of charge from the Publication Department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2012-10-9.) Address: SE-106 30 Stockholm, Sweden. Fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se, or tel: +46 75 247 38 80. Postage will be charged for bulk orders.

Patient and Family Handbook for the Primary Immune Deficiency Diseases. (In English.) IDF- Immune Deficiency Foundation, fourth edition, USA 2007. This book may be downloaded as a PDF file from the organisation’s website, http://primaryimmune.org/about-primary-immunodeficiency-diseases/publications/patient-family-handbook.

The material below can be ordered from PIO (Primary Immunodeficiency Organization). See contact information under “Organizations for the disabled/patient associations etc.” Unless otherwise mentioned, in Swedish only.

  • Primär immunbrist hos barn och vuxna. Ninth edition, 2010.
  • Så mår immunförsvaret bättre. Living with primary immunodeficiency. Some practical advice, 1999.
  • The story of primary immunodeficiency (In English), 1999.
  • En skola för alla. Practical advice on creating a better school environment for those with primary immunodeficiency. One brochure for the institution and one for the student. Third edition, 2012.
  • Studera med primär immunbrist. Practical advice for university or college students with primary immunodeficiency. One brochure for the institution and one for the student. First edition, 2008.
  • Lathund för ansökan av vårdbidrag. Updated, 2012.

Literature

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Al-Herz W, Bousfiha A, Casanova JL, Chapel H, Conley ME, Cunningham-Rundles C et al. Primary Immunodeficiency Diseases: an update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. Front Immunol 2011; 2: 54.

Bertrand Y, Landais P, Friedrich W, Gerritsen B, Morgan G, Fasth A et al. Influence of severe combined immunodeficiency phenotype on the outcome of HLA non-identical, T-cell-depleted bone marrow transplantation: a retrospective European survey from the European group for bone marrow transplantation and the European society for immunodeficiency. J Pediatr 1999; 134: 740-748.

Cavazzano-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon E, Nusbaum P et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 2000; 288: 669-672.

Eapen M, Ahn KW, Orchard PJ, Cowan MJ, Davies SM, Fasth A et al. Long-term survival and late deaths after hematopoietic cell transplantation for primary immunodeficiency diseases and inborn errors of metabolism. Biol Blood Marrow Transplant 2012 Mar 16. [Epub ahead of print]

Gaspar HB, Bjorkegren E, Parsley K, Gilmour KC, King D, Sinclair J et al. Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning. Mol Ther 2006; 14: 505-513.

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Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P et al on behalf of members of European Group for Blood and Marrow Transplantation and European Society for Immunodeficiency. Long Term Survival and Transplantation of Haematopoietic Stem Cells for Primary Immunodeficiencies; Report of the European Experience 1968-2005. J Allerg Clin Immunol 2010; 126: 602-610.

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Databasreferenser

OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim 
Search: severe combined immunodeficiency

GeneReviews (University of Washington)
www.genetests.org (select “GeneReviews”, then “Titles”)
search: X-linked severe combined immunodeficiency,
adenosine deaminase-deficient severe combined immunodeficiency disease

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft of this information material is Professor Anders Fasth, The Queen Silvia Children’s Hospital, Gothenburg, Sweden.

The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Publication date: 2013-03-12
Version: 3.0
Publication date of the Swedish version: 2012-11-29

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 422, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.

 

About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.