IDF Patient & Family Handbook for Primary Immunodeficiency ... - IDFA

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chapter 8 Hyper IgM Syndrome Patients with the Hyper IgM Syndrome have an inability to switch their antibody (immunoglobulin) production from IgM to IgG, IgA, and IgE. As a result, patients have decreased levels of IgG and IgA and normal or elevated levels of IgM. A number of different genetic defects can cause the Hyper IgM Syndrome. The most common form is inherited as an X-chromosome linked trait and affects only boys. Most of the other forms are inherited as autosomal recessive traits and affect both girls and boys.
Hyper IgM Syndrome 43 Definition of Hyper IgM Syndrome Patients with Hyper IgM (HIM) syndrome have an inability to switch production of antibodies of the IgM type to antibodies of the IgG, IgA, or IgE type. As a result, patients with this primary immunodeficiency disease have decreased levels of serum IgG and IgA and normal or elevated levels of IgM. B-lymphocytes can produce IgM antibodies on their own, but they require interactive help from T-lymphocytes in order to switch antibody production from IgM to IgG, IgA and IgE. The hyper IgM syndrome results from a variety of genetic defects that affect this interaction between T-lymphocytes and B-lymphocytes. The most common form of hyper IgM syndrome results from a defect or deficiency of a protein that is found on the surface of activated T-lymphocytes. The affected protein is called “CD40 ligand” because it binds to a protein on B-lymphocytes called CD40. CD40 ligand is made by a gene on the X-chromosome. Therefore, this primary immunodeficiency disease is inherited as an X-linked recessive trait and usually found only in boys. As a consequence of their deficiency in CD40 ligand, affected patients’ T-lymphocytes are unable to instruct B-lymphocytes to switch their production of immunoglobulins from IgM to IgG, IgA and IgE. In addition, CD40 ligand is important for other T-lymphocyte functions, and therefore, patients with X-linked hyper IgM syndrome (XHIM) also have a defect in some of the protective functions of their T-lymphocytes. Other forms of HIM syndrome are inherited as autosomal recessive traits (see chapter titled Inheritance) and have been observed in females and males. The molecular bases for some of the other forms of HIM have been discovered. These forms of HIM syndrome result from defects in the genes that are involved in the CD40 signaling pathway. Genetic defects in CD40 are very rare and have been described in few families. The resulting disease is almost identical to XHIM because although the CD40 ligand is present on T-lymphocytes, the CD40 found on B-lymphocytes and other cells of the immune system is either not present or does not function normally. Two other genes (AID and UNG) have been identified that are necessary for B-lymphocytes to switch their antibody production from IgM to IgG, IgA or IgE. Defects in both of these genes have been found in patients with HIM syndrome. Since the function of these genes is limited to antibody switching, the other T-lymphocyte functions of CD40 ligand are not affected, and these patients are less likely to have infections caused by organisms that are controlled by T-cells. Finally, a defect in another X-linked gene that is necessary for the activation of the signaling molecule NF-qB has been identified in a form of HIM that is associated with a skin condition called ectodermal dysplasia. Patients have immunodeficiency with sparse hair and conical teeth among other abnormalities. NF-qB is activated by CD40 and is necessary for the signaling pathway that results in antibody switching. NF-qB is also activated by other signaling pathways that are important in fighting infections. Therefore, these affected boys are susceptible to a variety of serious infections. Clinical Presentation of Hyper IgM Syndrome Most patients with Hyper IgM (HIM) syndrome develop clinical symptoms during their first or second year of life. The most common problem is an increased susceptibility to infection including recurrent upper and lower respiratory tract infections. The most frequent infective agents are bacteria. A variety of other microorganisms can also cause serious infections. For example, Pneumocystis jiroveci (carinii) pneumonia, an opportunistic infection, is relatively common during the first year of life and its presence may be the first clue that the child has the X-linked form of HIM syndrome (XHIM). Lung infections may also be caused by viruses such as Cytomegalovirus and fungi such as Cryptococcus. Gastrointestinal complaints, most commonly diarrhea and malabsorption, have also been reported in some patients. One of the major organisms causing gastrointestinal symptoms in XHIM is Cryptosporidium that may cause sclerosing cholangitis, a severe disease of the liver. Approximately half of the patients with XHIM syndrome develop neutropenia (low white blood cell count), either transiently or persistently. The cause of the neutropenia is unknown, although most patients respond to treatment with the
Page 1 and 2: Patient & Family Handbook For Prima
Page 3 and 4: Patient & Family Handbook For Prima
Page 5 and 6: Patient and Family Handbook i Prefa
Page 7 and 8: Patient and Family Handbook iii Abo
Page 9 and 10: The Immune System and Primary Immun
Page 11 and 12: The Immune System And Primary Immun
Page 19 and 20: Common Variable Immune Deficiency c
Page 21 and 22: Common Variable Immune Deficiency 1
Page 23 and 24: X-Linked Agammaglobulinemia chapter
Page 25 and 26: X-Linked Agammaglobulinemia 17 Clin
Page 27 and 28: Selective IgA Deficiency chapter 4
Page 29 and 30: Selective IgA Deficiency 21 Clinica
Page 31 and 32: Severe Combined Immunodeficiency ch
Page 33 and 34: Severe Combined Immunodeficiency 25
Page 39 and 40: Chronic Granulomatous Disease 31 De
Page 41 and 42: Chronic Granulomatous Disease 33 Di
Page 43 and 44: Chronic Granulomatous Disease 35 Tr
Page 45 and 46: Wiskott-Aldrich Syndrome 37 Definit
Page 47 and 48: Wiskott-Aldrich Syndrome 39 Maligna
Page 49: Wiskott-Aldrich Syndrome 41 Treatme
Page 53 and 54: Hyper IgM Syndrome 45 Treatment of
Page 55 and 56: DiGeorge Syndrome 47 Definition of
Page 57 and 58: DiGeorge Syndrome 49 Therapy for Di
Page 59 and 60: IgG Subclass Deficiency and Specifi
Page 61 and 62: IgG Subclass Deficiency and Specifi
Page 63 and 64: Ataxia Telangiectasia 55 Definition
Page 65 and 66: Ataxia Telangiectasia 57 General Tr
Page 67 and 68: Hyper IgE Syndrome 59 Definition of
Page 69 and 70: Hyper IgE Syndrome 61 Inheritance o
Page 71 and 72: Complement Deficiencies 63 Definiti
Page 73 and 74: Complement Deficiencies 65 Treatmen
Page 75 and 76: Other Important Primary Immunodefic
Page 77 and 78: Other Important Primary Immunodefic
Page 79 and 80: Inheritance chapter 15 Many disease
Page 81 and 82: Inheritance 73 Types of Inheritance
Page 83 and 84: Inheritance 75 Types of Inheritance
Page 85 and 86: Inheritance 77 Reproductive Options
Page 87 and 88: Laboratory Tests chapter 16 Laborat
Page 89 and 90: Laboratory Tests 81 Major Categorie
Page 91 and 92: Laboratory Tests 83 Summary Laborat
Page 93 and 94: General Care 85 General Health Meas
Page 95 and 96: General Care 87 Exercise Participat
Page 97 and 98: General Care 89 General Care During
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Specific Medical Therapy 93 Introdu
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Specific Medical Therapy 95 General
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Specific Medical Therapy 97 Hematop
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Specific Medical Therapy 99 Granulo
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Specific Medical Therapy 101 PEG-AD
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Specific Medical Therapy 103 Gene T
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Infants and Children with Primary I
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Adolescents with Primary Immunodefi
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Adults with Primary Immunodeficienc
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Health Insurance chapter 22 Having
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Health Insurance 127 Who Are the
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Health Insurance 133 LIFETIME MAXIM
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Glossary 135 Gamma globulins: The p
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Glossary 137 Sepsis: An infection o
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Reference 139 NIH Clinical Trials w
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Reference 141 International Patient
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Reference 143 Manufacturing Compani
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Reference 145 Books For Youth Balkw
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