Immunodeficiency Flashcards
What are the defects in recurrent/chronic pyogenic infections?
Antibodies B cells Complement Phagocytes Mostly caused by encapsulated bacteria
What are the defects of opportunistic infections or cancer?
T cell alone or combined
Mostly caused by viruses, fungi and parasites
Live viral vaccines are contraindicated (MMR,VAR,ZOSTERVAX,LAIV)
What is the most common primary immunodeficiency?
Selective IgA
Affected mostly caucasians
What is the treatment of primary B cell?
Control infections with antimicrobials
Immunoglobulin (IG) replacement therapy
Do not treat IgA deficiency with replacement IG
What are the B cell and antibody deficiencies that are X linked?
X linked (Bruton’s) agammaglobulinemia X linked Hyper-IgM syndrome
What are the B cell and antibody deficiencies that are autosomal?
Transient hypogammaglobulinemia of infancy
Selective IgA deficiency
Selective IgM or IgG subclass deficiencies
Common variable immunodeficiency
Autosomal Hyper-IgM syndrome
What is the presentation of X linked Agammaglobulinemia (XLA)?
Affects males only
Onset between 3 months and 3 years
Repeated pyogenic bacterial infections not responding to antibiotics
Bronchiectasis is a common cause of death
Caused by defect of BTK gene
How to diagnose XLA?
Near absence of all antibody classes
No ABO isohemagglutinins
Near absence CD19+ B cells in blood
BTK gene defect is confirmatory
What is the presentation of selective IgA deficiency?
Many remain asymptomatic
Symptomatic patients present with celiac disease, autoimmunity such as RA, SLE
May progress to CVID
May possess IgE directed toward IgA
How is selective IgA deficiency diagnosed?
Serum IgA<5-7 mg/dL
Normal IgG and IgM
How is selective IgA deficiency treated?
Antimicrobials
No IVIG or SCIG
What is the presentation of IgM and IgG2 deficiencies?
Can’t respond to polysaccharide capsules on bugs or in vaccines
Agressive use of antibiotics for treatment of recurrent respiratory tract infections
Replacement IG is controversial
What is the presentation of Transient Hypogammaglobulinemia of Infancy (THI)?
Period of hypogammaglobulinemia more severe and more prolonged beyond 6 months
Correct itself by age 3
B or TH presenting as antibody deficiency
How is THI diagnosed?
Serum IgG low>2SD below norm
IgM or IgA normal or low
How is THI treated?
Antimicrobials as needed
Delay live vaccines shot
IG not usually given
What is the presentation of Common Variable Immunodeficiency (CVID)?
Affect both sexes
Usually after age 4, typically in 30s
May follow EBV infection
May follow selective IgA deficiency
Increase incidence of giardia
Mothers cannot confer passive protection on infants
Caused by B cells not developing into plasma cells—-> low serum antibodies
How is CVID diagnosed?
Low CD27+
Normal CD19+CD20+
Treated with antimicrobials, IG replacement
What are the characteristics of Hyper-IgM syndrome?
Patients present with recurrent respiratory infections beginning at 1-2 years
Inability to switch from production of IgM to other isotypes
X linked is 70% of the cases
Diagnosed by reduced IgG, IgA, elevated or normal IgE
How is Hyper-IgM treated?
Antibiotics
Replacement IG
Stem cell transplant
What are the X linked T cell deficiency?
X linked SCID
Wiskott-Aldrich syndrome (WAS)
What are the autosomal T cell deficiencies?
Autosomal SCID Omenn syndrome Bare lymphocyte syndrome Ataxia telangiectasia Hyper IgE syndrome DiGeorge syndrome Chronic mucocutaneous candidiasis
What are the characteristics of SCID?
Heterogenous disorder with defects in both CMI and antibody production
Fatal by age 1 if not treated
Patients are susceptible to all types of infection: CMV,C.albicans
Vaccination with live microbes is lethal
Symptoms occur earlier than in XLA
What is the treatment of SCID?
Antimicrobials
Stem cell transplant
What are the 4 phenotypes of SCID?
T-B+
T-B-
T+B-
T+B+
What are the diseases associated with T-B+ phenotype?
Common gamma chain deficiency- defect in IL-2,4,17,9 and 15- NK absent
JAK3 tyrosine kinase deficiency- NK absent
IL-7R alpha chain deficiency
PNP deficiency- mental retardation
What are the diseases associated with T-B- group?
ADA deficiency
Recombinase deficiencies with radio sensitivity- mutations in RAG-1 and 2-no T, no B, no antibodies
What are the characteristics of Omenn syndrome?
Associated with T+B- Leaky SCID with partial RAG activity Low T and B numbers No pathogen specific immunity Resembles a graft versus host reaction Hyper IgE production Malnutrition from protein loss Treated with stem cell transplant, IFN gamma, cyclosporine
What are the characteristics of Bare lymphocyte syndrome (BLS)?
Cells lack MHC 1, 2 or both
No collaboration between APCs and T cells
In class 1 deficiency, TAP molecules are to blame—> HLA 1 not expressed on cell surface
Defect in ZAP 70 and CD3
TREC assay for newborns-SCID<25 copies
What is the presentation of Hereditary Ataxia Telangiectasia?
Neurologic, immunologic, endocrine, hepatic and cutaneous abnormalities
Ataxia by age 18 months due to degeneration of Purkinje cells
Telangiectasia ( dilated capillaries) on skin and in eyes by 6 years
Defect in ATM gene
How is Hereditary Ataxia Telangiectasia diagnosed?
Elevated AFP and CEA
Inversions and translocations of chromosomes 7 and 14
Absent adenoids, small or absent thymic shadow
Lymphadenopathy suggests lymphoma
How is Hereditary Ataxia Telangiectasia treated?
Antibiotics
IVIG
Death from bronchopulmonary infection or malignancy by early to middle adolescence
What are the characteristics of Wiskott Aldrich Syndrome (WAS)?
X linked presents in males at 20 months
Classic triad: bleeding/ thrombocytopenia,recurrent bacterial infections, allergic reactions
Caused by defect in gene coding for WASP
How is WAS diagnosed?
Low platelets (70,000/microliters)
High serum IgE
Normal/high IgA
Low IgM and IgG
What is the treatment for WAS?
Antimicrobials as needed
Prophylactic IVIG
Platelet or blood transfusions for bleeding
Treat eczema with creams and topical steroids
Avoid food allergens
Bone marrow transplant
What are the characteristics of Job Syndrome (Hyper IgE)?
Affects multiple organs Recurrent cold staphylococcal abscesses Elevated IgE No bleeding disorders Retained primary teeth Autosomal dominant due to defect in STAT3
How is Job syndrome diagnosed ?
Serum IgE at least 2 SD above upper limit of normal
Clinical features
Eosinophilia with normal lymphocytes
How to treat Job syndrome?
Prophylactic antibiotics to prevent staph and Candida infections
What are the characteristics of congenital thymic aplasia aka DiGeorge syndrome?
Thymus and parathyroids do not form from the 3rd and 4th pharyngeal pouches
Few or no T cells
Hypocalcemic tetany in the first 24 hours of life
Shortened philtrum of upper lip
Due to sporadic 22q11.2 deletion
How is DiGeorge diagnosed?
Thymic shadow absent or reduced
B cell present but no T dependent IgG production
No live vaccines
How is DiGeorge treated?
Antimicrobials
Bone marrow transplant
What are the characteristics of chronic mucocutaneous candidiasis ?
Oral thrush and/or skin infections
Diaper rash
Can also affect the nails
Due to overgrowth of Candida albicans
Interference with IL-17 production or signaling
Mutation in STAT1 is autosomal dominant
Mutations in CARD9 and IL-17RC are autosomal recessive
How is chronic mucocutaneous candidiasis diagnosed and treated?
Candida in skin scrapings growth on culture media
Candida antigens: negative skin testing
Treated with antifungal agents
What are the diseases associated with phagocytic deficiencies ?
Chronic granulomatous disease (CGD)- X linked and autosomal
Leukocyte Adhesion Deficiency (LAD)1 and 2
Chediak-Higashi syndrome
Mendelian susceptibility to mycobacterial disease
What are the characteristics of CGD?
Present by age 2 , most common in males Repeated infections by catalase positive bacteria (staph) and fungi (aspergillus) Lymphadenitis Abscess in skin, liver and viscera Due to lack of functional NADPH oxidase X linked:gp91phox subunit
How is CGD diagnosed and treated?
DHR test- if positive no CGD
NBT reduction test- if positive no CGD
Treated with antimicrobials, IFN gamma, bone marrow transplant
What are the characteristics of LAD 1?
Missing adhesions molecules leading to inability of leukocytes to extravasate
Cannot form pus efficiently
Impaired wound healing
Defect in CD18
Absent LFA-1 phagocytes cannot adhere to ICAM-1
How is LAD1 diagnosed and treated?
Leukocytosis regardless of infection status
Treated w antibiotics to active infection, bone marrow or stem cell transplant
What are the characteristics of LAD2?
Infections
Growth and mental retardation
Due to defect in fucose metabolism
Lack of CD15/ sialyl Lewis X
How is LAD2 diagnosed and treated?
Flow cytometry for CD 15
Treated with antibiotics for active infection, fucose replacement therapy
What are the characteristics of Chediak-Higashi disease?
Recurrent skin, lung , respiratory tract infections Oculocutaneous albinism Progressive cognitive decline Due to LYST gene NK & Tc activity depressed
How is Chediak Higashi disease diagnosed and treated ?
Giant granules in granulocytes apparent on stained blood smears
Treated by antibiotics, anti virals
BMT- in accelerated phase
Poor prognosis
What are the characteristics of Mendelian Susceptibility to Mycobacterial Disease (MSMD)?
Susceptibility to infection with weakly pathogenic bacteria , virus and salmonella infections
No administration of BCG vaccine
Recessive mutations in genes coding for one or more proteins : STAT1 transcription factor,integrin beta 1,
How is MSMD diagnosed and treated?
Test for STAT1
IFN gamma serum cytokine
Treated with antibiotics
Adding IFN gamma wont help with total IFN gamma receptor
What are the diseases associated with complement deficiencies ?
C1,C2,C4–>SLE C3—>encapsulated bacteria C5-C9—-> Neisseria Properdin—>Neisseria C1INH—-> HAE GPI—-> paroxysmal nocturnal hemoglobinuria
What are the characteristics of HAE?
Edema of hands, face, arms
Laryngeal edema
Edema preceded by tingling and erythema
Edema caused by stress or trauma( dental procedure)
What are the 3 types of HAE?
Type 1- low levels of C1INH
Type 2- dysfunctional C1INH
Type 3- Normal C1INH, factor 12 gene mutation
Treated with C1INH replacement therapy or fresh frozen plasma
What are the characteristics of paroxysmal nocturnal hemoglobinuria (PNH)?
Dark urine due to RBC lysis
Triad of anemia, pancytopenia, thrombosis in large vessels
Budd- Chiari syndrome: abdominal pain, ascites, enlarged liver
Severe headaches and eye
Defect in GPI anchors for DAF (CD55) and HRF (CD59)
How is PNH diagnosed?
Median age is 42 with survival of 10 years
CBC with differential
Treated with prednisone or eculizumab (Mab toC5)
