2.4.2 Antibody Disorders (CVID and IgA Deficiency) Flashcards
What are some things that may make you suspect immunodeficiency?
§Family history
§Failure to thrive
§Need for multiple courses or IV antibiotics
§3+ sinusitis in 1 year
§2+ pneumonias in 1 decade
§4+ otitis in 1 year (depending on the age)
§2+ sepsis or meningitis
§Resistant candidiasis, abscesses, opportunistic organism, non-healing wounds
§Chronic diarrhea
§Persistent lymphopenia
§Unexplained autoimmunity
§Hypocalcemia
§Congenital heart defects
§Absence of thymic shadow on CXR
§Delayed umbilical cord detachment (30 days)
§Complication from live viral vaccination
What branch of primary immune deficiencies is most common?
Humoral immunity (B cell) deficiencies
Is primary or secondary immune deficiency more common?
Secondary
What are some causes of secondary immune deficiencies?
§Underlying disease (HIV/AIDS, DM, malignancy)
§Medications (immunosuppressives)
§Injury or Surgery
§Prematurity
§Unhealthy mother
Describe the process of B cell differentiation.
How do B cells produce different kinds of antibodies?
Class switch
Describe the process in which T cells-B cells interact with one another.
Through which process do B cells class switch? What enzyme plays an important role in this process?
Loop out DNA (IgM -> IgG -> IgE/IgA)
Enzyme: Activation induced cytidine deaminase (AID)
Which Ig molecule can cross the placenta?
IgG
Which Ig molecule is important in lining mucosa?
IgA
What is the specificity of IgE?
Binds mast cells and basophils on Fc(epsilon)RI
What are 3 different ways that B cells can go awry?
B Cell Lymphoma: too many B cells
Autoimmune B cells: attack the host
Humoral immunodeficiency: not enough Ab or nonfunctional Ab
What are some important labs when assessing a potential immunodeficiency?
CBC w/ diff, Sed Rate, Ig Levels, Ab level following vaccination, CH50 and AH50, Flow cytometry, TRECs, Leukocyte adhesion defect test, Isoagglutinins
Based on this lab, what is the patient’s possible deficiency?
§CBC with differential is normal
§ESR(sed rate): 35 mm/hr (normal <20)
§IgA: 6 mg/dL (70-390, absent if <7)
§IgM: 88 mg/dL (38-328)
§IgG: 849 mg/dL(767-1590)
IgA deficiency
Give some examples of humoral deficiencies?
§Selective IgA deficiency
§Severe combined immunodeficiency (SCID)
§Bruton’s agammaglobulinemia
§Common variable immunodeficiency (CVID)
§IgG subclass deficiency
§Selective antibody deficiency with normal immunoglobulins (SADNI)
What is the definition of selective IgA deficiency?
Complete absence of IgA in the blood serum and secretions
§Mucosal surfaces that come into contact with the environment to protect them from infection
§Mouth, ears, sinuses, nose, throat, airways, gastrointestinal tract, eyes, and genitalia
IgA reaches adult levels around puberty (KNOW THIS!)
Normal immunoglobulin levels (IgG and IgM), T cells, phagocytic cells, and complement system
What is the most common selective immunodeficiency?
Selective IgA Deficiency
What are some of the clinical features of selective IgA deficiency?
§Many appear healthy (we don’t know why)
§Susceptible to recurrent infections
§Sinopulmonary and gastrointestinal (chronic diarrhea)
§Some infections are chronic
§Some patient require longer courses of antibiotics
§Autoimmune disease (RA, SLE, ITP) – 30%
§Allergies (asthma, food allergy) – 10-15%
Why can’t blood products be given to a patient with selective IgA deficiency?
Blood products contain immunoglobulins, including IgA
When in the patient’s life can the diagnosis of IgA deficiency not be made?
Before puberty
What are the current treatment options for a patient with selective IgA deficiency?
Antibiotics (acute and prophylatic) of longer course
Allergy treatment (anti-histamines and nasal corticosteroids)
Supportive care of symptoms (possible diarrhea/AI dz)
What’s abnormal in this patient?
- CBC with differential was normal
- CMP normal
- ESR: 21 mm/hr (normal <20)
- IgA: 15 mg/dL (70-390)
- IgM: 40 mg/dL (38-328)
- IgG: 358 mg/dL (767-1590)
IgA and IgG
In CVID, what do you think will happen to the protective Ab levels upon vacination?
Little to no benefit (In the ppt, the protective serotypes for pneumococcal went from 6/23 to 7/23)
What are some defining characteristics of CVID?
-
Low levels of immunoglobulins with insufficient response to vaccinations
- Low IgG with low IgA and/or IgM levels
- Insufficient response to tetanus or pneumococcal vaccines
- Recurrent infections, some severe
When do IgG levels typically reach adult levels in patients without immunodeficiencies?
6 y/o
What are some features of the clinical presentation of CVID?
- Varies by the individual (mild to severe)
- Frequent infections
- Ears, sinuses, lungs
- Strep pneumonia, Haemophilus influenzae, and Staph
- Chronic lung damage from infections - bronchiectasis
- Scarring leading to a chronic productive cough
- Lymphoid organ enlargement
- Lymph nodes, spleen
- Autoimmune disease – autoantibody formation
- Arthritis, thyroid disease, thrombocytopenia (low platelets), anemia (low red blood cell count)
- Immune system underactive (CVID) and overactive (autoimmune disease) at the same time
- Polyarthritis without autoantibodies
- Non-infectious swelling of larger joints
- Gastrointestinal problems
- Pain, bloating, nausea, vomiting, diarrhea, malabsorption
What are some factors that can aid in the diagnosis of CVID?
Labs
- Low immunoglobulin levels
- Deficient antibody levels to vaccines
- Pneumovax, Tetanus, and/or Diptheria
- T and B cell numbers and function can be variable
Diarrhea
- Stool studies
What is the main treatment option for CVID?
Immunoglobulin replacement (IVIg or SC)
IVIg: Every four weeks
SC: weekly, less adverse effects
What are some potential side effects of immunoglobulin replacement?
Headache, flushing, chills, myalgia, wheezing, tachycardia, lower back pain, nausea, and hypotension
Anaphylaxis (especially in IgA deficiency)
What are the four subclasses of IgG. What is the definition of IgG subclass deficiency
IgG1, IgG2, IgG3, IgG4
One or more is low but the total IgG is normal
What is the function of IgG1 and IgG3? IgG2?
IgG1 and IgG3: fight toxins produced by bacteria and viruses
IgG2: encapsulated bacteria (pneumococcus and haemophilus influenzae)
What is the most common IgG subclass deficiency in children? Adults?
Circulating IgG – varies with age
IgG1 – 60-70%, rarest deficiency
IgG2 – 20-30%, most frequent deficiency in children
IgG3 – 5-8%, most frequent deficiency in adults
IgG4 – 1-3%, most with IgG2 deficiency (>10 years)
What is SADNI?
Specific Antibody Deficiency with Normal Immunoglobulins
Common features of SADNI?
Normal IgG subclass and total IgG levels
Inadequate antibody response to vaccines evaluated at least 4 weeks after vaccination
