Primary Immunodeficiencies, etc. 2% Flashcards
A 3-year-old boy has had numerous bacterial infections, including respiratory infections with Hemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus since infancy. He develops a polyarthritis that clears with immunoglobulin therapy. A lymph node biopsy is performed, and microscopically the germinal centers of his nodes are rudimentary. During the 3rd decade of his life he develops systemic lupus erythematosus. He demonstrates skin test positivity to Candida antigen. Laboratory studies show that his serum IgG is 110 mg/dL. His total WBC count is 7650/microliter with differential count of 65 segs, 4 bands, 22 lymphs, and 9 monos.
Which of the following immunologic disorders best explains these findings?
A Adenosine deaminase deficiency
B Malformation of 3rd and 4th pharyngeal pouches
C Reduction in CD4 lymphocytes
D A defect of NADPH oxidase
E Failure of B cell maturation into plasma cells
E. Failure of Be cell maturation
He has features of X-linked agammaglobulinemia of Bruton. BTK enzyme mutation. In this condition, B-cell maturation stops after the rearrangement of heavy-chain genes, and light chains are not produced. Thus, complete immunoglobulin molecules with both heavy and light chains are not assembled and transported to the cell membrane. The lack of immunoglobulins predisposes the child to recurrent bacterial infections. Since T-cell function remains intact, viral, fungal, and protozoal infections are not common. IgGAME is all low.
A 5-year-old male who has recurrent URIs but is otherwise healthy presents with 5 days of fever, bilateral conjunctivitis, strawberry tongue, a 2-cm cervical LN, maculopapular rash, extremity swelling, and extreme irritability. He is admitted to the hospital and treated with the first line treatment for this condition. He develops a severe transfusion reaction. What underlying condition does he have that makes him susceptible to severe transfusion reactions to the treatment?
IgA deficiency
Individuals with absent IgA are susceptible to severe transfusion reactions caused by anti-IgA Ab
A 14-year-old patient with a history of recurrent AOM and pneumonia was found to have low IgG. He is evaluated by the immunologist and was found to have low B cells. What is the condition?
Common variable immunodeficiency - associated with defects in both cellular and humora immunity
A 7-year-old male with eczema is admitted to the hospital with his 4th bout of pneumonia. On labs, he has a leukocytosis, thrombocytosis, neutrophilia, and eosinophilia. What immunodeficiency should be on the differential? What are the associated gene mutations?
Hyper IgE syndrome
STAT3 (AD, Job syndrome)
DOCK8 (AR)
What autoimmune conditions are associated with children with CVID?
Atrophic gastritis Evans syndrome IBD JIA Lymphoid interstiital pneumonia Pernicious anemia
An 18-month-old female presents with fever, pallor, fatigue, and listlessness and was found to have a Hgb of 6.8. DAT+, LDH and bilirubin elevated, haptoglobin low. On exam, she has extensive lymphadenopathy. Bone marrow biopsy negative for malignancy. LN biopsy with reactive follicular hyperplasia. Flow cytometry reveals elevated CD4-CD8- T cells. What is the diagnosis and what are some gene mutations associated with the condition?
Autoimmune Lymphoproliferative Syndrome
Somatic or. germline pathogenic mutation in FAS, FAS ligand, or CASP10
A 3-month old with eczema and failure to thrive was found to have a markedly elevated fecal calprotectin. He also has features of type 1 diabetes mellitus, autoimmune hemolytic anemia, hypothyroidism, and nephropathy. What laboratory study may confirm the diagnosis?
Immunodysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome (IPEX
Genetic testing for a mutation in FOXP3 gene, which encodes the transcription factor required for Treg development
A young child is admitted for severe fatigue, poor weight gain, nausea, vomiting, diarrhea, abdominal pain, and myalgias. He was found to be hypotensive and hypoglycemic. He has a history of persistent oral Candidiasis. During his evaluation, he is found to have hypoparathyroidism. What condition should be suspected, and what laboratory study may confirm the diagnosis?
Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) aka
Autoimmune Polyendocrinopathy Syndrome (APS-1)
Due to AR mutation in autoimmune regular (AIRE) gene), which encodes a trancription factor essential for intrathymic central tolerance (negative selection of self-reactive T cells
May present with Sjogren syndrome!
A 5-year-old boy is admitted with his third episode of bacterial meningitis. Each time a culture from his cerebrospinal fluid has grown Neisseria meningitidis.
What is the BEST test to find the underlying immune deficiency responsible for his recurrent infections?
CH50
Deficiencies of terminal complement components (C5-C9) often present this way.
The best single routine laboratory test for measuring classical complement system function is CH50, which would be low in patients with complement deficiencies in C5 to C9.
What test screens for chronic granulomatous disease?
Neutrophil oxidative burst or nitroblue tetrazolium test (NBT) or dihydrorhodamine assay
What part of the immune system are you evaluating when you do antibody testing in response to vaccines?
B-cell function
How do you test T cell function?
Stimulation of lymphocytes with a mitogen, such as phytohemagglutinin, is a method to evaluate T-cell function
What is CGD?
How is it inherited? Gene mutations?
What are the most common pathogens involved in causing infections?
Chronic Granulomatous Disease
- Develop infections in lungs, skin, lymph nodes, liver, stomach, intestines
- x-linked (2/3 of cases) - more severe, GP91-phox mutation
- autosomal recessive (1/3 of cases) - GP47-phox, GP67-phox, GP22-phox, GP40-phox mutations
Common pathogens:
- Staph aureus
- Burkholderia
- Serratia
- Nocardia
- Aspergillus
- Candida
- Tricosporon
Bonus:
Susceptible to catalase POSITIVE organisms like Staphylococci and Micrococci. Other catalase positive organisms - Listeria, Corynebacterium diphtheriae, Burkholderia cepacia, Nocardia, the family Enterobacteriaceae (Citrobacter, E. coli, Enterobacter, Klebsiella, Shigella, Yersinia, Proteus, Salmonella, Serratia), Pseudomonas, Mycobacterium tuberculosis, Aspergillus, Cryptococcus, and Rhodococcus equi.
What gene mutation is associated with profound lymphopenia with absent T cells, B cells, and NK cells?
SCID
Gene mutation in adenosine deaminase (ADA) or adenylate kinase 2
What disease is caused by mutations in FOXP3?
immune-mediated polyendocrinopathy, X-linked (IPEX)
Deleterious mutations in FOXP3, which is located on the X chromosome, cause IPEX. FOXP3 encodes a transcription factor critical for the development and differentiation of regulatory T cells (Tregs). Based on their expression of FOXP3 as well as their high surface expression of CD25, Tregs maintain peripheral tolerance by dampening the inflammatory responses of effector T cells. Deficiency of Tregs in IPEX leads to a syndrome of early onset enteropathy, endocrinopathy, and eczema
