First Aid, Chapter 8, Immunologic Disorders, SCID Flashcards
What is the lymphocyte phenotype in X-linked SCID caused by the mutation in the γc chain?
T–B+NK–
Which type of SCID can most easily be missed by newborn TRECs (Tcell receptor excision circles) screening?
ADA deficiency
What is the most common form of SCID? Who is most often diagnosed?
X-linked SCID (γc chain defect) and, therefore, most cases will be diagnosed in male infants.
What type of SCIDs experience the following infections/clinical findings: FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections?
X-linked SCID (yc chain), AR SCID (JAK-d deficiency, IL-7Ra (CD127), IL-2Ra (CD25), CD45, CD3δεζ, RAG 1/2
What are the infections/clinical findings in X-linked SCID (yc chain)?
FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections
What are the infections/clinical findings in JAK-3 deficiency?
FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections
What are the infections/clinical findings in IL-7Rα (CD127)?
FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections
What are the infections/clinical findings in IL-2Rα (CD25)?
FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections
What are the infections/clinical findings in CD45?
FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections
What are the infections/clinical findings in CD3δεζ?
FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections
What are the infections/clinical findings in RAG1/2?
FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections
Why do JAK-3 deficiency and yc chain SCID have the same phenotype?
JAK-3 is a signaling protein of γc chain, therefore both have the same phenotype
What cytokine signalling defects is yc chain SCID involved in?
γc chain involves in IL-2, 4, 7, 9, 15, 21 receptor signaling
Why is IL-7Ra SCID B+N+?
IL-7Rα is specific for only T-cell development
Why are CD45 and CD3δεζ SCID B+NK+?
CD45 tyrosine phosphatase and CD3 subunits involve in only TCR signaling, therefore B+ NK+
Why are RAG 1/2 SCID NK+?
RAG1/2 involves in VDR rearrangement of T- and B-cell Ag receptor formation, therefore NK+.
(Proteins are unique to immune cells, no radiation sensitivity)
What gene is defective in yc x-linked SCID? What is the lymphocyte phenotype?
IL-2RG
T-B+NK-
What gene is defective in JAK-3 deficiency SCID? What is the lymphocyte phenotype?
Gene: JAK-3
Lymphocyte phenotype: T-B+NK-
What gene is defective in IL-7Ra(CD127) SCID? What is the lymphocyte phenotype?
Gene: IL-7Ra
Lymphocyte phenotype: T-B+NK+
What gene is defective in IL-2Ra(CD25) SCID? What is the lymphocyte phenotype?
Gene: IL-2Ra
Lymphocyte phenotype: T-B+NK+
What gene is defective in CD45 SCID? What is the lymphocyte phenotype?
Gene: CD45
Lymphocyte phenotype: T-B+NK+
What gene is defective in CD3δεζ SCID? What is the lymphocyte phenotype?
Gene: CD3δεζ
Lymphocyte phenotype: T-B+NK+
What gene is defective in RAG 1/2 SCID? What is the lymphocyte phenotype?
Gene: RAG 1/2
Lymphocyte phenotype: T-B-NK+
What is the inheritance of Omenn’s syndrome? What are the infections/clinical manifestations?
Autosomal Recessive
Infections/Clinical findings:
rythroderma, increased lymphoid tissues, alopecia, recurrent infections, eosinophilia, high IgE
What are the defects in Omenn’s syndrome?
Hypomorphic defects in RAG1/2. Also IL-7RA, ADA, Artemis, RNA component of RNAse mitochondrial RNA, and leaky phenotype
What is the gene that is defective in Omenn’s syndrome?
Gene: RAG 1/2
What is the lymphocyte phenotype of Omenn’s syndrome?
B-NK+
T lymphocytes in Omenn’s are oligoclonal, CD45RO+, and TREC–.
What are the clinical findings and infections in ADA deficiency SCID?
Skeletal abnormalities: “rachitic rosary” ribcage and abnormal iliac bone, deafness
What is the lymphocyte phenotype in ADA deficiency SCID?
T-B-NK-
What is the defect in ADA deficiency SCID?
Premature lymphoid progenitor cell death from accumulating toxic metabolites, therefore all negative phenotypes.
(Defective nucleotide salvage pathway) (Defective purine nucleotide metabolism) (Defective hematopoietic energy metabolism)
What are the clinical findings and infections in PNP deficiency SCID?
Lymphoreticular disease and autoimmune disease
What is the lymphocyte phenotype in PNP deficiency SCID?
T-B+NK+/-
What are the clinical findings and infections in reticular dysgenesis SCID?
Severe neutropenia and sensorineural deafness
What is the lymphocyte phenotype in reticular dysgenesis SCID?
T-B-NK-
What kinds of infections/clinical findings occur in artemis SCID?
Diarrhea and candidiasis Athebascan-speaking Navajo/Apache
What is the defect in artemis SCID?
- Recombinase DNA repair protein defect
- Defective receptor formation
What is the gene involved in artemis SCID?
artemis
What is the lymphocyte phenotype in artemis SCID?
T-B-NK+
What are the radiosensitive SCIDs?
Artemis, Cernunnon, Ligase IV, Nijimegen breakage syndrome
What are the infections/clinical findings in cernunnos SCID?
Developmental delay, growth failure, and bird-like facies
Microcephaly
What is the defect in cernunnos SCID?
Recombinase DNA repair protein defect Hypogammaglobulinemia
What is the gene that is defective in Cernunnos SCID?
Cernunnos
What is the lymphocyte phenotype in cernunnos SCID?
T-B-NK+
What are the infections/clinical findings in ligase IV SCID?
Developmental delay, FTT, Bird-like facies Microcephaly, photosensitivity Pancytopenia and malignancy
What is the defect in ligase IV SCID?
Recombinase DNA repair protein defect
Pancytopenia
↓CD4/CD8
What is the gene that is defective in ligase IV SCID?
Ligase IV
What is the lymphocyte phenotype of ligase IV SCID?
T-B-NK+
What are the infections/clinical findings in Nijimegen breakage syndrome?
Microcephaly, recurrent infections, bird-like facies, developmental delay, lymphoma, short stature, clinodactyly,syndactyly, and radiatiosensitive
What is the defect in Nijimegen breakage syndrome?
Class switching recombination defect ↓CD4/CD8
↓proliferation
Can have hypogammaglobulinemia and IgA deficiency.
Elevated IgM
Defect in specific antibody response
Absence of Hassel’s corpuscles on thymic biopsy
What is the gene in Nijimegen breakage syndrome?
NBS1 (substrate for ATM)
What is the lymphocyte phenotype in Nijimegen breakage syndrome SCID?
T-B-NK+
What is the treatment of SCID?
- Preventing infections with intravenous immunoglobulin (IVIG), prophylactic antibiotics (sulfamethoxazole/trimethoprim), antifungals, withholding live immunizations, and isolation in the sterile environment
- Improving nutritional status
- Hematopoietic stem cell transplantation
- Gene therapy
- Enzyme replacement; pegdemase bovine ADA (ADA-PEG)
- Avoid breast feeding
- CMV negative, irradiated blood products
What conditions cause CD8 lymphopenia? CD4 lymphopenia?
- CD 8 lymphopenia can be caused by MHC class I deficiency (TAP1/2 deficiencies, tapasin deficiency) and ZAP70 deficiency (lack of blood CD8 lymphocyte).
- CD4 lymphopenia can be caused by bare lymphocyte syndrome (MHC class II deficiency), LCK deficiency, and HIV infection.
