Combined b-cell and t-cell deficiencies Notes

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Adenosine deaminase deficiency

Severe combined immunodeficiency

Chapter 2 Acyanotic Defects NOTES COMBINED B-CELL & T-CELL DEFICIENCIES GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Group of disorders characterized by impaired cellular, humoral immunity ▪ Diverse genetic causes ▪ Leads to immunodeficiency, increased susceptibility to recurrent, potentially fatal infections SIGNS & SYMPTOMS ▪ Recurrent infections, chronic diarrhea, failure to thrive (FTT), skin rashes DIAGNOSIS LAB RESULTS ▪ Low T lymphocyte, natural killer (NK) cell count ▪ Normal B lymphocyte count, low immunoglobulins ▪ Genetic testing to find defect TREATMENT OTHER INTERVENTIONS ▪ Measures to prevent serious infections (e.g. antimicrobial prophylaxis, isolation) Hematopoietic stem cell transplantation (HSCT) ▪ If HSCT fails ▫ Genetic therapy ADENOSINE DEAMINASE DEFICIENCY osms.it/adenosine-deaminase-deficiency PATHOLOGY & CAUSES ▪ Absence of ADA → intracellular accumulation of metabolites (e.g. deoxyadenosine), toxic to lymphocytes (esp. T cells) ▪ Reduction of T, B lymphocytes, NK cell count → combined immunodeficiency ▪ Autosomal recessive pattern of inheritance COMPLICATIONS ▪ Progresses to severe combined immunodeficiency (SCID) SIGNS & SYMPTOMS ▪ Presents as SCID early in life ▪ Neurologic abnormalities (cognitive deficits, behavioral problems, gait abnormalities) OSMOSIS.ORG 187
DIAGNOSIS TREATMENT OTHER INTERVENTIONS LAB RESULTS ▪ Measures to prevent infections, HSCT ▪ Gene therapy, enzyme replacement therapy (less effective) ▪ SCID ▫ Decreased ADA blood levels OTHER DIAGNOSTICS ▪ Genetic testing SEVERE COMBINED IMMUNODEFICIENCY (SCID) osms.it/SCID PATHOLOGY & CAUSES ▪ Rare genetic syndrome; disturbance in cellmediated, humoral immunity ▪ Combined defects in T, B lymphocyte development, function → severe immunodeficiency CAUSES ▪ Underlying causes vary in different forms of SCID ▪ Cytokine receptor defects, adenosine deaminase (ADA) deficiency (most common) ▪ Cytokine receptor defects (50–60% of cases) ▫ Mutation in gene encoding common γ-chain subunit of interleukin (IL) receptors (IL-2 receptor gamma/IL-2Rγ) ▪ Impaired interleukin signaling required for survival, development, proliferation of lymphocytes (esp. T lymphocytes) ▪ Profound decrease in lymphocyte count (esp. T, NK-cells) ▪ B lymphocyte count can be normal, immunoglobulin synthesis defective due to lack of T helper cells 188 OSMOSIS.ORG RISK FACTORS ▪ X-linked recessive pattern of inheritance, more common in individuals who are biologically male COMPLICATIONS ▪ Susceptibility to recurrent, severe infections by wide range of microorganisms ▫ Candida albicans, Pneumocystis jiroveci, Pseudomonas, cytomegalovirus, varicella ▪ Without HSCT, death may occur within first year due to fatal infections SIGNS & SYMPTOMS ▪ Recurrent infections ▪ Oral candidiasis presenting with prominent thrush ▪ Chronic diarrhea → malabsorption, failure to thrive ▪ Extensive rash ▪ Morbilliform rash due to reaction of maternal T cells against fetus → graft versus host disease (GVHD)
Chapter 30 Combined B-Cell & T-Cell Deficiencies DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray ▪ Hypoplasia of lymphoid tissues ▫ Absence of thymic shadow; thymic hypoplasia LAB RESULTS ▪ Complete blood count (CBC), manual differential ▫ Total lymphocyte count, ↓ T cell count, normal B cell count, ↓ immunoglobulin levels ▪ Polymerase chain reaction (PCR) ▫ Measure concentration of T cell receptor excision circles (TRECs); indicative of T cell maturation → decreased levels in SCID ▪ Genetic testing to find the specific defect ▪ Lymph node biopsy ▫ Hypoplasia of lymphoid tissues where lymphocytes develop ▫ Absence of germinal centers TREATMENT OTHER INTERVENTIONS Prevention ▪ Isolation to prevent serious infections; “bubble baby disease” ▪ Avoidance of live vaccines ▪ Antimicrobial prophylaxis ▪ Immunoglobulin replacement therapy HSCT ▪ Curative therapy for most cases ▪ If HSCT fails ▫ Genetic therapy (less effective) OSMOSIS.ORG 189

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