Lymphopenia, Constitutional and Acquired



Lymphopenia, Constitutional and Acquired


Qian-Yun Zhang, MD, PhD









This peripheral blood smear from a patient with severe combined immunodeficiency shows pancytopenia, anisopoikilocytosis, and polychromasia of the red blood cells. A single neutrophil is seen in this microphotograph.






This peripheral blood smear from a patient with severe combined immunodeficiency status post bone marrow transplantation reveals normal CBC and differential counts.


TERMINOLOGY


Synonyms



  • Lymphocytopenia


Definitions



  • Absolute lymphocyte count < 1,000/µL in adults or < 2,000/µL in children


ETIOLOGY/PATHOGENESIS


Congenital Immunodeficiency Disorders



  • Severe combined immunodeficiency disease (SCID)



    • Immunodeficiency with defects in both humoral and cell-mediated immunity


    • Pathogenesis



      • Impaired precursor survival due to mutations in adenylate kinase 2 gene or deficiency of adenosine deaminase


      • Defects in cytokine-mediated signaling due to mutations in IL-2 receptor gamma gene or IL-7 receptor gene


      • Deficiency of the common gamma chain of T-cell growth factor receptor and other growth factor receptors


      • Defect in immune recognition receptors on T- and B-cells due to mutations in RAG1, RAG2 genes


      • Defects in CD3 development due to mutations CD3 complex genes


      • Defects in T-cell development/signaling due to ZAP70 or STAT5B gene mutations, or major histocompatibility complex (MHC) class II deficiency


  • DiGeorge syndrome (DGS)



    • Results from deletion of chromosome 22q11.2


    • Transcription factor gene TBX1 may be responsible at molecular level


    • Malformation of 3rd and 4th pharyngeal pouches, which give rise to thymus, parathyroid glands, part of aortic arch and face


    • 22q11.2 deletion may also give rise to velocardiofacial syndrome, with congenital heart diseases as major manifestations


Idiopathic CD4 T-lymphocytopenia (ICL)



  • Unknown etiology; may represent various disorders and is likely multifactorial



    • Diminished generation of T-cell precursors


    • Increased T-cell apoptosis


    • Failure of T-cell development


    • Defective cytokine production


    • CD4 autoantibody


Acquired Immunodeficiency Disorders



  • HIV infection/AIDS causes lymphopenia by several mechanisms



    • Transmitted through sexual or parental exposure to HIV-containing fluids or maternal-fetal transmission


    • HIV viruses cause destruction of CD4(+) lymphocytes


    • HIV-mediated destruction of mucosal barriers


    • Damage of thymus and other lymphoid tissues


  • Other viral infections


  • Bacterial infections


  • Systemic disorders linked to lymphopenia via diverse mechanisms



    • Nutritional deficiencies


    • Protein-losing disease; GI or renal diseases, burns


    • Malignancy


  • Autoimmune disorders are linked to lymphopenia as consequence of self-destruction


  • Therapy causes lymphocyte destruction



    • Radiation/chemotherapy


    • Antilymphocyte globulin



CLINICAL ISSUES


Epidemiology



  • Incidence



    • SCID is rare; X-linked or autosomal recessive inheritance


    • DGS affects 1 in 2,000-4,000 live births


    • Idiopathic CD4 lymphocytopenia (ICL) is rare; can be seen in any age


    • HIV infection is most common cause of sustained lymphopenia

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Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Lymphopenia, Constitutional and Acquired
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