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.



  • Lymphocytopenia


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


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



  • 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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