Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + CLASSIFICATION Download Section PDF Listen +++ ++ Polyclonal lymphocyte and plasma cell disorders can be classified into two major groups (Table 49–1): — Primary disorders that result from defects intrinsic to B lymphocytes (e.g., X-linked agammaglobulinemia), T lymphocytes (e.g., congenital thymic aplasia), and/or natural killer cells, the latter usually coupled with a B or T cell deficiency (e.g., interleukin (IL)-7 receptor α-chain deficiency) (see Chap. 51). — Acquired disorders that result from physiologic or pathophysiologic responses to extrinsic factors, usually infectious agents (e.g., Epstein-Barr virus or human immunodeficiency virus infection). (See Chaps. 50, 52, 53.) The monoclonal lymphoid disorders are classified in Chap. 54 and individual neoplastic lymphoid diseases are described in Chaps. 55–72. — Disparate disorders can have similar clinical manifestations, such as recurrent infections as a result of either B or T cell deficiency. Lymphocyte disorders can have clinical manifestations that are not restricted to cells of the immune system (e.g., leprosy or systemic lupus erythematosus). In some cases, classification is influenced by disease manifestations: — Diseases caused by production of pathologic autoantibodies; e.g., autoimmune hemolytic disease (see Chaps. 24–26), autoimmune thrombocytopenia (see Chap. 120), and systemic autoimmune diseases (e.g., myasthenia gravis). — Diseases caused by excess production of lymphocyte cytokines; e.g., chronic inflammatory disorders. ++Table Graphic Jump LocationTABLE 49–1CLASSIFICATION OF NON-CLONAL DISORDERS OF LYMPHOCYTES AND PLASMA CELLSView Table||Download (.pdf) TABLE 49–1 CLASSIFICATION OF NON-CLONAL DISORDERS OF LYMPHOCYTES AND PLASMA CELLS Primary disorders* B-lymphocyte deficiency or dysfunction Agammaglobulinemia Acquired agammaglobulinemia Associated with celiac disease X-linked agammaglobulinemia of Bruton Selective agammaglobulinemia IgM deficiency (1) Bloom syndrome (2) Isolated (3) Wiskott-Aldrich syndrome Selective IgG deficiency IgA deficiency (1) Isolated asymptomatic (2) Steatorrheic IgA and IgM deficiency Hyper-IgA Hyper-IgD Hyper-IgE Hyper-IgE associated with HIV infection Hyper-IgM immunodeficiency X-linked lymphoproliferative disease T-lymphocyte deficiency or dysfunction Cartilage-hair hypoplasia Lymphocyte function antigen-1 deficiency Thymic aplasia (DiGeorge syndrome) Thymic dysplasia (Nezelof syndrome) Thymic hypoplasia Wiskott-Aldrich syndrome ZAP-70 deficiency Purine nucleoside phosphorylase deficiency Interleukin-7 receptor deficiency Major histocompatibility complex class I deficiency Coronin-1A deficiency IPEX syndrome caused by mutations in FoxP3 that cause a deficiency of CD4+ regulatory T cells (Tregs) APECED syndrome caused by mutations in the autoimmune regulator gene (AIRE) gene Autoimmune lymphoproliferative syndrome Calcium entry channel deficiency caused by mutations in ORAI1 or STIM1 Combined T- and B-cell deficiency or dysfunction Ataxia-telangiectasia Combined immunodeficiency syndrome Adenosine deaminase deficiency Thymic alymphoplasia Major histocompatibility complex class II deficiency—bare lymphocyte syndrome IgG and IgA deficiency and impaired cellular immunity (type I dysgammaglobulinemia) Immunodeficiency with thymoma Pyridoxine deficiency Reticular agenesis (congenital aleukocytosis) Omenn syndrome WHIM syndrome resulting from mutation in the CXCR4 gene Nijmegen breakage syndrome Acquired disorders Acquired immunodeficiency syndrome Reactive lymphocytosis or plasmacytosis Bordetella pertussis lymphocytosis Cytomegalovirus mononucleosis Drug-induced lymphocytosis Epstein-Barr virus mononucleosis Inflammatory (secondary) plasmacytosis of marrow Other viral mononucleosis Polyclonal lymphocytosis Serum sickness Toxoplasma gondii mononucleosis Viral infectious lymphocytosis T-lymphocyte dysfunction or depletion associated with systemic disease Leprosy Lupus erythematosus Sjögren syndrome Sarcoidosis *Further details of primary (inherited or congenital) immunodeficiency diseases can be found in Chap. 51, Primary Immunodeficiency Syndromes.Source: Williams Hematology, 8th ed, Table 80–1, p. 1138. + CLINICAL MANIFESTATIONS Download Section PDF Listen +++ +++ B-Lymphocyte Disorders ++ Infection with any class of microorganism (e.g., bacteria, viruses, fungi) as a result of immunoglobulin deficiency and impaired opsonization and clearance of pathogen. Tissue or organ abnormality as a result of pathogenic autoantibodies (e.g., immune hemolytic anemia, immune thrombocytopenia, myasthenia gravis, thyroiditis) +++ T-Lymphocyte Disorders ++ T-cell depletion results in immune deficiency. Clinical manifestations depend on the subset(s) of T cells involved: — Depletion of TH1-type CD4+ T cells: Impaired delayed-type hypersensitivity can result in an increased risk of opportunistic infections (e.g., mycobacteria, listeria, brucella, fungi, or other intracellular organisms) as a result of the deficient cellular immune response to these organisms. — Depletion of TH2-type CD4+ T cells: Impaired secondary antibody response to bacteria, viruses and fungi. — Depletion of CD4+ regulatory T-cells: Can result in systemic autoimmune diseases. — Depletion of CD4+Th17 in skin and gastrointestinal tract: Can result in increased risk of infection in those sites. Graft-versus-host disease, mediated by T lymphocytes, usually secondary to allogeneic hematopoietic stem cell transplantation (see Chap. 40). Acquired immunodeficiency syndrome is a result of the lytic effect of the human immunodeficiency virus entry into CD4+ T lymphocytes. ++ For a more detailed discussion, see Thomas J. Kipps: Classification and Clinical Manifestations of Lymphocyte and Plasma Cell Disorders, Chap. 80, p. 1137 in Williams Hematology, 8th ed.