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: primary disorders and acquired disorders. See Table 48–1. — Primary disorders result from defects intrinsic to B lymphocytes (eg, X-linked agammaglobulinemia), T lymphocytes (eg, congenital thymic aplasia), and/or natural killer cells, the latter usually coupled with a B- or T-cell deficiency (eg, interleukin-7 receptor α-chain deficiency) (see Chap. 50). — Acquired disorders result from physiologic or pathophysiologic responses to extrinsic factors, usually infectious agents (eg, Epstein-Barr virus or human immunodeficiency virus infection) (see Chaps. 51 and 52). Monoclonal (neoplastic) lymphocyte and plasma cell disorders are discussed in Part VIII and are classified in Chap. 53. Specific neoplastic disorders are discussed in Chaps. 54 to 71. Lymphocyte disorders can have clinical manifestations that are not restricted to cells of the immune system (eg, leprosy or systemic lupus erythematosus). In some cases, classification is influenced by disease manifestations: — Diseases caused by production of pathologic autoantibodies (eg, autoimmune hemolytic disease [see Chap. 22–24] and autoimmune thrombocytopenia [see Chap. 73]). — Diseases caused by excess production of lymphocyte cytokines (eg, chronic inflammatory disorders). ++Table Graphic Jump LocationTABLE 48–1CLASSIFICATION OF NONCLONAL DISORDERS OF LYMPHOCYTES AND PLASMA CELLSView Table||Download (.pdf) TABLE 48–1 CLASSIFICATION OF NONCLONAL DISORDERS OF LYMPHOCYTES AND PLASMA CELLS Primary disorders B-lymphocyte deficiency or dysfunction Agammaglobulinemia Acquired agammaglobulinemia Associated with plasma cell myeloma, heavy chain disease, light chain amyloid, Waldenström macroglobulinemia, or chronic lymphocytic leukemia Associated with celiac disease X-linked agammaglobulinemia of Bruton Autosomal recessive agammaglobulinemia Common variable immunodeficiency Transient hypogammaglobulinemia of infancy Bloom syndrome Comel-Netherton syndrome Selective agammaglobulinemia Immunoglobulin (Ig) M deficiency (1) Selective IgM deficiency (2) Wiskott-Aldrich syndrome Selective IgG deficiency IgA deficiency (1) Isolated asymptomatic (2) Steatorrheic IgA and IgM deficiency IgA and IgG deficiency (1) CD40/CD40L deficiency (2) Activation-induced cytidine deaminase (AID) (uracil-DNA glycosylate [UNG], hyper-IgM) (3) PMS2 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 CD8 deficiency CD3γ deficiency Winged helix deficiency (Nude) Interleukin-2 receptor α chain (CD25) deficiency Signal transducer and activator of transcription 5b (STAT 5b) deficiency Schimke syndrome Janus kinase 3(JAK3) deficiency γc Deficiency Wiskott-Aldrich syndrome Zeta-associated protein of 70kDa (ZAP-70) deficiency Purine nucleoside phosphorylase deficiency Interleukin-7 receptor deficiency Major histocompatibility complex class I or II deficiency Coronin-1A deficiency IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome caused by mutations in FoxP3 that cause a deficiency of CD4+ regulatory T cells (Tregs) APECED (autoimmune polyglandular, candidiasis, and ectodermal dystrophy) syndrome caused by mutations in the autoimmune regulator gene (AIRE) gene Autoimmune lymphoproliferative syndrome Combined T- and B-cell deficiency or dysfunction Ataxia-telangiectasia Combined immunodeficiency syndrome Adenosine deaminase deficiency Thymic alymphoplasia CD45 deficiency X-linked severe combined immunodeficiency syndrome Major histocompatibility complex class II deficiency—bare lymphocyte syndrome IgG and IgA deficiency and impaired cellular immunity (type I dysgammaglobulinemia) Thymoma-association immunodeficiency Pyridoxine deficiency Reticular agenesis (congenital aleukocytosis) Omenn syndrome Warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome resulting from mutation in the CXCR4 gene Natural killer cells: chronic natural killer cell lymphocytosis Acquired disorders Acquired immunodeficiency syndrome (AIDS) Reactive lymphocytosis or plasmacytosis Bordetella pertussis lymphocytosis Cytomegalovirus mononucleosis Drug-induced lymphocytosis Stress-induced lymphocytosis Persistent polyclonal B-cell lymphocytosis Postsplenectomy lymphocytosis Epstein-Barr virus mononucleosis Inflammatory (secondary) plasmacytosis of marrow Large granular lymphocytosis Other viral mononucleosis Polyclonal lymphocytosis Serum sickness T-cell lymphocytosis associated with thymoma Toxoplasma gondii mononucleosis Trypanosoma cruzi Viral infectious lymphocytosis Cat-scratch and other chronic bacterial infection T-lymphocyte dysfunction or depletion associated with systemic disease B-cell chronic lymphocytic leukemia Hodgkin lymphoma Leprosy Lupus erythematosus Sjögren syndrome Sarcoidosis Source: Williams Hematology, 9th ed, Chap. 78, Table 78–1. + CLINICAL MANIFESTATIONS Download Section PDF Listen +++ +++ B-Lymphocyte Disorders ++ Infection with any class of microorganism (eg, bacteria, viruses, fungi) occurs because of immunoglobulin deficiency and impaired opsonization and clearance of pathogen. Tissue or organ abnormality is a result of pathogenic autoantibodies (eg, immune hemolytic anemia, immune thrombocytopenia, myasthenia gravis, thyroiditis). Primary defect in the B-cell clone or expansion of a clone in response to chronic antigen stimulations can result in excess production of immunoglobulin that in turn produces a monoclonal gammopathy (Chap. 67). +++ 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 lead to an increased risk of opportunistic infections (eg, 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. This is an impaired secondary antibody response to bacteria, viruses, and fungi. — Depletion of CD4+ regulatory T-cells. Systemic autoimmune diseases can occur as a result. — Depletion of CD4+ Th17 in skin and gastrointestinal tract. This can lead to increased risk of infection in those sites. Graft-versus-host disease, mediated by T lymphocytes, is usually secondary to allogeneic hematopoietic cell transplantation (see Chap. 39). ++ For a more detailed discussion, see Yvonne A. Efebera and Michael A. Caligiuri: Classification and Clinical Manifestations of Lymphocyte and Plasma Cell Disorders, Chap. 78 in Williams Hematology, 9th ed.