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CHAPTER 78 be difficult to distinguish clinically because lymphocyte disorders can
Some categories of lymphocyte and plasma cell disorders may
CLASSIFICATION AND have many clinical manifestations that are not restricted to cells of the
immune system and disparate disorders can have similar clinical mani-
CLINICAL MANIFESTATIONS festations, with any one disorder associated with a diverse array of clin-
ical pathologies.
In some cases, the classification of lymphocyte disorders is influ-
OF LYMPHOCYTE AND enced by the manifestations of the disease. For example, autoimmune
hemolytic disease (Chap. 54) and autoimmune thrombocytopenia
PLASMA CELL DISORDERS (Chap. 117) are caused by inappropriate secretion of autoantibodies by
B lymphocytes. The blood cell that is coated with autoantibody presum-
ably is normal, yet we classify the disease that can result from hemolytic
autoantibodies as an acquired hemolytic anemia because that aspect of
Yvonne A. Efebera and Michael A. Caligiuri* the disease is more visible and better understood than is the inappropri-
ate synthesis of antierythrocyte antibody by the disturbed lymphocyte
population(s). These disorders are not considered here.
Many diseases, especially infection (e.g., tuberculous adenitis),
SUMMARY inflammatory states (e.g., rheumatoid arthritis), autoimmune disease
(e.g., systemic lupus erythematosus), and metastatic carcinoma can
This chapter outlines the major categories of lymphocyte and plasma cell dis- involve lymph nodes or the spleen as a secondary alteration. These dis-
orders. The disorders are classified into three main groups. The first is com- orders also may be associated with abnormal production of antibodies,
posed of diseases caused by defects intrinsic to lymphoid cells. The second is such as those resulting in the lupus anticoagulant (Chap. 131). These
caused by disorders that result from factors extrinsic to lymphoid cells. The disorders also are not considered here because the primary disease is
third is composed of disorders caused by neoplastic or preneoplastic lymphoid not generally considered a lymphocyte disorder.
cells and are outlined in Chap. 90 using the World Health Organization classifi-
cation of tumors of lymphoid tissues. The clinical manifestations of diseases in
any one of the three groups may be difficult to distinguish, but this grouping CLINICAL MANIFESTATIONS
can provide a framework with which to proceed in evaluating patients with B LYMPHOCYTE DISORDERS
known or suspected lymphocyte and plasma cell disorders. This chapter intro-
duces the framework and presents a roadmap to other chapters in this book Immunoglobulin Deficiency
that discuss each of the disorders in greater detail. The clinical manifestations of B-lymphocyte disorders include the con-
sequences of B-lymphocyte deficiency, dysfunction, or malignant trans-
formation. The manifestations may consist of a specific deficiency of
CLASSIFICATION one of the immunoglobulin (Ig) isotypes or of several or all Ig mole-
cules (panhypogammaglobulinemia; see Chap. 75). Inability to synthe-
Lymphocyte and plasma cell disorders can be classified into three major size or secrete antibodies impairs the clearance of pathogens because of
groups (Table 78–1). The first group, listed under “primary disorders,” the inability to opsonize microorganisms for phagocytosis, resulting in
is composed of lymphocyte disorders caused by intrinsic defects in lym- immune dysregulation and dysfunction (Chap. 80).
phoid cells that result in functional abnormalities of marrow-derived
(B) lymphocytes, thymic-derived (T) lymphocytes, combined T and Abnormal Immunoglobulin Production
B (impaired humoral and cellular immunity), or natural killer (NK) Primary defect in the B-cell clone or expansion of a clone in response
cells. These disorders primarily result from inborn errors in lymphocyte to chronic antigen stimulation can result in excess production of Ig that
metabolism (Chaps. 73 to 77 and 80) and/or receptor–ligand expression in turn produces a monoclonal gammopathy (Chap. 106). Monoclonal
(Chaps. 17 and 80). The second group, listed under “acquired disorders,” gammopathy can result in B-cell neoplastic disease, such as plasma cell
consists of disorders caused by factors extrinsic to lymphocytes result- myeloma (Chap. 107), Waldenström macroglobulinemia (Chap. 109) or
ing in immune dysfunction. These conditions most commonly result chronic lymphocytic leukemia (Chap. 92). Production of abnormal Ig
from infection with viruses, or other cellular pathogens (Chaps. 79, 81, molecules or Ig fragments can also be seen in association with chronic
and 82), but they also may be caused by bacteria, drugs or systemic infection, leading to development of Ig heavy-chain disease (Chap. 110).
disease of nonlymphoid cells. The third group of diseases is composed Deposition of Ig or Ig fragments can contribute to primary amyloid for-
of preneoplastic and neoplastic lymphocyte disorders and is discussed mation (Chap. 108). Reactivity of the Ig with self-antigen(s), such as
in detail in Chap. 90. those found on the red cell membrane (Chap. 54), can result in systemic
autoimmune disease.

T LYMPHOCYTE DISORDERS
Acronyms and Abbreviations: GVHD, graft-versus-host disease; Ig, immuno- Impaired Immunoregulation
globulin; NK, natural killer; SCID, severe combined immune deficiency; Th, T helper; The clinical manifestations of deficiencies or excesses of T-lympho-
T , CD4+ regulatory T cell.
REG cytes depend on the subset of T-lymphocytes involved. Delayed hyper-
sensitivity normally is mediated by CD4+ helper T cells (Th cells) and,
more specifically, Th1-type cells (Chap. 76). A deficit or functional
∗ This chapter was prepared by Thomas J. Kipps in the 8th edition and much of disturbance in these T-cells can impair the cellular immune response
the text has been retained. to mycobacteria, Listeria, Brucella, fungi, or other intracellular

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