Classification and Clinical Manifestations of Lymphocyte and Plasma Cell Disorders

INTRODUCTION

SUMMARY

This chapter outlines the major categories of lymphocyte and plasma cell disorders.^* The disorders are classified into three main groups. The first is composed of diseases caused by defects intrinsic to lymphoid cells. The second is caused by disorders that result from factors extrinsic to lymphoid cells. The third is composed of disorders caused by neoplastic or preneoplastic lymphoid cells and are outlined in Chap. 90 using the World Health Organization classification 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 can provide a framework with which to proceed in evaluating patients with known or suspected lymphocyte and plasma cell disorders. This chapter introduces the framework and presents a roadmap to other chapters in this book that discuss each of the disorders in greater detail.

Acronyms and Abbreviations

GVHD, graft-versus-host disease; Ig, immunoglobulin; NK, natural killer; SCID, severe combined immune deficiency; Th, T helper; T_REG, CD4+ regulatory T cell.

CLASSIFICATION

Lymphocyte and plasma cell disorders can be classified into three major groups (Table 78–1). The first group, listed under “primary disorders,” is composed of lymphocyte disorders caused by intrinsic defects in lymphoid cells that result in functional abnormalities of marrow-derived (B) lymphocytes, thymic-derived (T) lymphocytes, combined T and B (impaired humoral and cellular immunity), or natural killer (NK) cells. These disorders primarily result from inborn errors in lymphocyte metabolism (Chaps. 73 to 77 and 80) and/or receptor–ligand expression (Chaps. 17 and 80). The second group, listed under “acquired disorders,” consists of disorders caused by factors extrinsic to lymphocytes resulting in immune dysfunction. These conditions most commonly result from infection with viruses, or other cellular pathogens (Chaps. 79, 81, and 82), but they also may be caused by bacteria, drugs or systemic disease of nonlymphoid cells. The third group of diseases is composed of preneoplastic and neoplastic lymphocyte disorders and is discussed in detail in Chap. 90.

Table 78–1. Classification of Disorders of Lymphocytes and Plasma Cells

I. Primary disorders

A. B-lymphocyte deficiency or dysfunction (Chap. 80)^1,2

1. Agammaglobulinemia

a. Acquired agammaglobulinemia³

b. Associated with plasma cell myeloma, heavy chain disease, light chain amyloid, Waldenström macroglobulinemia, or chronic lymphocytic leukemia (Chaps. 92 and 107–110)^4,5

c. Associated with celiac disease⁶

d. X-linked agammaglobulinemia^7,8

e. Autosomal recessive agammoglobilinemia⁹

f. Common variable immunodeficiency¹⁰

g. Transient hypogammaglobulinemia of infancy¹¹

h. Bloom syndrome¹²

i. Comel-Netherton syndrome¹³

2. Selective agammaglobulinemia (Chap. 80)

a. Immunoglobulin (Ig) M deficiency

1. Selective IgM deficiency¹⁴

2. Wiskott-Aldrich syndrome¹⁵

b. Selective IgG deficiency (Chap. 80)

c. Selective IgA deficiency^16,17

d. IgA and IgM deficiency¹⁸

e. IgA and IgG deficiency^19,20

1. CD40/CD40L deficiency

2. Activation-induced cytidine deaminase (AID) (uracil-DNA glycosylate [UNG], hyper-IgM₄) deficiency

3. PMS2 deficiency

3. Hyper-IgA^21,22

4. Hyper-IgD^23,24,25,26

5. Hyper-IgE syndrome (HIES; Chap. 80)²⁷

6. Hyper-IgE associated with HIV infection²⁸

7. Hyper-IgM immunodeficiency (Chap. 80)^19,20,29

8. X-linked lymphoproliferative disease^30,31,32

B. T-lymphocyte deficiency or dysfunction (Chap. 80)^33,34

1. Cartilage-hair hypoplasia (Chap. 80)^35,36

2. Lymphocyte function antigen-1 deficiency³⁷

3. Thymic aplasia (DiGeorge syndrome)^38,39

4. Thymic dysplasia (Nezelof syndrome)⁴⁰

5. Thymic hypoplasia^41,42

6. CD8 deficiency⁴³

7. CD3γ deficiency⁴⁴

8. Winged helix deficiency (Nude)⁴⁵

9. Interleukin-2 receptor α chain (CD25) deficiency⁴⁶

10. Signal transducer and activator of transcription 5b (STAT 5b) deficiency⁴⁷

11. Schimke syndrome⁴⁸

12. Janus kinase 3(JAK3) deficiency⁴⁹

13. γc Deficiency

14. Wiskott-Aldrich syndrome (Chaps. 80 and 120)^15,50

15. Zeta-associated protein of 70 kDa (ZAP-70) deficiency (Chap. 80)^51,52

16. Purine nucleoside phosphorylase deficiency (Chap. 80)

17. Interleukin-7 receptor deficiency (Chap. 80)

18. Major histocompatibility complex class I or II deficiency (Chap. 80)

19. Coronin-1A deficiency (Chap. 80)

20. IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome caused by mutations in FoxP3 that cause a deficiency of CD4+ regulatory T cells (T_REGs) (Chaps. 76 and 80)

21. APECED (autoimmune polyglandular, candidiasis, and ectodermal dystrophy) syndrome caused by mutations in the autoimmune regulator gene (AIRE) gene (Chaps. 6, 76, and 80)

22. Autoimmune lymphoproliferative syndrome (Chap. 80)

C. Combined T- and B-cell deficiency or dysfunction (Chap. 80)

1. Ataxia-telangiectasia⁵³

2. Combined immunodeficiency syndrome (Chap. 80)⁵⁴

a. Adenosine deaminase deficiency^55,56

b. Thymic alymphoplasia⁵⁷

c. CD45 deficiency⁵⁸

d. X-linked severe combined immunodeficiency syndrome⁵⁹

3. Major histocompatibility complex class II deficiency—bare lymphocyte syndrome (Chap. 80)⁶⁰

4. IgG and IgA deficiencies and impaired cellular immunity (type I dysgammaglobulinemia)⁶¹

5. Thymoma-associated immunodeficiency⁶²

6. Pyridoxine deficiency⁶³