Page 500 - Clinical Immunology_ Principles and Practice ( PDFDrive )

480 PARt fouR Immunological Deficiencies

IgAD is associated with an increased risk for the development TABLE 34.3 other Conditions Associated
of malignant epithelial tumors, such as gastric and colonic With Humoral Immunodeficiency
adenocarcinoma, Hodgkin disease, and acute lymphoblastic
leukemia. Patients with chronic GI infections may demonstrate Genetic Disorders
a nodular lymphoid hyperplasia of the small intestine that can Monogenic diseases Ataxia–telangiectasia
lead to intestinal obstruction. Histological evaluation reveals Autosomal forms of severe combined
immunodeficiency (SCID)
active B-lymphocyte proliferation in the germinal centers of the Transcobalamin II deficiency and
Peyer patches. These “constipated” lymph nodes have been hypogammaglobulinemia
mistaken for lymphoma. In others, the simultaneous presence Wiskott-Aldrich syndrome
of IgAD and malignancy may simply reflect the high prevalence X-linked lymphoproliferative disorder (Epstein-
of IgAD in the Caucasian population. Barr virus [EBV] associated)
X-linked SCID
Origin and Pathogenesis Chromosomal Chromosome 18q- syndrome
anomalies Monosomy 22
IgAD, selective IgG subclass deficiencies, and CVID are diseases Trisomy 8
that are defined by a quantitative phenotype, a paucity of serum Trisomy 21
Igs of a given isotype in spite of the presence in the blood of B
lymphocytes bearing the missing isotypes. By definition, the Systemic Disorders
fundamental defect involves the failure of B lymphocytes bearing Malignancy Chronic lymphocytic leukemia
a given isotype to differentiate into plasma cells. These diseases Immunodeficiency with thymoma
appear to represent a common endpoint for multiple pathogenic T-cell lymphoma
processes. All three phenotypes may be acquired and many of Metabolic or physical Immunodeficiency caused by hypercatabolism of
immunoglobulin
loss
the recognized precipitating causes, such as phenytoin, are the Immunodeficiency caused by excessive loss of
same (Table 34.3). immunoglobulins and lymphocytes
IgA deficiency is associated with MHC haplotypes (6p21.3)
that are more common in European populations than in the Environmental Exposures
peoples of Sub-Saharan African and East Asia. In the United Drug-induced Antimalarial agents
States, the prevalence of IgAD among African Americans is Captopril
one-twentieth of that observed among Americans of European Carbamazepine
descent, and in Japan, the incidence is approximately 1 in 18 500. Glucocorticoids
Fenclofenac
IgA deficiency has also been observed in family members of Gold salts
patients with CVID with altered function of the transmembrane Imatinib
activator and CAML interactor (TACI, 17p11.2), which is a Levetiracetam
receptor for B cell–activating factor (BAFF). Penicillamine
Phenytoin
Treatment and Prognosis Sulfasalazine
Zonisamide
Most individuals with IgAD suffer respiratory infections no more Infectious diseases Congenital rubella
frequently than the average individual and thus require no special Congenital infection with cytomegalovirus (CMV)
treatment. All individuals with IgA deficiency should be warned Congenital infection with Toxoplasma gondii
of the risk of serious transfusion reactions caused by antibodies EBV
to IgA. Wearing a medical alert bracelet is recommended. Should Human immunodeficiency virus (HIV)
transfusion be necessary, the ideal donors are other individuals
with IgAD. Washed erythrocytes are safer than whole blood.
Patients with selective IgA deficiency who suffer from clinically
significant, recurrent upper respiratory infections often respond impaired. In the presence of infection, abortive differentiation
to prophylactic antibiotics with potency against encapsulated can lead to massive B-lymphocyte hyperplasia, splenomegaly,
bacteria. Treatment of allergy in those patients with a compensa- and intestinal lymphoid hyperplasia.
tory increase in IgE is helpful. Patients who present with combined With an estimated prevalence of 1 in 25 000, CVID is the
IgA and IgG subclass deficiencies and have a poor pneumococcal most prevalent human primary immunodeficiency requiring
26
antibody response may require IG replacement therapy. medical attention. Both sexes are equally affected. As with IgAD,
the prevalence among African Americans is one-twentieth that
COMMON VARIABLE IMMUNODEFICIENCY AND of Americans of European descent. Some patients present during
CVID-LIKE DISORDERS childhood, but most are diagnosed after the third decade of life.
The typical patient reports a normal pattern of recurrent otitis
Diagnosis media as an infant and toddler that resolved in childhood. During
The diagnostic category of CVID includes a heterogeneous group adolescence, respiratory infections appear and steadily increase
of patients older than age 4 years and exhibit deficient production in frequency and duration. Recurrent pneumonia as a young or
of more than one major antibody class and whose antibody middle-aged adult is often the precipitating complaint that brings
response to vaccination is significantly depressed or absent. These the patient to the attention of the clinical immunologist. Although
patients tend to have normal numbers of clonally diverse B CVID appears to be an acquired disorder, family studies have
lymphocytes in their blood. These B cells can recognize antigens clearly documented that susceptibility for the disease can be
and respond with proliferation, but their ability to develop into inherited and the manifestations of the disorder may change
memory B cells or mature plasma cells appears quantitatively with time. Transitions within the spectrum of normal serum Ig