T-Cell Deficiencies - Primary Immunodeficiencies

T-CELL DEFICIENCIES

Pathophysiology

Defects in T cells lead to opportunistic infections. Most primary T-cell immunodeficiencies are genetic in origin. An increased sus-ceptibility to infection is common. Symptoms can vary consider-ably depending on the type of T-cell defect. Because the T cells play a regulatory role in immune system function, the loss of T-cell function is usually accompanied by some loss of B-cell activity.

DiGeorge syndrome, or thymic hypoplasia, is one example of a primary T-cell immunodeficiency. This rare congenital dis-ease results from the absence of several genes on chromosome 22 (Porth, 2002). The variation in symptoms is a result of differences in the amount of genetic material affected. T-cell deficiency occurs when the thymus gland fails to develop normally during embryo-genesis. DiGeorge syndrome is one of the few immunodeficiency disorders with symptoms that present almost immediately fol-lowing birth (Parslow et al., 2001).

Chronic mucocutaneous candidiasis with or without en-docrinopathy is another T-cell disorder associated with a selective defect in T-cell immunity; it is thought to be caused by an auto-somal recessive inheritance, affecting both males and females. It is considered an autoimmune disorder in which the thymus and other endocrine glands are involved in the autoimmune process. The disease causes extensive morbidity resulting from endocrine dysfunction.

Clinical Manifestations

Infants born with DiGeorge syndrome have hypoparathyroidism with resultant hypocalcemia resistant to standard therapy, con-genital heart disease, characteristic facial features, and possibly renal abnormalities. These infants, susceptible to yeast, fungal, protozoan, and viral infections, are particularly susceptible to childhood diseases (chickenpox, measles, and rubella), which are usually severe and may be fatal. Many of these infants are also born with congenital heart defects, which can result in congestive heart failure. The most frequent presenting sign in patients with DiGeorge syndrome is hypocalcemia that is resistant to standard therapy. It usually occurs within the first 24 hours of life (Parslow et al., 2001).

The initial presentation of chronic mucocutaneous candidia-sis may be either chronic candidal infection or idiopathic en-docrinopathy. Patients may survive to the second or third decade of life. Problems may include hypocalcemia and tetany secondary to hypofunction of the parathyroid glands. Hypofunction of the adrenal cortex (Addison’s disease) is the major cause of death in these patients; it may develop suddenly and without any history of previous symptoms.

Assessment and Diagnostic Findings

The status of T cells can be evaluated by peripheral blood lym-phocyte counts. Because T cells constitute 65% to 85% of pe-ripheral blood lymphocytes, lymphopenia may signify a T-cell deficit. Dermal sensitization of the patient or stimulation of the patient’s T cells in vitro may be conducted to determine if the T cells are capable of producing the expected responses. Immunoglobulin evaluation is not useful in infants because of the presence of maternally transmitted immunoglobulin (Parslow et al., 2001).

Medical Management

Patients with T-cell deficiency should receive P. carinii pro-phylaxis. General care includes management of hypocalcemia and correction of cardiac abnormalities. Hypocalcemia is con-trolled by oral calcium supplementation in conjunction with vitamin D or parathyroid hormone administration. Congenital heart disease frequently results in heart failure, and these pa-tients may require immediate surgical intervention in a tertiary pediatric center. Transplantation of the fetal thymus, postnatal thymus, and human leukocyte antigen (HLA)-matched bone marrow has been used for permanent reconstitution of T-cell immunity. IVIG therapy may be used if an antibody deficiency exists. This therapy may also be used to control recurrent in-fections. Prolonged survival has been reported following the successful transplantation of the thymus gland or spontaneous remission of immunodeficiency, which occurs in some patients (Parslow et al., 2001).