eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology
B-Cell and T-Cell Combined Disorders
Updated: Nov 12, 2009
Introduction
Background
The immune system's lymphocyte component is divided into B cells and T cells. Traditionally, B cells have been believed to be the lymphocytes responsible for antibody production via maturation into plasma cells (ie, humoral immunity), and T cells have been believed to be the lymphocytes responsible for killing other cells or organisms (ie, cellular immunity). Currently, certain T lymphocytes (ie, T-helper cells) are known to be responsible for helping immature B cells develop into mature B cells. Other T lymphocytes (ie, T-suppressor/cytotoxic cells) possess the killing function and also inhibit B-cell development. Therefore, any T-cell disorder theoretically has the potential to cause defective B-cell function.
Pathophysiology
Because a major loss or dysfunction of T cells can cause secondary B-cell deficiency, numerous disorders have clinical manifestations of combined B-cell and T-cell deficiency, although the only pathology is in the T cell. In converse, some diseases appear to primarily involve the T cells and do not appear to affect antibody production. Those diseases are discussed in T-Cell Disorders.
Development of mature functioning B and T cells involves a complex series of steps, each of which may be defective, resulting in B-cell and T-cell deficiency. When T-cell deficiency is especially severe or involves the T-helper cell function, the deficiency causes an antibody deficiency. The most severe manifestations occur within the first 2 years of life as various types of severe combined immunodeficiency (SCID). See Omenn Syndrome and Purine Nucleoside Phosphorylase Deficiency for a discussion of other forms of SCID.
Omenn syndrome is the result of mutations in the genes coding for recombinases (recombination activating genes). RAG1 and RAG2 cause a defect in the variable diversity joining (VDJ) rearrangement needed for mature T and B cells to develop. Deficiency of purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) elevates intracellular levels of deoxyguanosine and deoxyadenosine, respectively. Deoxyguanosine and deoxyadenosine are more toxic in lymphocytes than in other cell types. Deficiency of the expression of major histocompatibility complex (MHC) class I and II cellular proteins also commonly manifests in early infancy with classic symptoms of SCID. Symptoms in affected patients indicate the crucial involvement of MHC proteins in the immune recognition of self and nonself.
In other B-cell and T-cell disorders, additional anomalies may predominate, and clinical manifestations suggestive of immunodeficiency may occur late in life. Recognize that patients with short-limbed skeletal dysplasia with cartilage-hair hypoplasia can also have either a T-cell or combined defect. See Cartilage-Hair Hypoplasia.
Male patients with thrombocytopenia and eczema may have Wiskott-Aldrich syndrome with defective T-cell function and resultant recurrent infections. They have poor antibody responses to polysaccharide antigens but elevated levels of serum immunoglobulin A (IgA) and immunoglobulin E (IgE) with low levels of immunoglobulin M (IgM). See Wiskott-Aldrich Syndrome.
Two autosomal recessive syndromes indicate some interaction of the immune system with neurologic function. Ataxia-telangiectasia (AT) is a rare, autosomal recessive, neurodegenerative disorder in which the diagnosis is obvious when both ataxia and telangiectasia are present. Multisystemic manifestations of AT include motor impairments secondary to a neurodegenerative process, oculocutaneous telangiectasia, sinopulmonary infections, hypersensitivity to ionizing radiation, and a combined immunodeficiency that can be quite variable. This is discussed in additional detail in this article.
Nijmegen breakage syndrome (NBS) is also an autosomal recessive chromosomal instability syndrome. NBS is characterized by microcephaly with growth retardation, normal or impaired intelligence, birdlike facies, increased susceptibility to infection, humoral and cellular immunodeficiency, and high risk for lymphatic tumor development. Nearly all patients with NBS are homozygous for the same founder mutation, ie, deletion of 5 bp (657del5) in the NBS1 gene, which encodes the protein nibrin. Because most patients with NBS are of Slavonic origin, this frameshift mutation came to be called the Slavonic mutation.
These 2 syndromes, AT and NBS, are part of a family of mutations involving proteins involved in DNA repair. Ataxialike disorder (ATLD) syndrome involves a mutation in meiotic recombination 11 homolog (MRE11). These 3 syndromes are associated with decrease circulating levels of T cells (but circulating levels of B cells are normal) and often decreased levels of IgA, IgE, and IgG subclasses. Artemis deficiency (with mutations in the Artemis protein resulting in defective VDJ recombination) decreases both T cells and B cells and can be considered part of a subset of SCIDs. DNA ligase IV deficiency likewise results in circulating T cells and B cells and serum immunoglobulins. Finally, Bloom syndrome results from a mutation in the helicase enzyme called BLM RecQ. All of these defects in DNA repair are characterized by an increased risk of malignancy and radiation sensitivity.
Two syndromes indicate close interaction between the immune and endocrine systems: chronic mucocutaneous candidiasis (CMC) and immune dysregulation with polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.1CMC is a complex disorder in which patients have persistent or recurrent infections of the skin, nails, and mucous membranes by Candida species. It can be broadly classified into familial (inherited) or nonfamilial (noninherited) forms. Familial forms are inherited as autosomal dominant or autosomal recessive and are associated with or without varying degrees of autoimmune endocrinopathy. Two other familial subtypes include an autosomal dominant form with nail candidiasis and intercellular adhesion molecule-1 (ICAM-1) deficiency and an autosomal recessive form with hyperimmunoglobulin E.
CMC is included as part of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) disorder, which is also known as autoimmune polyglandular syndrome type I (APS I). This disease has been mapped to chromosome 21q22.3 and the gene identified as the autoimmune regulator (AIRE) gene. It appears to be involved in DNA binding. At least 60 different disease-causing mutations in AIRE have been discovered and the role in various manifestations of CMC and APECED/APS I are under investigation.
IPEX syndrome is associated with mutations in the FOXP3 gene at Xp11.23. Affected males have diarrhea (enteropathy) and autoimmune phenomena primarily involving the endocrine system, such as diabetes or thyroid disease. Other autoimmune processes may include hemolytic anemia and collagen-vascular disease. The typical triad consists of enteropathy, dermatitis, and endocrine abnormalities. Most individuals with this condition do not live beyond age 3 years.
Frequency
United States
Stiehm estimated that combined cellular and antibody deficiencies account for approximately 20% of primary immunodeficiencies.2 AT is a rare disease with an estimated prevalence of less than 1 case per 100,000 population; the incidence of CMC is similar at 1 case per 103,000 population. Some report an increased frequency of approximately 1 case of AT per 40,000 births in the United States.
International
In Brazil, combined immunodeficiency defects accounted for 16 (9.6%) of 166 primary immunodeficiencies in children examined over 15 years. In Spain's Registry for Primary Immunodeficiency Diseases, 14.7% were T-cell and combined deficiencies, similar to the 20.2% reported in the European registry report. In a survey of 201 Swedish patients from 1974-1979, 20.8% had combined T-cell and B-cell disorders.
The birth frequency of AT in the United Kingdom is approximately 1 case per 300,000 population. In the Slavonic population, the prevalence of AT appears higher (1:40,000-100,000) than the prevalence of NBS (1:60,000-120,000). CMC with APECED is inherited as an autosomal recessive trait and appears to be prevalent in genetically isolated populations of the Finns, the Iranian Jews, and the Sardinians (with prevalences of 1:25,000, 1:9000, and 1:14,500, respectively). Indeed, the Finnish series of patients is the largest internationally.3
Mortality/Morbidity
Similar to patients with B-cell deficiency, a major cause of mortality and morbidity is recurrent upper and lower respiratory infections because patients cannot mount an adequate immune reaction. Patients' increased susceptibility to development of malignancy also indicates the importance of T cells in immune surveillance and the role of cellular immunity in the protection against tumor cells. Abnormal immune systems in patients can produce autoimmune reactions in which an inappropriate exaggerated reaction can occur toward self-antigens.
Race
Although combined B-cell and T-cell disorders are rare, they are described in all races.
Sex
No differences have been reported based on sex except in IPEX syndrome.
Age
The disorders almost always occur in young infants, and the syndrome can often be recognized on the basis of its nonimmunologic manifestations.
Clinical
History
Clinical manifestations of many combined B-cell and T-cell deficiencies derive from associated organ involvement, thus eliciting variable onsets for the different symptoms. Neurologic and cutaneous symptoms predominate in ataxia-telangiectasia (AT) and Nijmegen breakage syndrome (NBS). Autoimmune endocrinopathies and cutaneous manifestations are seen in patients with chronic mucocutaneous candidiasis (CMC) and immune dysregulation with polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. In other combined B-cell and T-cell deficiencies, the presence of unusual organisms in certain infections, the chronic nature of infectious processes, and autoimmune phenomena may indicate the presence of an underlying immunodeficiency.
- AT is an obvious diagnosis when both ataxia and telangiectasia are present. A diagnosis of AT can also be made upon onset of ataxia and before telangiectasia appears, if confirmed by laboratory test results. In most patients, a misdiagnosis of cerebral palsy is usually made because ataxia most often occurs during infancy. Telangiectasia usually does not appear until patients are aged 5 years.
- In a review of 48 patients with AT, mean age of ataxia onset was 15 months; mean age of telangiectasia onset was 72 months.4 This study by confirmed that a misdiagnosis of cerebral palsy was made in most patients (29 of 48). To alleviate this problem, the study recommends routine serum alpha-fetoprotein (AFP) testing for all children with persistent ataxia.
- Ataxia is initially cerebellar, with associated posture and gait problems. Speech may become slurred. Movement disorders also occur and may be choreoathetoid or ticlike. Oculomotor apraxia is usually present, and, less often, a dysconjugate gaze is noted. Muscle weakness may appear late in the course, with subsequent muscle atrophy. Mental function can be affected.
- AT has increased alpha fetoprotein levels, whereas NBS has microcephaly and mental retardation.
- Telangiectasia usually occurs on the bulbar conjunctivae in patients younger than 5-6 years and becomes more prominent in other areas, especially the pinna. Other cutaneous manifestations include progressive cutaneous atrophy, areas of hypopigmentation or hyperpigmentation, hypertrichosis, atopic dermatitis, and cutaneous malignancies.
Telangiectasia.
Telangiectasia of conjunctivae.
- Bloom syndrome may also have telangiectasias, especially sun-exposed areas. However, patients have short stature and birdlike facies.
- All patients have a deficiency of cell-mediated immunity. However, deficiency in humoral immunity is more variable. Therefore, the resulting predisposition to infection can vary. Recurrent sinopulmonary infections may be a complaint before ataxia or telangiectasia develops. An increase in lower respiratory tract infections is observed with age with subsequent chronic lung disease. Impaired oropharyngeal swallowing mechanisms may contribute with chronic aspiration. Infections can be caused by viral and bacterial pathogens, although typically not by opportunistic agents.
- In a review of 100 patients with AT, recurrent upper and lower tract infections were common, including otitis media in 46%, sinusitis in 27%, bronchitis in 19%, and pneumonia in 15%. Systemic bacterial and severe viral or opportunistic infections were uncommon.
- Although endocrine abnormalities are uncommon, they may include failure to develop secondary sex characteristics. Stiehm states that no offspring of AT homozygotes are known.2 Patients may also have growth failure.
- Patients with CMC have persistent or recurrent candidal infections of the skin, nails, and mucous membranes. The extent and location of infections, genetic factors, and associated autoimmune disorders delineate 6 clinical syndromes.
- Candidiasis is almost always observed in patients with CMC. Infants with CMC type 3 usually present with persistent diaper rash or other localized lesions involving the extremities. Extreme hyperkeratosis may occur. Persistent or recurrent thrush is also common. Consider CMC in patients when chronic oral candidiasis (CMC type 1) continues after cessation of antibiotics or inhaled corticosteroid therapy and when T-cell deficiency has been excluded. Esophageal or tracheal candidiasis is uncommon and may simply represent colonization of mucous membranes after a course of systemic antibiotic therapy.
A 5-year-old boy with thrush.
- More extensive cutaneous infections with skin, nail, and mucous membrane involvement may develop in late childhood or during adolescence (CMC type 4). These patients apparently are less likely to develop endocrinopathies.
- According to Stiehm, "It is important to appreciate that the endocrinopathies may develop any time from childhood through adulthood and that patients may have sequential loss of functions of various endocrine organs..."2 According to one study, the most commonly affected organs are the parathyroid glands (54 of 68 patients), adrenal glands (49 of 68 patients), and thyroid gland (2 of 68 patients). Gonadal failure commonly causes infertility. Insulin-dependent diabetes occurs in approximately 10% of patients. Overall, CMC is associated with autoimmune endocrinopathies in about 40% of patients.
- An association of CMC with thymomas (CMC type 5) has been described, usually in adult or middle-aged patients. These patients may also have other autoimmune disorders, such as myasthenia gravis, aplastic anemia, and hypogammaglobulinemia.
- An association of chronic keratitis with CMC has been noted and appears to be an autosomal dominant trait.
- Patients with CMC are susceptible to frequent infections by viruses and bacteria in the skin and in the upper and lower respiratory tracts.
- Other autoimmune disorders are common and include various autoimmune hematologic disorders (eg, red blood cell [RBC], white blood cell [WBC], platelets), chronic active hepatitis, and juvenile rheumatoid arthritis for CMC.
- The combination of dermatitis and thrombocytopenia (as an autoimmune process) in males may confuse IPEX with patients with Wiskott-Aldrich syndrome. Indeed, IPEX was originally thought to be a Wiskott-Aldrich syndrome variant because the gene that encodes WASP also lies in the same region as FOXP3 gene. The dermatitis in IPEX is also eczematous in nature.
- Enteropathy with failure to thrive is almost always present in IPEX. It usually presents with watery diarrhea and villous atrophy is commonly found on intestinal biopsy.
- Endocrinopathy is commonly present but may not appear initially. The most common endocrine dysfunction is early onset insulin-dependent diabetes mellitus. Thyroid disease (either hypothyroidism or hyperthyroidism) is also common.
- Examples of autoimmune phenomena include immune hemolytic anemia, immune thrombocytopenia, autoimmune neutropenia, lymphadenopathy, splenomegaly, tubular nephropathy, or alopecia.
- Patients with IPEX usually present in early infancy and may die within the first 2 years of life due to either metabolic derangements or sepsis. The most common pathogens were Staphylococcus, cytomegalovirus (CMV), and Candida.
- Neoplastic diseases other than thymomas can occur, which emphasizes the importance of T cells in immune surveillance. However, a greater incidence of malignancy is observed in AT, especially lymphoid tumors, which has been attributed to their increased sensitivity to radiation. Occasionally, leukemia has been a presenting finding of AT. On the other hand, CMC with squamous cell carcinoma of the oral cavity or esophagus has also been described.5
Physical
Depending on the specific combined immunodeficiency syndromes, physical examination may yield varying signs, as follows:
- In patients with AT, gait abnormalities occur at a median age of 15 months. Deterioration of the newly acquired developmental milestone of walking signals a problem.
- All patients manifest progressive cerebellar ataxia. However, the classic form has onset in infancy, and steady progression to milder forms in which the progression may be slower or the onset may be later have been noted. Other neurologic signs include dystonia and oculomotor apraxia. Drooling, strabismus, and a masklike facies may be seen. In addition to cerebellar signs, extrapyramidal and posterior column signs may be present. Reflexes are decreased, and muscle weakness may be present. Sensory involvement is uncommon.
- Telangiectasia is commonly observed on the bulbar conjunctivae and may occur in children aged 1-6 years. Other areas, such as the lateral aspect of the nose, the ears, the antecubital and popliteal areas, and the dorsa of the hands and feet, may be affected later.
- In CMC, almost all patients have skin or nail findings.6 Mucous membranes in the oral cavity may be covered with a patchy pseudomembrane composed of mycelial Candida albicans (ie, thrush). Infants may have a persistent diaper rash with fungal infection. In more extensive forms, nails and extremities may develop severe hyperkeratosis with nail deformities.
- In IPEX, the typical rash is eczematoid.
Causes
- The gene responsible for AT, designated ATM (ie, AT, mutated), encodes for a protein that belongs to a family of phosphatidylinositol 3-kinase (PI3-K)–related kinases (PIKK). Members of this family are involved in mitogenic signal transduction, intracellular protein transport, and control of the cell cycle. In biologic terms, cells have an extreme sensitivity to radiation and an increased predisposition to become cancerous.
- ATM is located on the long arm of chromosome 11 at subband q22.3. ATM is a large gene, with over 300 mutations described in 66 exons and no common, predominant mutation.
- In contrast, the NBS1 gene involved in NBS is located on chromosomal band 8q21. Seven mutations are reported worldwide, with a high predominance of the founder mutation 567del5 in the Slavonic population.
- Most patients with the classic AT phenotype are homozygous or compound heterozygous for ATM mutations that result in a truncated or unstable protein with total loss of ATM function. Some patients have mild forms of the disease, termed AT variants, and are either homozygous for mild mutations or compound heterozygotes for mild mutations. These mutations are leaky splice or missense mutations. Preservation of neurologic function is correlated with the degree of ATM protein kinase activity. About 10% of normal ATM kinase activity is apparently adequate to moderate the phenotype but not to prevent it.
- The additional recognition of many ATM substrates involved in the recognition and repair of DNA double-strand breaks may also allow for the heterologous symptoms among patients with AT, some of whom may not have symptoms until adulthood.
- Mutations in the ATM gene are probably not a common cause for cerebellar ataxia other than AT.
- With the aid of molecular testing, AT can be distinguished from other autosomal recessive cerebellar ataxias, such as Friedrich ataxia, Mre11 deficiency (AT-like disease), and the oculomotor apraxias 1 (aprataxin deficiency) and 2 (senataxin deficiency). In addition, NBS1 deficiency defines NBS syndrome, and helicase gene defect defines Bloom syndrome.
- Heterogeneous manifestations of CMC may indicate numerous causes and a heterogeneous pattern of inheritance.
- Immunological studies indicate that dendritic maturation may be impaired in both CMC and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Subsequent altered regulation of pattern recognition receptors may be responsible for the disease manifestions.7
- Other studies show that these patients have an inability to clear Candida. This may be due to a defect in the immune response of interleukin (IL)-17-producing T cells.8
- CMC is included as part of the APECED disorder, which is also known as autoimmune polyglandular syndrome type I (APS I). This disease has been mapped to chromosome 21q22.3, and the gene is identified as the autoimmune regulator (AIRE) gene. It appears to be involved in DNA binding. At least 60 different disease-causing mutations in AIRE have been discovered, and the role in various manifestations of CMC and APECED/APS I are under investigation. AIRE may be involved in thymocyte negative selection, which may partially account for autoimmunity.
- CMC can be broadly classified into familial (inherited) or nonfamilial (noninherited) forms. Familial forms are inherited as autosomal dominant or autosomal recessive and are associated with or without varying degrees of autoimmune endocrinopathy. Therefore, determining whether the AIRE gene markers (and autoantibodies) segregate with disease in a family in whom the diagnosis of CMC is possible is important.
- Two other familial subtypes include an autosomal dominant form with nail candidiasis and intercellular adhesion molecule-1 (ICAM-1) deficiency and an autosomal recessive form with hyperimmunoglobulinemia E. Chronic localized CMC has no apparent genetic component.
More on B-Cell and T-Cell Combined Disorders |
 Overview: B-Cell and T-Cell Combined Disorders |
| Differential Diagnoses & Workup: B-Cell and T-Cell Combined Disorders |
| Treatment & Medication: B-Cell and T-Cell Combined Disorders |
| Follow-up: B-Cell and T-Cell Combined Disorders |
| Multimedia: B-Cell and T-Cell Combined Disorders |
| References |
| Next Page » |
References
Moraes-Vasconcelos D, Costa-Carvalho BT, Torgerson TR, Ochs HD. Primary immune deficiency disorders presenting as autoimmune diseases: IPEX and APECED. J Clin Immunol. May 2008;28 Suppl 1:S11-9. [Medline].
Stiehm ER. Immunologic Disorders in Infants and Children. 4th ed. WB Saunders Co; 1996.
Perheentupa J. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab. Aug 2006;91(8):2843-50. [Medline].
Cabana MD, Crawford TO, Winkelstein JA, Christensen JR, Lederman HM. Consequences of the delayed diagnosis of ataxia-telangiectasia. Pediatrics. Jul 1998;102(1 Pt 1):98-100. [Medline].
Rosa DD, Pasqualotto AC, Denning DW. Chronic mucocutaneous candidiasis and oesophageal cancer. Med Mycol. Feb 2008;46(1):85-91. [Medline].
LeBoeuf N, Garg A, Worobec S. The autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. Pediatr Dermatol. Sep-Oct 2007;24(5):529-33. [Medline].
Hong M, Ryan KR, Arkwright PD, et al. Pattern recognition receptor expression is not impaired in patients with chronic mucocutanous candidiasis with or without autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. Clin Exp Immunol. Apr 2009;156(1):40-51. [Medline].
Eyerich K, Foerster S, Rombold S, et al. Patients with chronic mucocutaneous candidiasis exhibit reduced production of Th17-associated cytokines IL-17 and IL-22. J Invest Dermatol. Nov 2008;128(11):2640-5. [Medline].
Stray-Pedersen A, Aaberge IS, Fruh A, Abrahamsen TG. Pneumococcal conjugate vaccine followed by pneumococcal polysaccharide vaccine; immunogenicity in patients with ataxia-telangiectasia. Clin Exp Immunol. Jun 2005;140(3):507-16. [Medline].
Pashankar F, Singhal V, Akabogu I, Gatti RA, Goldman FD. Intact T cell responses in ataxia telangiectasia. Clin Immunol. Aug 2006;120(2):156-62. [Medline].
Meloni A, Furcas M, Cetani F, et al. Autoantibodies against type I interferons as an additional diagnostic criterion for autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab. Nov 2008;93(11):4389-97. [Medline].
Meager A, Visvalingam K, Peterson P, et al. Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1. PLoS Med. Jul 2006;3(7):e289. [Medline].
Kalfa VC, Roberts RL, Stiehm ER. The syndrome of chronic mucocutaneous candidiasis with selective antibody deficiency. Ann Allergy Asthma Immunol. Feb 2003;90(2):259-64. [Medline].
Stiehm ER, Casillas AM, Finkelstein JZ, et al. Slow subcutaneous human intravenous immunoglobulin in the treatment of antibody immunodeficiency: use of an old method with a new product. J Allergy Clin Immunol. Jun 1998;101(6 Pt 1):848-9. [Medline].
Renwick A, Thompson D, Seal S, et al. ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet. Aug 2006;38(8):873-5. [Medline].
Buoni S, Zannolli R, Sorrentino L, Fois A. Betamethasone and improvement of neurological symptoms in ataxia-telangiectasia. Arch Neurol. Oct 2006;63(10):1479-82. [Medline].
Crawford TO, Skolasky RL, Fernandez R, Rosquist KJ, Lederman HM. Survival probability in ataxia telangiectasia. Arch Dis Child. Jul 2006;91(7):610-1. [Medline].
Baumgart KW, Britton WJ, Kemp A, French M, Roberton D. The spectrum of primary immunodeficiency disorders in Australia. J Allergy Clin Immunol. Sep 1997;100(3):415-23. [Medline].
Claret Teruel G, Giner Munoz MT, Plaza Martin AM, et al. Variability of immunodeficiency associated with ataxia telangiectasia and clinical evolution in 12 affected patients. Pediatr Allergy Immunol. Nov 2005;16(7):615-8. [Medline].
Hughes WT. Prevention of infections in patients with T cell defects. Clin Infect Dis. Nov 1993;17 Suppl 2:S368-71. [Medline].
Lacy CF, Armstrong LL, Goldman MP, Lance LL, eds. Drug Information Handbook 2000-2001. Cleveland, Ohio: Lexi-Comp Inc; 2000.
Mila J, Matamoros N, Pons de Ves J, Raga S, Iglesias Alzueta J. [The Spanish Registry of Primary Immunodeficiencies. REDIP-1998]. Sangre (Barc). Apr 1999;44(2):163-7. [Medline].
Regueiro JR, Porras O, Lavin M. Ataxia-telangiectasia: a primary immunodeficiency revisted. Immunol Allergy Clin North Am. 2000;20:177-206.
Ruan QG, She JX. Autoimmune polyglandular syndrome type 1 and the autoimmune regulator. Clin Lab Med. Mar 2004;24(1):305-17. [Medline].
Sadighi Akha AA, Humphrey RL, Winkelstein JA, Loeb DM, Lederman HM. Oligo-/monoclonal gammopathy and hypergammaglobulinemia in ataxia-telangiectasia. A study of 90 patients. Medicine (Baltimore). Nov 1999;78(6):370-81. [Medline].
Schroeder SA, Swift M, Sandoval C, Langston C. Interstitial lung disease in patients with ataxia-telangiectasia. Pediatr Pulmonol. Jun 2005;39(6):537-43. [Medline].
Schwartz SA. Intravenous immunoglobulin treatment of immunodeficiency disorders. Pediatr Clin North Am. Dec 2000;47(6):1355-69. [Medline].
Taylor AM, Byrd PJ. Molecular pathology of ataxia telangiectasia. J Clin Pathol. Oct 2005;58(10):1009-15. [Medline].
Thampakkul S, Ballow M. Replacement intravenous immunoglobulin. Serum globulin therapy in patients with antibody immune deficiency. Immunol Aller Clin North Am. 2001;21:165.
Further Reading
Keywords
B-cell and T-cell combined disorders, B cell, T cell, combined B-cell and T-cell deficiency, ataxia-telangiectasia, AT, chronic mucocutaneous candidiasis, CMC, Nijmegen breakage syndrome, NBS
