Autoimmunity in human primary immunodeficiency diseases

Arkwright, Peter D.; Abinun, Mario; Cant, Andrew J.

doi:10.1182/blood.v99.8.2694

Cited by 162 publications

(119 citation statements)

References 122 publications

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“…20 However, the underlying diagnosis of PID is a wellrecognised predisposing factor for the development of autoimmune disease even in very young children. 21 Patients with WAS, in particular, are prone to developing a wide spectrum of autoimmune disorders but there was no autoimmune thyroid disease reported in the two large patient series recently published. 22,23 In addition to the altered immune function due to the underlying immunodeficiency, [21][22][23] a haplotype that is associated with autoimmune illness (HLA DQ2 and/or DQ8) may predispose to thyroid dysfunction post-BMT.…”

Section: Discussionmentioning

confidence: 99%

“…21 Patients with WAS, in particular, are prone to developing a wide spectrum of autoimmune disorders but there was no autoimmune thyroid disease reported in the two large patient series recently published. 22,23 In addition to the altered immune function due to the underlying immunodeficiency, [21][22][23] a haplotype that is associated with autoimmune illness (HLA DQ2 and/or DQ8) may predispose to thyroid dysfunction post-BMT. 24 In contrast to this, autoimmune thyroid damage and hypothyroidism have been reported in infants with combined PID such as IPEX (immunodeficiency, polyendocrinopathy, enteropathy, X-linked) 25 and Omenn syndrome.…”

Section: Discussionmentioning

confidence: 99%

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Thyroid dysfunction after bone marrow transplantation for primary immunodeficiency without the use of total body irradiation in conditioning

Slatter

Gennery

Cheetham

et al. 2004

Bone Marrow Transplant

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Summary:Thyroid dysfunction, a common long-term complication following bone marrow transplantation (BMT), is frequently associated with total body irradiation (TBI) given in the pre-BMT conditioning protocol. We report our preliminary observation of the prevalence of thyroid dysfunction in children transplanted for primary immunodeficiency (PID) who were given cytoreductive conditioning with busulphan and cyclophosphamide, but without TBI. We evaluated thyroid-stimulating hormone (TSH) and free thyroxine (fT4) in 83 survivors transplanted between 1987 and 2002. We found nine children (10.8%) with clinical and/or biochemical thyroid dysfunction at 4 months to 4.5 years post-BMT of which three had positive antithyroid microsomal antibodies. Two patients were classified as primary and seven as compensated hypothyroidism (hyperthyrotropinaemia). Four patients with clinical features of hypothyroidism received replacement thyroxine, while five of the seven patients with compensated hypothyroidism remain off thyroxine because we suspect this may be a transient phenomenon. Abnormalities of thyroid function including severe primary hypothyroidism may occur post-BMT in children receiving chemotherapy conditioning without TBI. Thyroid function should be assessed regularly in this group of patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Thyroid dysfunction after bone marrow transplantation for primary immunodeficiency without the use of total body irradiation in conditioning

Slatter

Gennery

Cheetham

et al. 2004

Bone Marrow Transplant

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“…A central question in understanding the pathophysiology of WAS is why immunodeficient patients develop symptoms suggestive of hyperactivation of immune compartments, including eczema and autoimmune diseases (5,10). It has recently been recognized that CD4 + CD25 + Treg cells play an important role in the negative regulation of immune responses and the prevention of autoimmunity (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Impaired in vitro regulatory T cell function associated with Wiskott–Aldrich syndrome

Adriani

Aoki

Horai

et al. 2007

Clinical Immunology

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Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency characterized by the contradictory coexistence of impaired T-cell function and exaggerated T-cell-mediated pathology, including autoimmunity and eczema. WAS protein (WASp)-deficient mice are also immunodeficient and can develop autoimmune disease. Since defects in regulatory T-cells (Treg) are associated with autoimmunity, we examined the presence and function of these cells in WAS patients and WASpdeficient mice. We found that CD4 + CD25 + FOXP3 + Treg cells can develop in the absence of WASp expression. However, Treg cells both from WASp-deficient mice and from four out of five WAS patients studied showed impaired in vitro suppressor function. In WASp-deficient mice, this defect could be partially rescued by pre-activation with IL-2, suggesting that inadequate cell activation may play a role in WASp-deficient Treg dysfunction. These findings may provide insights into the complex pathophysiology and paradoxical phenotypes of WAS and suggest new therapeutic modalities for autoimmunity in these patients.

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“…Immune deficiencies are associated with an increased incidence of autoimmune disease [48], and the incidence of autoimmunity is increased in DiGeorge syndrome [42,49]. Autoimmune diseases including autoimmune cytopenias [50,51], autoimmune arthritis [52] and autoimmune endocrinopathy [53] have been described.…”

Section: Autoimmunitymentioning

confidence: 99%

Immunodeficiency and Autoimmunity in 22q11.2 Deletion Syndrome

2007

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22q11.2 deletion syndrome is the commonest chromosome deletion syndrome. 22q11.2 deletion may result in variable clinical phenotypes which may differ even between patients with identical deletions. Abnormal pharyngeal arch development results in defects in the development of the parathyroid glands, thymus and conotruncal region of the heart. Defective thymic development is associated with impaired immune function. ‘Complete’ DiGeorge syndrome with total absence of the thymus and a severe T‐cell immunodeficiency accounts for <0.5% of patients. The majority of patients with 22q11.2 deletion syndromes have ‘partial’ defects with impaired thymic development rather than complete absence with variable defects in T‐cell numbers. Immunodeficiency in these patients is not solely due to T‐cell deficiency and abnormalities of T‐cell clonality or impairment of proliferative responses may play a role. Humoral deficiencies including defects in the B‐cell compartment have also been identified in these patients. 22q11.2 deletion syndrome patients are at increased risk of a variety of autoimmune diseases. A number of immune defects may predispose to the development of autoimmunity in these patients including increased infection, impaired development of natural T‐regulatory cells and impaired thymic central tolerance.

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Autoimmunity in human primary immunodeficiency diseases

Cited by 162 publications

References 122 publications

Thyroid dysfunction after bone marrow transplantation for primary immunodeficiency without the use of total body irradiation in conditioning

Thyroid dysfunction after bone marrow transplantation for primary immunodeficiency without the use of total body irradiation in conditioning

Impaired in vitro regulatory T cell function associated with Wiskott–Aldrich syndrome

Immunodeficiency and Autoimmunity in 22q11.2 Deletion Syndrome

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