Chapter category: Autoimmunity
CTLA-4 in Addison’s Disease
CTLA-4 in Autoimmune Disease
Edited by: Flemming PociotISBN: 1-58706-068-X
» Get more information about this book at landesbioscience.com «
Chapter authors:
Klaus Badenhoop
Addison’s disease is a rare autoimmune disorder of adrenal destruction leading to death if unrecognised and untreated. Usually non-surgical adrenal insufficiency is caused by either tuberculous granuloma, other infectious agents such as observed in AIDS or has no clear etiology in about 70-80% that is considered to be idiopathic. In this form of adrenal dysfunction the adrenal glands are atrophic and contain only few cortical cells. The adrenal medulla is usually spared from the destruction. In contrast the tuberculous adrenal disease leads to granuloma and caseation with subsequent calcification. Idiopathic adrenal insufficiency is in most cases due to autoimmune destruction of adrenocortical cells: antibodies against adrenal cells and the adrenal autoantigen steroid-21-hydroxylase are detected in the majority (80%) of newly manifested patients.1 A recently developed radiobinding assay has been reported to be highly sensitive and specific for Addison’s disease.2 As in other autoimmune endocrinopathies, there is a genetic susceptibility conferred by several gene loci. Immune destruction of adrenal cells is marked by an infiltration of autoreactive T-cells and the appearance of antibodies directed against intracellular enzymes such as 21- and 17-•-hydroxylases. Patients may present with mild weakness and malaise that—if underestimated—would become a problem of medical neglicence that may even happen in precomatous patients. Once the diagnosis is confirmed by low cortisol levels after ACTH stimulation, patients are treated with life-long glucocorticoid and mineralocorticoid substitution therapy. Since this disease is still underrecognised, exact figures of incidence and prevalence are lacking. However in Italy and in the UK such calculations have been performed: Laureti et al have calculated the prevalence of Addison’s disease to be in the order of 117 per million in Umbria,3 whereas Kong and Jeffcoate had previously reported 110 per million in Nottingham UK with an incidence of 5.6 per million.4 Through affected patients one can identify antibody positive relatives with still normal adrenal function that are presymptomatic individuals at high risk for Addison’s disease.
Additional chapters from this book:
CTLA-4: Its Role in Transplant Tolerance and Rejection
David M. Rothstein and Fadi G. Lakkis
Transplantation is the treatment of choice for end-stage heart, kidney, liver, and pancre atic islet disease. Current strategies require life-long immunosuppression in attempts to inhibit the alloim...
CTLA-4 in Type 1 Diabetes Mellitus
Lorenza Nisticò, Isabella Cascino, Raffaella Buzzetti and Paolo Pozzilli
The current etiological classification defines type 1 diabetes as a chronic hyperglycemia due to a cellular mediated immune destruction of the insulin-secreting pancreatic beta-cells. This disease i...
CTLA-4 in Addison’s Disease
Klaus Badenhoop
Addison’s disease is a rare autoimmune disorder of adrenal destruction leading to death if unrecognised and untreated. Usually non-surgical adrenal insufficiency is caused by either tuberculous gran...
CTLA-4 in Multiple Sclerosis
Rebecca J. Greenwald, Yvette Latchman and Arlene H. Sharpe
The B7:CD28/CTLA-4 pathway has a pivotal role in regulating T cell immune responses and manipulation of this key immunoregulatory pathway may lead to the development of therapeutic interventions to ...
CTLA-4 in Myasthenia Gravis
Ann Kari Lefvert
Myasthenia gravis (MG) is commonly regarded as the prototype for an organ specific antibody-mediated autoimmune disease. The disease is characterized by an immune response against the nicotinic acet...
CTLA-4 in Rheumatoid Arthritis
Peter P. Sfikakis and Stamatis-Nick Liossis
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease characterised by symmetric polyarthritis of the small joints of the hands and feet and the larger appendicular joints. The etiol...
CTLA-4 in Systemic Lupus Erythematosus
David I. Daikh and David Wofsy
The recent characterization of several costimulatory interactions between antigen presenting cells and T cells represents a major advance in our understanding of both normal adaptive immune response...
CTLA-4: Its Role in the Immune Response
Maria-Luisa Alegre and Thomas F. Gajewski
T lymphocytes are essential for host defense against many viral or parasitic infections, and also contribute to defense against tumors. In addition, T cells mediate rejection of transplanted organs,...
Autoimune Disorders—A Common Link?
Flemming Pociot
The immune system has evolved to protect multicellular organisms from pathogens. It is therefore perplexing that this system turns on the individual, in some cases precipitating catastrophic autoimm...
