Chapter category: Autoimmunity
CTLA-4 in Type 1 Diabetes Mellitus
CTLA-4 in Autoimmune Disease
Edited by: Flemming PociotISBN: 1-58706-068-X
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Chapter authors:
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 is characterized by the presence at the onset of antibodies against insular molecules (islet cell antibodies (ICA), anti-insulin (IAA), anti-glutamic acid decarboxylase (GADA) and anti-tyrosine phosphatase (IA-2) and by a susceptible genotype at the HLA class II DRB1 and DQB1 genes. There is no cure and diabetic subjects require lifetime daily multiple injections of insulin to maintain glucose homeostasis. Type 1 diabetes occurs in both sexes, but a slight male excess has been found in some populations.1 Incidence data are available for children up to 14 years of age in 50 countries of the five continents and show a striking variation among populations and within the population of the same country. The age-adjusted incidence rates range from 0.1/100,000 per year in China and Venezuela to ~37/100,000 per year in Sardinia and Finland.1 It is widely accepted that type 1 diabetes results from interaction of a polygenic trait with environmental risk factors. This hypothesis has received support from different observations. Approximately one-tenth of the cases occurs in families and identical twins (that share the same genome, except for mitochondrial DNA, post-zygotic and epigenetic DNA changes) are more often concordant for the disease than dizygotic twins (that share half genome) thus suggesting the existence of inherited factors.2-4 On the other hand, concordance is below 100% in identical twins indicating that a susceptible genome is not sufficient to develop the disease. Moreover, it is also likely that identical twins share more of their environment than non-identical twins. The contribution of genetic susceptibility has been underlined by assessment of the incidence of type 1 diabetes in children of migrants from high incidence to low incidence regions. Two studies have demonstrated that children of Sardinian heritage born and resident in Lazio and Lombardy (two Italian regions with incidence ~8/100,000 per year) have the same fourfold higher incidence as the population of origin. Moreover, children born in continental Italy of mixed couples with one Sardinian partner have an intermediate rate between those of Sardinia and of continental Italy.5,6
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...
