Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A boy of Caucasian origin with a new subtype of autoimmune lymphoproliferative syndrome (ALPS) is described. The clinical picture was dominated by chronic noninfectious lymphadenopathy, splenomegaly, and recurrent bacterial infections. At the age of 6 the patient died of pneumococcal meningitis. Laboratory investigation disclosed impaired apoptosis in both B- and T-lymphocyte subsets and expanded populations of CD3+CD4-CD8- T lymphocytes. Furthermore, marked dysregulation of humoral immune responses with transient expansion of monoclonal B cells, corresponding monoclonal gammopathy, and the presence of autoantibodies was found. Functional and molecular analysis revealed that Fas protein expression was normal, a mutation in the Fas gene was not found. Moreover, transcription of the downstream effector caspase-10 was unremarkable. This patient is unique compared to previously described patients as severe humoral immunodeficiency and monoclonal gammopathy are usually not described in patients with ALPS. This case points out the important role of apoptosis in regulating the degree of humoral immune responses at a clonal level in humans and gives further evidence for the phenotypic diversity of ALPS.
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PMID:Autoimmune lymphoproliferative syndrome associated with severe humoral immunodeficiency and monoclonal gammopathy. 1210 64

Apoptosis is a form of programmed cell death that is controlled by aspartate-specific cysteine proteases called caspases. In the immune system, apoptosis counters the proliferation of lymphocytes to achieve a homeostatic balance, which allows potent responses to pathogens but avoids autoimmunity. The CD95 (Fas, Apo-1) receptor triggers lymphocyte apoptosis by recruiting Fas-associated death domain (FADD), caspase-8 and caspase-10 proteins into a death-inducing signalling complex. Heterozygous mutations in CD95, CD95 ligand or caspase-10 underlie most cases of autoimmune lymphoproliferative syndrome (ALPS), a human disorder that is characterized by defective lymphocyte apoptosis, lymphadenopathy, splenomegaly and autoimmunity. Mutations in caspase-8 have not been described in ALPS, and homozygous caspase-8 deficiency causes embryonic lethality in mice. Here we describe a human kindred with an inherited genetic deficiency of caspase-8. Homozygous individuals manifest defective lymphocyte apoptosis and homeostasis but, unlike individuals affected with ALPS, also have defects in their activation of T lymphocytes, B lymphocytes and natural killer cells, which leads to immunodeficiency. Thus, caspase-8 deficiency in humans is compatible with normal development and shows that caspase-8 has a postnatal role in immune activation of naive lymphocytes.
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PMID:Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. 1235 64