Biomedical subjects

Jennifer Puck

Publications and source records attributed to Jennifer Puck.

5 recordsLinked to original sources

PubMed2006

Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee Meeting in Budapest, 2005.

Although relatively rare, primary immunodeficiency diseases (PIDs) provide an excellent window into the functioning of the immune system. In the late 1960s, observations on these diseases, with their associated infections and genetics, bisected the immune system into humoral immunity and cell-mediated immunity. These diseases also represent a challenge in their diagnosis and treatment. Beginning in 1970, a unified nomenclature for the then-known PIDs was created by a committee convoked by the World Health Organization. Since then, and later under the aegis of the International Union of Immunological Societies, an international committee of experts has met every 2 to 3 years to update the classification of PIDs. During the past 15 years, the molecular basis of more than 120 PIDs has been elucidated. This update results from the latest meeting of this committee in Budapest, Hungary, in June 2005, which followed 2 1/2 days of scientific discussions. As a result of this work, new entities have been included, and the nomenclature of some PIDs (specifically of the various forms of class-switch recombination defects, previously known as hyper-IgM syndromes) has been changed.

B-Lymphocytes↗

PubMed2005

Use of mycophenolate mofetil for chronic, refractory immune cytopenias in children with autoimmune lymphoproliferative syndrome.

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of apoptosis associated most often with heritable FAS mutations leading to lymphadenopathy, hypersplenism and chronic refractory autoimmune cytopenias. Mycophenolate mofetil (MMF) was used to treat cytopenias in 13 ALPS patients aged 9 months to 17 years from a cohort of 118 children (aged < 18 years) and 82 adults. Twelve responded for a median follow-up of 49 weeks (range 38-240 weeks), defined by maintenance of adequate blood counts and reduction in dosage or cessation of other immunosuppressive agents. This preliminary experience suggests that MMF may spare steroid usage in patients with ALPS-associated cytopenias.

Adolescent↗

PubMed2004

Primary immunodeficiency diseases: an update.

Although relatively rare, primary immune deficiency diseases (PIDs) provide an excellent window into the functioning of the immune system. In the late 1960s, observations on these diseases, with their associated infections and genetics, bisected the immune system into humoral immunity and cell-mediated immunity. These diseases also represent a challenge in their diagnosis and treatment. Beginning in 1970, a unified nomenclature for the then-known primary immunodeficiency diseases was created by a committee convened by the World Health Organization. Since then, and later under the aegis of the International Union of Immunological Societies, an international committee of experts has met every 2 to 3 years to update the classification of PIDs. During the past 15 years, the molecular basis of more than 100 PIDs has been elucidated. This update results from the latest meeting of this committee in Sintra, Portugal, June 2003, which followed 2(1/2) days of scientific discussions.

Animals↗

PubMed2004

Induction of apoptosis and activation of NF-kappaB by CD95 require different signalling thresholds.

Mutations in the death domain of the death receptor CD95 (APO-1/Fas) cause lymphoproliferation and autoimmune disease in both lpr(cg) mice and in patients with autoimmune lymphoproliferative syndrome (ALPS) type Ia. By testing lymphocytes from ALPS type Ia patients, comparing heterozygous with homozygous lpr(cg) mice and coexpressing wild-type and mutant CD95 receptors, we demonstrate that induction of apoptosis requires two wild-type alleles of CD95. By contrast, nuclear factor-kappaB (NF-kappaB) can be fully activated in cells expressing both a mutant and a wild-type CD95 allele, suggesting different thresholds to activate the two signalling pathways. This was confirmed by testing lymphocytes from heterozygous lpr mice, which showed reduced sensitivity to CD95-mediated apoptosis but normal activation of NF-kappaB when compared with wild-type mice. Mutations in CD95 may eliminate the tumour-suppressive function of CD95, at the same time allowing induction of survival or proliferative pathways, which could contribute to the increased risk for lymphoma seen in ALPS type Ia patients.

Alleles↗

PubMed2002

Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency.

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.

Apoptosis↗