Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted a literature review to investigate the recent advances in genetics, molecular biology, clinical manifestations, and therapy of 7 inherited diseases that are characterized by seemingly unprovoked inflammation. These autoinflammatory diseases include familial Mediterranean fever; tumor necrosis factor receptor-associated periodic syndrome; hyperimmunoglobulinemia D with periodic fever syndrome; pyogenic arthritis, pyoderma gangrenosum, and acne syndrome; and the 3 cryopyrinopathies: neonatal-onset multisystem inflammatory disease/chronic infantile neurologic cutaneous and arthropathy syndrome, familial cold autoinflammatory syndrome, and Muckle-Wells syndrome. Recent identification of the susceptibility genes for autoinflammatory diseases has broadened the clinical spectrum as well as the molecular basis of these diseases. The cryopyrinopathies represent a continuum of diseases associated with mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene that encodes cryopyrin. Cryopyrin and pyrin (protein mutated in familial Mediterranean fever) belong to the family of PYRIN domain-containing proteins. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome is associated with mutations in the gene that encodes for CD2-binding protein 1 (CD2BP1), which binds pyrin. Recent studies have shown that activation of the interleukin 1beta pathway is a common mechanism in the pathogenesis of autoinflammatory diseases, further unifying these diseases. Recent advances in genetics and molecular biology have advanced our understanding of the pathogenesis of autoinflammatory diseases. Understanding autoinflammatory diseases will further our knowledge of cutaneous as well as systemic inflammation. Anakinra, a recombinant human interleukin 1 receptor antagonist, is a promising new biologic agent for the treatment of cryopyrinopathies as well other autoinflammatory diseases, such as tumor necrosis factor receptor-associated periodic syndrome and hyperimmunoglobulinemia D with periodic fever syndrome.
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PMID:Autoinflammatory diseases: clinical and genetic advances. 1834 98

Rilonacept (IL-1 Trap/Arcalyst) is a long-acting interleukin-1 (IL-1) blocker developed by Regeneron Pharmaceuticals. Initially, Regeneron entered into a joint development effort with Novartis to develop rilonacept for the treatment of rheumatoid arthritis (RA) but this was discontinued following the review of phase II clinical data showing that IL-1 blockade appeared to have limited benefit in RA. In February 2008, Regeneron received Orphan Drug approval from the Food and Drug Administration for rilonacept in the treatment of two cryopyrin-associated periodic syndromes (CAPS) disorders, namely, familial cold-induced autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS), for children and adults 12 years and older. CAPS is a group of inherited inflammatory disorders consisting of FCAS, MWS, neonatal-onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurologic, cutaneous and articular (CINCA) syndrome, all associated with heterozygous mutations in the NLRP3 (CIAS1) gene, which encodes the protein NLRP3 or cryopyrin. Prior to the discovery of the NLRP3 (CIAS1) mutations and the advent of IL-1-targeted therapy, treatment was aimed at suppressing inflammation but with limited success. The dramatic success of selective blockade of IL-1beta, initially with the IL-1 receptor antagonist (IL-1Ra; Kineret(R) or anakinra/ Amgen, Inc.), not only provided supportive evidence for the role of IL-1beta in CAPS but also demonstrated the efficacy of targeting IL-1beta for treatment of these conditions. A high-affinity protein called rilonacept has been produced by cytokine Trap technology and was developed by Regeneron. The desirable longer half-life of rilonacept offers potential alternatives to patients who do not tolerate daily injections very well or have difficulty with drug compliance. The initial evidence for the beneficial effects of rilonacept for MWS and FCAS suggests that it would also be a suitable treatment for CNICA/NOMID. It is yet to be determined whether rilonacept would be an effective treatment for other chronic inflammatory conditions such as gout, familial Mediterranean fever and systemic juvenile idiopathic arthritis.
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PMID:Rilonacept in the treatment of chronic inflammatory disorders. 1964 32

Objective: To describe the pregnancy course and outcome, and use of anakinra, a recombinant selective IL-1 receptor blocker, during pregnancy in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal onset multi-system inflammatory disease (NOMID). Methods: Women currently enrolled in natural history protocols (NCT00059748, and/or NCT00069329 under IND) who have been pregnant were included. Subjects underwent a structured, standardized interview with regards to maternal health, pregnancy and fetal outcomes. Medical records were reviewed. Results: Nine women (four with FCAS, one with MWS and four with NOMID) reported one to four pregnancies, each resulting in a total of fifteen FCAS, three MWS, and six NOMID pregnancies. Six births from FCAS mothers and three births from NOMID mothers occurred while patients were receiving anakinra. If a woman became pregnant while taking anakinra, the pre-pregnancy anakinra dose was continued. Anakinra dose was increased during one twin pregnancy. No preterm births or serious complications of pregnancy were observed. One fetus of the twin pregnancy had renal agenesis and suffered fetal demise. Genetic testing showed the deceased twin carried the same NLRP3 c.785T>C, p.V262A mutation as the mother. The other twin is healthy and mutation negative. Conclusions: Anakinra was continued during pregnancy in women with CAPS and provided significant, persistent CAPS symptom relief while continuing to prevent the long-term sequelae of CAPS. Anakinra was well tolerated. Although a causal relation between anakinra and renal agenesis seems unlikely, further safety data are needed.
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PMID:Anakinra use during pregnancy in patients with cryopyrin-associated periodic syndromes (CAPS). 2522 1