Three monogenic diseases, with features of both autoinflammation and autoimmunity, were described... more Three monogenic diseases, with features of both autoinflammation and autoimmunity, were described for the first time in 2014. As well as providing insights into the molecular basis of several rare immunological disorders, the discoveries have implications for their diagnosis and treatment.
Associations have been reported between vitamin D receptor (VDR) gene polymorphisms, type 1 diabe... more Associations have been reported between vitamin D receptor (VDR) gene polymorphisms, type 1 diabetes, insulin secretion, and the insulin resistance syndrome. As VDR polymorphisms have no known functional significance, these findings may implicate a variant of the VDR gene or a locus in linkage disequilibrium with the VDR. We have examined VDR mRNA and VDR protein levels in relation to VDR polymorphisms (41 Bangladeshi subjects) and analyzed insulin secretory capacity (143 Bangladeshi subjects), allowing for other known determinants. Peripheral blood mononuclear cells (PBMCs) from subjects who had been genotyped for BsmI, ApaI, TaqI, and FokI VDR restriction fragment length polymorphisms were used for both total VDR mRNA quantitation (using TaqMan) and measurement of VDR protein levels (using a specific micro-immunoassay). Stepwise multiple regression analyses were used (to P < 0.05) to analyze the data. For the insulin secretion index, the best-fit model (n = 143, P < 0.0001) ...
Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology charac... more Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.
Background TNF receptor-associated periodic syndrome (TRAPS) is a recently defined dominantly inh... more Background TNF receptor-associated periodic syndrome (TRAPS) is a recently defined dominantly inherited autoinflammatory syndrome, which is caused by mutations in the extracellular domains of the 55 kDa TNF receptor, TNFRSF1A. TRAPS is characterised by periodic fevers, sterile peritonitis, pleurisy, arthritis, erysipeloid erythema of the skin, and conjunctivitis. Affected individuals have shown a shedding defect of TNFRSF1A upon stimulation and, consequently, low levels of soluble TNFRSF1A in serum. Objectives We studied a three-generation Finnish family, where recurrent attacks of fever and abdominal pain appeared to segregate as an autosomal dominant trait. Methods The TNFRSF1A gene was sequenced in both affected and unaffected family members. Flow cytometric analysis and ELISA analyses were used to assess membrane expression and serum levels of TNFRSF1A, respectively. Results A missense mutation of exon 4, resulting in an amino acid substitution (F112I) close to a conserved cyste...
Three monogenic diseases, with features of both autoinflammation and autoimmunity, were described... more Three monogenic diseases, with features of both autoinflammation and autoimmunity, were described for the first time in 2014. As well as providing insights into the molecular basis of several rare immunological disorders, the discoveries have implications for their diagnosis and treatment.
Associations have been reported between vitamin D receptor (VDR) gene polymorphisms, type 1 diabe... more Associations have been reported between vitamin D receptor (VDR) gene polymorphisms, type 1 diabetes, insulin secretion, and the insulin resistance syndrome. As VDR polymorphisms have no known functional significance, these findings may implicate a variant of the VDR gene or a locus in linkage disequilibrium with the VDR. We have examined VDR mRNA and VDR protein levels in relation to VDR polymorphisms (41 Bangladeshi subjects) and analyzed insulin secretory capacity (143 Bangladeshi subjects), allowing for other known determinants. Peripheral blood mononuclear cells (PBMCs) from subjects who had been genotyped for BsmI, ApaI, TaqI, and FokI VDR restriction fragment length polymorphisms were used for both total VDR mRNA quantitation (using TaqMan) and measurement of VDR protein levels (using a specific micro-immunoassay). Stepwise multiple regression analyses were used (to P < 0.05) to analyze the data. For the insulin secretion index, the best-fit model (n = 143, P < 0.0001) ...
Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology charac... more Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.
Background TNF receptor-associated periodic syndrome (TRAPS) is a recently defined dominantly inh... more Background TNF receptor-associated periodic syndrome (TRAPS) is a recently defined dominantly inherited autoinflammatory syndrome, which is caused by mutations in the extracellular domains of the 55 kDa TNF receptor, TNFRSF1A. TRAPS is characterised by periodic fevers, sterile peritonitis, pleurisy, arthritis, erysipeloid erythema of the skin, and conjunctivitis. Affected individuals have shown a shedding defect of TNFRSF1A upon stimulation and, consequently, low levels of soluble TNFRSF1A in serum. Objectives We studied a three-generation Finnish family, where recurrent attacks of fever and abdominal pain appeared to segregate as an autosomal dominant trait. Methods The TNFRSF1A gene was sequenced in both affected and unaffected family members. Flow cytometric analysis and ELISA analyses were used to assess membrane expression and serum levels of TNFRSF1A, respectively. Results A missense mutation of exon 4, resulting in an amino acid substitution (F112I) close to a conserved cyste...
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