A novel knock-in mouse model of cryopyrin-associated periodic syndromes with development of amyloidosis: Therapeutic efficacy of proton pump inhibitors

Phenocopies: Mimics of Inborn Errors of Immunity

“…NLR contains a pyrin domain such as NLRP3 and/or caspase activation domains (CARD), which promotes its self-assembly, some NLRs form multiprotein complexes called inflammasomes, which protect the cell from injuries as well as regulate homeostasis. The gain-of-function mutations in NLRP3 cause hyperactivation of cryopyrininflammasome and thus cause disease manifestations [31] [32].…”

“…Symptoms are triggered by exposure to cold (described at temperatures below 72˚F for more than 30 minutes), exacerbations have a chronic course and vary from 1 to 3 days. Table 3 shows the characteristics that can help differentiate these syndromes [31] [34].…”

“…In laboratory studies, patients present with leukocytosis and during exacerbations, neutrophiliais found, there is a little elevation of acute phase reactants. Open Access Library Journal Skin biopsy may show edema and neutrophilic infiltrate in the dermis [31]. The findings in imaging studies such as magnetic resonance, the IRM of the central nervous system have shown a decrease in the T2 signal in the cochlea and brain, which is related to the loss of sensory hearing in these patients [35] [36].…”

Autoinflammatory disease: New mouse models and therapies

“…1 The article by Bertoni et al 2 in this month's issue of The Journal of Allergy and Clinical Immunology is the latest in a series of reports of mouse models of CAPS mimicking human disease and NLRP3-targeted therapies that could be applied to patients with CAPS. 2 The authors use a well-established knockin approach to express a known human CAPS mutation at the severe end of the human disease continuum (NOMID) in murine Nlrp3. Similar to previous CAPS models, the mice show evidence of systemic inflammation with rash, poor weight gain, peripheral leukocytosis, increased serum cytokines, splenomegaly, inflammatory cell infiltrates in several tissues, and reduced survival.…”

“…3,4 Each of the models has a unique CAPS disease mutation, but different recombinant designs (Table I). [2][3][4][5][6] Bertoni et al chose a mutation associated with the most severe CAPS phenotype and used a strategy for developing their mouse that is very similar to that used by Brydges et al in 3 previously published CAPS mouse models with conditional expression of the Nlrp3 mutation. 3,4 Although the authors did not take advantage of this feature for the current article, the use of this construct does allow for a potential comparison between the 4 murine models with different CAPS mutations along the disease spectrum, with implications for mutation-specific molecular mechanisms or response to therapies.…”