China
Africa
Explore chapters and articles related to this topic
Vasculitis
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Michelle L. Robinette, Eli Miloslavsky, Zachary S. Wallace
Adult-onset somatic mutations are of particular interest as a potential cause of vasculitis. Using a genotype-first approach, novel somatic myeloid-restricted mutations in UBA1 with high variant allelic frequency have been identified in men with severe adult-onset autoinflammatory syndromes, called the VEXAS syndrome (Table 10.2) (55). Other manifestations include hematologic malignancy and vasculitis typically characterized as PAN or GCA. Mechanistically, UBA1 mutations deregulate ubiquitination, a critical component across cell biology, including innate immune signaling, resulting in increased generation of pro-inflammatory cytokines, cellular stress, and unfolded protein response (UPR) (55). Similar mechanisms are implicated in germline forms of monogenic vasculitis, including DADA2, COPA, and SAVI (65, 66). Somatic mutations have also been recently identified in Sjögren’s syndrome–associated cryoglobulinemic vasculitis, with several lymphoma driver mutations identified in B cell lineages during the transition of benign rheumatoid factor (RF) into pathogenic cryoglobulinemic RF (67).
Phagocytic cells and their functions
Published in Gabriel Virella, Medical Immunology, 2019
Gabriel Virella, John W. Sleasman
Cold autoinflammatory syndromes (cryopyrin-associated periodic syndromes [CAPS]) are hereditary autosomic-dominant diseases characterized by nonpruritic urticarial, arthritis, fever, and leukocytosis after cold exposure. The predominant genetic defect is within the NLRP3 gene, resulting in gain of function and constitutional hyperactivity of the inflammasome. This results in abnormally high production of IL-1β due to alterations of cryopyrin inflammasomes by abnormal NLRP3 signaling. Treatment consists of drugs that prevent IL1-β signaling, such as anakinra, rilonacept, and canakinumab.
Generalized pustular psoriasis
Published in M. Alan Menter, Caitriona Ryan, Psoriasis, 2017
Recent genetic discoveries led to the inclusion of GPP in the range of autoinflammatory syndromes, a spectrum of genetically inherited, innate immune-mediated disorders. These major advances are likely to lead to the development of truly tailored therapies in the very close future.
JAK inhibitors in rheumatology
Published in Immunological Medicine, 2023
Treatment outcomes in autoinflammatory syndromes have also been reported, including 13 patients with Behcet’s disease treated with tofacitinib as an additional therapy [62] revealing that 6/13 (61.5%) patients achieved a partial response and 38.5% resulted with no response. Two patients out of 13 (15.4%) developed herpes zoster, but no other apparent treatment-related AEs were noted. A Literature review of the JAK inhibitor treatment of the Familial Mediterranean fever, another well-known autoinflammatory syndrome, reported a total of 6 cases in multiple reports [61]. All patients received tofacitinib alone or in combination with glucocorticoids or immunosuppressive agents. Fifty percent of the patients achieved complete remission, and the remaining 50% had ‘partial remission’ with residual inflammatory response but no worsening of symptoms without AEs.
Familial cold autoinflammatory syndrome with rheumatoid arthritis
Published in Baylor University Medical Center Proceedings, 2021
Brooke Walterscheid, Jeannie Nguyen, Swetha Gadwala, Goutam Shome, Michelle Tarbox, James A. Tarbox
Autoinflammatory syndromes present as recurrent, febrile episodes accompanied by various cutaneous, mucosal, serosal, and osteoarticular manifestations. Familial cold autoinflammatory syndrome (FCAS) is a cryopyrin-associated periodic syndrome caused by an overproduction of cytokines due to defects in inflammasomes1; it typically presents in infancy with episodic fever, skin rash, and joint pain after exposure to cold temperatures. FCAS is rare, with only 1 to 2 cases per million in the USA, and is caused by an autosomal dominant mutation in the NLRP3 gene at 1q44, leading to an overproduction of interleukin-1β by inflammasomes.2–4 Here, we discuss both FCAS and its even rarer associations with autoimmune disorders, including rheumatoid arthritis (RA) and amyloidosis.
Immune cell dynamics in response to an acute laboratory stressor: a within-person between-group analysis of the biological impact of early life adversity
Published in Stress, 2022
Laura Etzel, Abner T. Apsley, Brooke C. Mattern, Waylon J. Hastings, Thomas Heller, Nilam Ram, Sue Rutherford Siegel, Idan Shalev
Differences in immune cell dynamics as a function of ELA status were observed for a few cell types. The ELA group exhibited higher increases in total WBCs 30–90 minutes compared to the control group, irrespective of session. Examination of Figure 3 demonstrates that these differences in WBCs appear to be driven by differences in counts of neutrophils, basophils, and eosinophils, which all tended to be higher in the ELA group, although only differences in neutrophils were statistically significant. Differences in the trafficking of WBCs and immune subsets in response to stress can have health implications for individuals exposed to ELA. Neutrophils are the major pathogen fighting immune cells, functioning as regulators of innate and adaptive immune responses (Mayadas et al., 2014). Neutrophils are major contributors in the pathogenesis of various autoimmune diseases, autoinflammatory syndromes, and cardiovascular diseases (Dahdah et al., 2022; Kaplan, 2013; Wouters et al., 2021). Eosinophils are also involved in the immunological regulation of both innate and adaptive immunity (Wen & Rothenberg, 2016). Eosinophils are responsible for tissue damage and inflammation in many diseases and are involved in the development of type 2 diabetes and atherosclerosis (metabolic homeostasis) (Jacobsen et al., 2012), chronic diseases which individuals exposed to ELA are at increased susceptibility to develop (Rich-Edwards et al., 2010; Su et al., 2015). Basophils are involved in inflammatory responses, as well as the development of allergic diseases. Taken together, this may be indicative of chronic hyperactivity of the distinct elements of the immune system at rest and in response to acute stress in individuals with a history of ELA, as has been previously suggested (Danese et al., 2007).