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      Review: Cytokine Storm Syndrome: Looking Toward the Precision Medicine Era : CYTOKINE STORM SYNDROME IN THE PRECISION MEDICINE ERA

      1 , 2
      Arthritis & Rheumatology
      Wiley

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          Adult-Onset Immunodeficiency in Thailand and Taiwan

          New England Journal of Medicine, 367(8), 725-734
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            The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses.

            Pathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as damage-associated molecular patterns or alarmins, remains ill defined. We show that interleukin-33 (IL-33), an alarmin released from necrotic cells, is necessary for potent CD8(+) T cell (CTL) responses to replicating, prototypic RNA and DNA viruses in mice. IL-33 signaled through its receptor on activated CTLs, enhanced clonal expansion in a CTL-intrinsic fashion, determined plurifunctional effector cell differentiation, and was necessary for virus control. Moreover, recombinant IL-33 augmented vaccine-induced CTL responses. Radio-resistant cells of the splenic T cell zone produced IL-33, and efficient CTL responses required IL-33 from radio-resistant cells but not from hematopoietic cells. Thus, alarmin release by radio-resistant cells orchestrates protective antiviral CTL responses.
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              Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series.

              To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA). Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome. Among 46 patients meeting inclusion criteria, anakinra monotherapy was used in 10 patients (22%), while 67% received corticosteroids and 33% received additional DMARDs. Outcomes were evaluated at a median followup interval of 14.5 months. Fever and rash resolved within 1 month in >95% of patients, while C-reactive protein and ferritin normalized within this interval in >80% of patients. Active arthritis persisted at 1 month in 39% of patients, at 3 months in 27%, and at >6 months of followup in 11%. Approximately 60% of patients, including 8 of 10 receiving anakinra monotherapy, attained a complete response without escalation of therapy. Disease characteristics and treatment were similar in partial and complete responders, except that partial responders were markedly younger at onset (median age 5.2 years versus 10.2 years; P = 0.004). Associated adverse events included documented bacterial infection in 2 patients and hepatitis in 1 patient. Tachyphylaxis was not observed. Anakinra as first-line therapy for systemic JIA was associated with rapid resolution of systemic symptoms and prevention of refractory arthritis in almost 90% of patients during the interval examined. These results justify further study of IL-1 inhibition as first-line, rather than rescue, therapy in systemic JIA. Copyright © 2011 by the American College of Rheumatology.
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                Author and article information

                Journal
                Arthritis & Rheumatology
                Arthritis & Rheumatology
                Wiley
                23265191
                June 2017
                June 2017
                May 30 2017
                : 69
                : 6
                : 1135-1143
                Affiliations
                [1 ]Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine; Philadelphia
                [2 ]Weill Cornell Medical College; New York New York
                Article
                10.1002/art.40071
                28217930
                4d04a295-9d0f-4bf9-b676-b0f4e1271e90
                © 2017

                http://doi.wiley.com/10.1002/tdm_license_1

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