Systemisch inflammatorische Erkrankungen als Differenzialdiagnose in der Neugeborenenperiode – Inflammasom-vermittelte Erkrankungen

Zusammenfassung

Autoinflammatorische Erkrankungen sind durch systemische oder organbezogene Entzündung gekennzeichnet, welche zumindest initial von fehlregulierten Mechanismen des angeborenen Immunsystems ausgehen. Einige monogene autoinflammatorische Erkrankungen manifestieren in der Perinatalperiode, sodass sie Differenzialdiagnosen zu Infektionen des Neugeborenen darstellen. Im vorliegenden Artikel werden Einblicke in die klinische Präsentation und die molekulare Pathophysiologie Inflammasom-vermittelter monogener Erkrankungen mit Manifestation im Neugeborenenalter gegeben.

Summary

Autoinflammatory conditions are characterized by systemic or organ specific inflammation which is at least initially caused by dysregulation of innate immune mechanisms. Several monogenic autoinflammatory conditions manifest in the perinatal period which makes them differential diagnoses to infections of the newborn. Here, an overview of the clinical presentation and molecular pathophysiology of inflammasome-associated monogenic disorders with manifestation in the newborn period will be given.

Schlüsselwörter

Autoinflammation - Diagnose - Inflammation - Inflammasom - NLRP3 - NLRC4 - CNO - Majeed - DIRA - Biomarker - Therapie

Keywords

Autoinflammation - diagnosis - inflammation - inflammasome - NLRP3 - NLRC4 - CNO - Majeed - DIRA - biomarker - therapy

• Literatur

• 1 McDermott MF, Aksentijevich I, Galon J. et al. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 1999; 97 (01) 133-144.
• 2 Hedrich CM. Shaping the spectrum - From autoinflammation to autoimmunity. Clin Immunol 2016; 165: 21-28.
• 3 de Jesus AA, Canna SW, Liu Y, Goldbach-Mansky R. Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling. Annu Rev Immunol 2015; 33: 823-874.
• 4 McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med 2006; 03 (08) e297.
• 5 Aksentijevich I, Nowak M, Mallah M. et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum 2002; 46 (12) 3340-3348.
• 6 Canna SW, de Jesus AA, Gouni S. et al. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet 2014; 46 (10) 1140-1146.
• 7 Duncan JA, Canna SW. The NLRC4 Inflammasome. Immunol Rev 2018; 281 (01) 115-123.
• 8 Romberg N, Vogel TP, Canna SW. NLRC4 inflammasomopathies. Curr Opin Allergy Clin Immunol 2017; 17 (06) 398-404.
• 9 Winkler S, Hedrich CM, Rosen-Wolff A. [Caspase-1 regulates autoinflammation in rheumatic diseases]. Z Rheumatol 2016; 75 (03) 265-275.
• 10 Winkler S, Rosen-Wolff A. Caspase-1: an integral regulator of innate immunity. Semin Immunopathol 2015; 37 (04) 419-427.
• 11 El-Shanti H, Ferguson P. et al. Majeed Syndromex. Adam MP, Ardinger HH, Pagon RA. et al. lHrsg. GeneReviews®. Seattle, WA: 1993
• 12 El-Shanti HI, Ferguson PJ. Chronic recurrent multifocal osteomyelitis: a concise review and genetic update. Clin Orthop Relat Res 2007; 462: 11-19.
• 13 Morbach H, Hedrich CM, Beer M, Girschick HJ. Autoinflammatory bone disorders. Clin Immunol 2013; 147 (03) 185-196.
• 14 Aksentijevich I, Masters SL, Ferguson PJ. et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med 2009; 360 (23) 2426-2437.
• 15 Aksentijevich I, Putnam CD, Remmers EF. et al. The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum 2007; 56 (04) 1273-1285.
• 16 Goldbach-Mansky R. Current status of understanding the pathogenesis and management of patients with NOMID/CINCA. Curr Rheumatol Rep 2011; 13 (02) 123-131.
• 17 Grinstein L, Endter K, Hedrich CM. et al. An optimized whole blood assay measuring expression and activity of NLRP3, NLRC4 and AIM2 inflammasomes. Clin Immunol. 2017
• 18 Tanaka N, Izawa K, Saito MK. et al. High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome: results of an International Multicenter Collaborative Study. Arthritis Rheum 2011; 63 (11) 3625-3632.
• 19 Jesus AA, Goldbach-Mansky R. IL-1 blockade in autoinflammatory syndromes. Ann Rev Med 2014; 65: 223-244.
• 20 Canna SW, Girard C, Malle L. et al. Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition. J Allergy Clin Immunol 2017; 139 (05) 1698-1701.
• 21 Schnellbacher C, Ciocca G, Menendez R. et al. Deficiency of interleukin-1 receptor antagonist responsive to anakinra. Pediatr Dermatol 2013; 30 (06) 758-760.
• 22 Lorden G, Sanjuan-Garcia I, de Pablo N. et al. Lipin-2 regulates NLRP3 inflammasome by affecting P2X7 receptor activation. J Exp Med 2017; 214 (02) 511-528.
• 23 Hofmann SR, Kapplusch F, Girschick HJ. et al. Chronic Recurrent Multifocal Osteomyelitis (CRMO): Presentation, Pathogenesis, and Treatment. Curr Osteoporos Rep 2017; 15 (06) 542-554.
• 24 Herlin T, Fiirgaard B, Bjerre M. et al. Efficacy of anti-IL-1 treatment in Majeed syndrome. Ann Rheum Dis 2013; 72 (03) 410-413.