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DOI: 10.1055/s-0037-1618368
Frühe Diagnostik des systemischen Lupus erythematodes
Klinische, serologische und genetische ParameterEarly diagnosis of systemic lupus erythematosusClinical, serological and genetic parametersPublication History
Publication Date:
27 December 2017 (online)
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Zusammenfassung
Die frühe Diagnose eines systemischen Lupus erythematodes (SLE) fußt noch immer in erster Linie auf einer sorgfältigen klinischen Erfassung typischer ACR-Kriterien ( 4) durch den behandelnden Arzt. Hinzu tritt die anamnestische Eruierung charakteristischer Auslösesituationen wie Jahreszeit (Frühjahr, Sommer), Sonneneinfluss, Virusinfekte, Medikamente und Gewebstraumata. Ergänzend fordern die ACR-Kriterien den Nachweis SLEtypischer Autoantikörper mit Spezifität für Kernantigene (ANA), dsDNA, Sm, rib1, [uni03B2]2GP1. Diagnosestützend sind Befunde eines gesteigerten intravasalen Complement-Umsatzes (niedrige CH50, erhöhtes C3d). Im Validierungsstadium für eine SLE-Frühdiagnose befinden sich Tests zur Erfassung einer Typ-1-IFN-Signatur wie z. B. eine standardisierte qPCR-Reaktion für den Nachweis von sechs durch INF-[uni03B1] induzierte Gene in Blutleukozyten („total IFN score for the diagnosis of SLE“).
Summary
In early diagnosis of SLE careful recording of typical clinical ACR criteria ( 4) by the treating physician remains a mainstay. Anamnestic revelation of characteristic flare inducing circumstances such as spring season, sun exposure, viral infections, certain drugs and tissue damage are supportive of an SLE diagnosis. Detection of SLE-typical autoanti-bodies with specificity for nuclear antigens (ANA), dsDNA, Sm, rib1 and [uni03B2]2-GP1 are requested by the ACR criteria whereas increased intravascular complement turnover (low CH50, elevated C3d) contributes indirect, supportive evidence. Currently measurements of an increased type 1 INF signature, such as a qPCR of six leukocyte genes induced by IFN-[uni03B1] (“total IFN score for the diagnosis of SLE”) are under clinical validation.
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Literatur
- 1 Tan EM, Cohen AS, Fries JF. et al The 1982 revised criteria for the classifi cation of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-1277.
- 2 Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40 (09) 1725
- 3 Feletar M, Ibañez D, Urowitz MB, Gladman DD. The impact of the 1997 update of the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus: what has been changed?. Arthritis Rheum 2003; 48 (07) 2067-2069.
- 4 Mueller-Ladner U. Systemischer Lupus erythematodes. In Peter HH, Pichler W, Mueller-Ladner U. Hrsg. Klinische Immunologie, 3. Auflage.. München: Elsevier; 2012: 311-331.
- 5 Gromnica-Ihle E. Das Antiphospholipidsyndrom. In Peter HH, Pichler W, Mueller-Ladner U. Hrsg. Klinische Immunologie, 3. Auflage.. München: Elsevier; 2012: 331-336.
- 6 Oglesby A, Korves C, Laliberté F. et al Impact of early versus late systemic lupus erythematosus diagnosis on clinical and economic outcomes. Appl Health Econ Health Policy 2014; 12 (02) 179-190.
- 7 Kasitanon N, Intaniwet T, Wangkaew S. et al. The clinically quiescent phase in early-diagnosed SLE patients: inception cohort study. Rheumatology (Oxford) 2014; Oct 21. pii keu406. [Epub ahead of print]
- 8 Yee CS, Su L, Toescu V. et al. Birmingham SLE cohort: outcomes of a large inception cohort followed for up to 21 years. Rheumatology (Oxford) 2014; Oct 15. pii keu412. [Epub ahead of print]
- 9 Hawro T, Bogucki A. Krupińska-Kun M. et al Intractable Headaches, Ischemic Stroke, and Seizures Are Linked to the Presence of Anti-β2GPI Antibodies in Patients with Systemic Lupus Erythematosus. PLoS One 2015; 10 (03) e0119911. eCollection 2015
- 10 Karimifar M, Sharifi I, Shafiey K. Anti-ribosomal P antibodies related to depression in early clinical course of systemic lupus erythematosus. J Res Med Sci 2013; 18 (10) 860-864.
- 11 Mozo L, López P, Caminal-Montero L. et al Anti-ribosomal P antibodies are associated with elevated circulating IFNα and IL-10 levels in systemic lupus erythematosus patients. Lupus 2014; 23 (14) 1477-1485.
- 12 Röther E, Lang B, Coldewey R. et al Complement split product C3d as an indicator of disease activity in systemic lupus erythematosus. Clin Rheumatol 1993; 12 (01) 31-35.
- 13 Hooks JJ, Moutsopoulos HM, Geis SA. et al Immune interferon in the circulation of patients with autoimmune disease. N Engl J Med 1979; 301 (01) 5-8.
- 14 von Wussow P, Jakschies D, Hochkeppel H. et al MX homologous protein in mononuclear cells from patients with systemic lupus erythematosus. Arthritis Rheum 1989; 32 (07) 914-918.
- 15 Niewold TB. Interferon alpha as a primary pathogenic factor in human lupus. J Interferon Cytokine Res 2011; 31 (12) 887-892. Epub 2011 Sep 16
- 16 Salloum R, Niewold TB. Interferon regulatory factors in human lupus pathogenesis. Transl Res 2011; 157 (06) 326-331. Epub 2011 Feb 8
- 17 Tang JP, Gu YY, Shen N. et al [Interferon-inducible genes lymphocyte antigen 6 complex E and tetratricopeptide repeats 1 are correlated with clinical features of patients with systemic lupus erythematosus]. Zhonghua Yi Xue Za Zhi 2004; 84 (14) 1157-1160. [Chinese]
- 18 Huang J, Li RL, Zhu LN. et al [Evaluating type I interferon-inducible gene expression in patients with systemic lupus erythematosus]. Zhonghua Nei Ke Za Zhi 2010; 49 (01) 45-48. [Chinese]
- 19 Feng X, Huang J, Liu Y. et al Identification of interferon-inducible genes as diagnostic biomarker for systemic lupus erythematosus. Clin Rheumatol 2015; 34 (01) 71-79. [Epub 2014 Oct 26]
- 20 Salzer E, Santos-Valente E, Klaver S. et al B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C Δ. Blood 2013; 121 (16) 3112-3116.
- 21 Belot A, Kasher PR, Trotter EW. et al Protein kinase cΔ deficiency causes mendelian systemic lupus erythematosus with B cell-defective apoptosis and hyperproliferation. Arthritis Rheum 2013; 65 (08) 2161-2171.
- 22 Jouhadi Z, Khadir K, Ailal F. et al Ten-year follow-up of a DOCK8-deficient child with features of systemic lupus erythematosus. Pediatrics 2014; 134 (05) e1458-e1463.
- 23 Lee-Kirsch MA, Gong M, Chowdhury D. et al Mutations in the gene encoding the 3’-5’ DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet 2007; 39 (09) 1065-1067.
- 24 Oda H, Nakagawa K, Abe J. et al Aicardi-Goutières syndrome is caused by IFIH1 mutations. Am J Hum Genet 2014; 95 (01) 121-125.
- 25 Bennett L, Palucka AK, Arce E. et al Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med 2003; 197 (06) 711-723.
- 26 Nguyen C, Limaye N, Wakeland EK. Susceptibility genes in the pathogenesis of murine lupus. Arthritis Res 2002; 4 (Suppl. 03) Suppl S255-S263.