Joerg Hoffmann

BACKGROUND: Tumor necrosis factor alpha (TNFalpha) is a proinflammatory cytokine and an important mediator in the pathophysiology of inflammatory bowel disease (IBD). The effects of TNFalpha are mediated by 2 specific receptors, a 55-kDa protein (TNF-RI) and a 75-kDa receptor (TNF-RII), which are usually bound to the cell surface. Soluble TNF receptors I and II (sTNF-RI + II) are released by proteolytic cleavage of the extracellular domains of these receptors. Soluble TNF-Rs act as TNF antagonists and can inhibit TNFalpha-mediated proinflammatory effects. METHODS: Levels of sTNF-RI + II were measured using commercially available enzyme-linked immunosorbent assays (ELISAs). Serum levels of sTNF-RI + II of 76 healthy volunteers were compared to serum levels of 373 clinically well-characterized patients with Crohn's disease (CD) and 118 patients with ulcerative colitis (UC) with different disease activity from the German IBD competence network serum bank. CD patient subgroups were defined according to the Vienna Classification. RESULTS: The serum levels of sTNF-RI were significantly increased in all groups (active, chronic active, and remission) of CD and UC patients compared to healthy controls. sTNF-RII levels were significantly higher in active CD patients compared to UC patients with no overlap of the 95% confidence interval. Significantly higher values of sTNF-RII compared to controls were also observed in CD patients and UC patients in remission. There was no statistically significant difference in sTNF-RI or sTNF-RII levels when patient subgroups were analyzed according to disease behavior or disease localization. CONCLUSION: sTNF-RI is upregulated in the serum of IBD patients compared to healthy controls and could be used as a marker for disease activity. sTNF-RII levels are significantly more elevated in serum of active CD patients as compared to UC and could be used as an additional parameter to discriminate both diseases.

Der M. Crohn ist neben der Colitis ulcerosa die wichtigste chronisch entzündliche Darmerkrankung. In der Häufigkeit des M. Crohn liegt Deutschland mit 5,2 pro 100 000 im Durchschnitt Europas, das eine jährliche Inzidenz von 5,6 pro 100 000 aufweist [1] [2]. Die Zahl der Patienten in Deutschland mit entzündlichen Darmkrankheiten wird von der Deutschen Crohn- und Colitis-Vereinigung mit ca. 320 000 angegeben. Somit dürfte die Prävalenz des M. Crohn bei etwa 1/500 bis 1/800 liegen. Der Beginn der Erkrankungssymptome liegt im Mittel bei 30 Jahren [2], d. h., die Patienten sind oft während ihrer gesamten beruflichen Laufbahn von der Erkrankung betroffen. Dementsprechend belasten sowohl die direkten medizinischen Kosten als auch die Arbeitsausfälle durch rezidivierende Schübe oder chronische Aktivität das Sozialwesen mit erheblichen Kosten. Die Gesamtkosten wurden kürzlich für Deutschland auf 20 000 Euro pro Fall und Jahr geschätzt [3], davon 69 % indirekte Kosten. Dies entspricht einem Gesamtkostenaufwand für den M. Crohn von etwa 2 Milliarden Euro, in den USA wurden die ökonomischen Gesamtkosten für beide entzündliche Darmerkrankungen auf bis zu 2,6 Milliarden Dollar geschätzt [3].

BACKGROUND: The Matutes score (MS) was proposed to differentiate chronic lymphocytic leukemia (CLL) from other B-cell non-Hodgkin lymphomas (B-NHLs). However, ambiguous immunophenotypes are common and remain a diagnostic challenge. Therefore, we evaluated the diagnostic benefit of measuring CD200 and CD43 expression together with the standard MS antigens. METHODS: 138 lymphoma patient samples and a validation cohort of 138 additive samples were classified according to the standard MS and further assigned with one or two additional points, for high CD200 and/or CD43 expression levels. The "classical" MS and the "Matutes score-extended" (MS-e) were categorized as high (4-5/6-7), intermediate (2-3/4-5), and low (0-1/0-3). Samples were reclassified into the MS-e with focus on ambiguous cases with an intermediate "classical" MS. RESULTS: A total of 35 of 138 (25.4%) patient samples were assigned to the intermediate MS group and confirmed by histopathological reports as CLL (14/40.0%) and B-NHLs other than CLL (21/60%). MS-e analysis identified 13 of 14 (92.9%) of CLL cases (MS-e 4-5) and 18/21 (85.7%) non-CLL cases (MS-e ≤ 3) correctly. Overall, the sensitivity of the CLL diagnosis was significantly increased by application of MS-e compared to the "classical" MS (98.8% vs. 82.7%; p = 0.0009), while specificity of both methods was almost equal (94.7% vs. 98.3%; p = 0.4795). Of note, sole measurement of CD43 and CD200 on B-cells sufficiently differentiated CLL from non-CLL with a test accuracy superior to the "classical" MS (F1 score 96.2 vs. 93.6). CONCLUSION: CD200 and CD43 have a high informative value in diagnostic immunophenotyping and facilitate the separation of CLL from other B-NHLs particularly in ambiguous cases.