[A proposal for the MR staging of early rheumatoid arthritis in the metacarpophalangeal and proximal interphalangeal joints]. / Vorschlag einer MR-Stadieneinteilung der frühen rheumatoiden Arthritis an den Metakarpophalangeal- und proximalen Interphalangealgelenken.

PURPOSE: MRI can demonstrate pathology of joint disease in the early course of rheumatoid arthritis prior to destructions seen on conventional radiographs. In a prospective study, we tried to develop a systematical classification of joint pathology demonstrated by MRI, which would be essential for scoring the course of the disease. PATIENTS AND METHOD: Metacarpophalangeal and interphalangeal joints of 48 patients suffering from early rheumatoid arthritis (mean disease duration: 6.4 months) were evaluated by MRI using a high-resolution transmitter-receiver coil. Examinations included 2 mm sliced T2-, T1- and gadolinium enhanced T1-SE sequences in coronal and axial orientation. In consideration of pathological findings on MRI and histopathogenetical pathways of destruction in rheumatoid arthritis a MR-score (0-5) was established. RESULTS: This allowed to score each joint examined: score 0 (normal) in 47.8%/49.5%, score 1 in 35.5%/50.5%, score 2 in 4.2%/0%, score 3 in 10.8%/0%, score 4 in 1.5%/0% of the metacarpophalangeal/interphalangeal joints, respectively. CONCLUSIONS: Using the MR-score a relative individual destruction number can be calculated, which may be used to follow up patients in the early course of rheumatoid arthritis (e.g. drug therapy studies). The presented MR scoring system has to be evaluated further in longitudinal studies and must be correlated to radiographical and clinical findings.

IL-6 receptor independent stimulation of human gp130 by viral IL-6.

The genome of human herpes virus 8, which is associated with Kaposi's sarcoma, encodes proteins with similarities to cytokines and chemokines including a homologue of IL-6. Although the function of these viral proteins is unclear, they might have the potential to modulate the immune system. For viral IL-6 (vIL-6), it has been demonstrated that it stimulates IL-6-dependent cells, indicating that the IL-6R system is used. IL-6 binds to IL-6R, and the IL-6/IL-6R complex associates with gp130 which dimerizes and initiates intracellular signaling. Cells that only express gp130 but no IL-6R cannot be stimulated by IL-6 unless a soluble form of the IL-6R is present. This type of signaling has been shown for hematopoietic progenitor cells, endothelial cells, and smooth muscle cells. In this paper we show that purified recombinant vIL-6 binds to gp130 and stimulates primary human smooth muscle cells. IL-6R fails to bind vIL-6 and is not involved in its signaling. A Fc fusion protein of gp130 turned out to be a potent inhibitor of vIL-6. Our data demonstrate that vIL-6 is the first cytokine which directly binds and activates gp130. This property points to a possible role of this viral cytokine in the pathophysiology of human herpes virus 8.

Human herpes virus 8 interleukin-6 homologue triggers gp130 on neuronal and hematopoietic cells.

Human herpes virus-8 (HHV8) encodes a cytokine named viral interleukin-6 (vIL-6) that shares 25% amino-acid identity with its human homologue. Human IL-6 is known to be a growth and differentiation factor of lymphatic cells and plays a potential role in the pathophysiology of various lymphoproliferative diseases. vIL-6 is expressed in HHV8-associated-diseases including Kaposi's sarcoma, Body-cavity-based-lymphoma and Castleman's disease, suggesting a pathogenetic involvement in the malignant growth of B-cell associated diseases and other malignant tumours. We expressed vIL-6 in Escherichia coli as a fusion protein with recombinant periplasmic maltose binding protein. After cleavage from the maltose binding protein moiety and purification, vIL-6 was shown to be correctly folded using circular dichroism spectroscopy. A rabbit antiserum was raised against the recombinant vIL-6 protein. vIL-6 turned out to be active on cells that expressed gp130 but no IL-6 receptor (IL-6-R) suggesting that, in contrast to human IL-6, vIL-6 stimulated gp130 directly. Accordingly, vIL-6 activity could be inhibited by a soluble gp130 Fc Fusion protein. vIL-6 was shown to induce neuronal differentiation of rat pheochromocytoma cells and to stimulate colony formation of human hematopoietic progenitor cells. Thus, vIL-6 exhibits biologic activity that has only been observed for the IL-6/soluble IL-6-R complex but not for IL-6 alone. These properties are important for the evaluation of the pathophysiological potential of vIL-6.