Objective To evaluate the ability of tocilizumab (a humanised anti-IL-6 receptor antibody) monotherapy to inhibit progression of structural joint damage in patients with RA. Methods In a multi-centre, x ray reader-blinded, randomised, controlled trial, 306 patients with active RA of Results Patients had a mean disease duration of 2.3 years and a disease activity score in 28 joints of 6.5 at baseline. Mean total modified Sharp score (TSS) was 29.4, which was very high despite the relatively short disease duration. At week 52, the tocilizumab group showed statistically significantly less radiographic change in TSS (mean 2.3; 95% CI 1.5 to 3.2) than the DMARD group (mean 6.1; 95% CI 4.2 to 8.0; p Conclusion Tocilizumab monotherapy was generally well tolerated and provided radiographic benefit in patients with RA.

https://ard.bmj.com/content/annrheumdis/66/9/1162.full.pdf

Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab

Copper complexes of non-steroidal anti-inflammatory drugs: an opportunity yet to be realized

Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1 (AP-1) and nuclear factor kappa B (NF-κB) transcription factors down-regulates matrix metalloproteinase gene expression in articular chondrocytes

1. YKL-40 In a search of new bone proteins, the glycoprotein YKL-40 was identified in 1989 to be secreted in vitro in large amount by the human osteosarcoma cell line MG63. The protein was named YKL-40 based on its three N-terminal aminoacids Tyrosine (Y), Lysine (K) and Leucine (L) and its molecular mass of 40 kDa (Johansen et al. 1992). This protein was later found to be similar to a protein secreted by differentiated smooth muscle cells from swine explants of the thoracic aorta (Millis et al. 1985), to a protein isolated from the whey protein secretions of bovine mammary secretions during the nonlactating period (Rejman et al. 1988), and to a heparin binding protein secreted by human synovial cells (Nyirkos et al. 1990). In the last few years there has been a growing number of publications concerning YKL-40 and the “Story about YKL-40” has probably just started. The protein has several names: “YKL-40” (Johansen et al. 1992), “Human Cartilage glycoprotein-39 (HC gp39)” (Hakala et al. 1993), “Breast regressing protein 39 Kd (brp-39)” (Morrison et al. 1994), “38-kDa heparin-binding glycoprotein (gp38k)” (Shackelton et al. 1995), “Chitinase-3-like-1 (CHI3L1)” (Rehli et al. 1997), “Chondrex” (Harvey et al. 1998), and “40 kDa mammary gland protein (MGP-40)” (Mohanty et al. 2003). Hopefully, there will in the future be consensus of its name. In this thesis the protein is named YKL-40.

Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer

Objective: To determine matrix metalloproteinase-3 (MMP-3) serum levels in patients with rheumatic diseases and to study the relation between MMP-3 and C reactive protein (CRP) levels. 

Methods: MMP-3 serum levels were determined by enzyme linked immunosorbent assay (ELISA) in (a) patients with active inflammatory rheumatic diseases: rheumatoid arthritis (RA), psoriatic arthritis, polymyalgia rheumatica, acute crystal arthritis, and ankylosing spondylitis; (b) patients with active inflammatory systemic diseases: cutaneo-articular or renal systemic lupus erythematosus (SLE), systemic sclerosis, and vasculitides; (c) patients with non-inflammatory rheumatic diseases: osteoarthritis and fibromyalgia; (d) critically ill patients without rheumatic diseases, representing an acute inflammatory control group; (e) healthy controls. 

Results: MMP-3 serum levels were significantly increased in patients with active RA, psoriatic arthritis, and polymyalgia rheumatica, whether treated or not by corticosteroids, and in female patients with acute crystal arthritis. MMP-3 serum levels were normal in steroid-free patients with active cutaneo-articular or renal SLE, systemic sclerosis, and vasculitides but were significantly increased in steroid treated patients. MMP-3 levels were normal in fibromyalgia, osteoarthritis, ankylosing spondylitis, and acute inflammatory controls. MMP-3 was significantly correlated with CRP in RA (r=0.5, p=0.0004) but not in any of the other disease groups. 

Conclusions: MMP-3 serum levels are increased in inflammatory rheumatic diseases characterised by joint synovitis, such as RA, polymyalgia rheumatica, psoriatic arthritis, and acute crystal arthritis—that is, whether the diseases are acute or chronic, erosive or not. They are normal in SLE, systemic sclerosis, and vasculitides as well as in non-rheumatic inflammatory controls, but are significantly increased by steroids. These data strongly suggest that serum MMP-3 reflects synovial inflammation.

https://ard.bmj.com/content/annrheumdis/61/2/161.full.pdf

Increased matrix metalloproteinase-3 serum levels in rheumatic diseases: relationship with synovitis and steroid treatment

Objective

To evaluate whether matrix metalloproteinase 3 (MMP-3), a proteinase that is expressed in rheumatoid synovial tissue and shows potent activity in degrading the proteoglycan of cartilage, plays a pivotal role in the joint destruction seen in early rheumatoid arthritis (RA).



Methods

In a prospective study of patients with early RA, the relationship between the serum concentration of MMP-3, as determined by a sandwich enzyme immunoassay system, and the progression of joint destruction in patients with early RA, as measured by the Larsen radiologic score, was investigated.



Results

Serum MMP-3 levels were elevated in the RA patients compared with healthy controls, not only in the late stage, but also in the early stage of the disease in patients whose duration of RA was <4 months. The serum MMP-3 level at entry into the study had a strong correlation with the Larsen score at 6 months and 12 months after entry (r = 0.58 and r = 0.49, respectively). Similarly, the serum MMP-3 level at 12 months and 24 months after entry showed a positive association with the Larsen score in the subsequent 6–12 months. Suppression of the serum MMP-3 level in the first year led to a decline in joint damage in the second year.



Conclusion

The serum concentration of MMP-3 is a useful marker for predicting bone damage in the early stage of RA, and the suppression of MMP-3 production may be an effective therapeutic approach for patients with early RA.

Serum matrix metalloproteinase 3 as a predictor of the degree of joint destruction during the six months after measurement, in patients with early rheumatoid arthritis.

We report a patient with systemic lupus erythematosus (SLE) complicated with nocardiosis. This case is very important that the complication of nocardiosis in SLE is very rare and the treatment to both SLE and nocardiosis is very difficult. A twenty-one-year old female was admitted to our hospital because of thoracic empyema and active lupus nephritis. Her medical history revealed that the diagnose of SLE was made when she was 18 with lymphocytopenia, proteinuria, positive antinuclear antibodies, and high titer of antibodies to native DNA. She was treated with prednisolne 60 mg daily and became better. Proteinuria appeared again in September 1995 and she was admitted to the former hospital. Renal biopsy proved diffuse proliferative glomeluronephritis (WHO IVb). She was treated with 1 g per day of methylprednisolone for 3 days and succeeded with 60 mg day of prednisolone. In early November she developed left chest pain and fever and chest X-ray demonstrated left pleural effusion. Antibiotics, antituberculosis, and antifungal therapy failed to subside her pleuritis and it turned to empyema. Then she was transferred to our hospital for further treatment. Nocardia farcinica was detected from the aspirated pleural fluid obtained at the former hospital. Drainage and intrathoracic impenem injection were effective. While long usage of minocycline was continued for the nocardiosis, 500 mg of cyclophosphamide pulse therapy to lupus nephritis was administrated. Two weeks later a new pulmonary lesion with left chest pain and liver abscess developed. Administration of trimethoprim-sulfamethoxazole subsided the nocardiosis. She was discharged with 1 g per day of proteinuria the prescribed 13 mg per day of prednisolone and continuous TMP-SMZ intake for nocardial infection. When immunosuppressive therapy must be given to the immunocompromised host, a more potent therapy must be added to avoid infection.

https://www.jstage.jst.go.jp/article/kansenshogakuzasshi1970/73/5/73_5_477/_pdf

Michi Tanaka

Papers

Serum matrix metalloproteinase 3 as a predictor of the degree of joint destruction during the six months after measurement, in patients with early rheumatoid arthritis.

A case of systemic lupus erythematosus complicated by Nocardia farcinica