Urinary type II collagen neoepitope as an outcome measure for relapsing polychondritis.

Herein we describe the case of a man who was diagnosed as having relapsing polychondritis (RP) when he was 18 years of age and was treated over the course of 2 years with numerous immunosuppressive agents, including tumor necrosis factor alpha (TNFalpha) inhibitors. His respiratory symptoms were refractory to treatment. Serum and urine samples were obtained periodically for measurement of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, anti-type II collagen (anti-CII) antibodies, and urinary type II collagen neoepitope (uTIINE) levels. The uTIINE assay is specific for collagenase cleavage products CII present in urine. ESRs and CRP levels varied widely but were rarely normal. Anti-CII antibody titers were high initially and decreased slowly and steadily for a year following the start of immunosuppressive medication, remaining low throughout the remainder of the patient's monitored disease course. The uTIINE levels were elevated prior to the initiation of TNFalpha inhibitors. Upon initiation of etanercept, they decreased abruptly to normal and stayed nearly normal. The uTIINE levels rose abruptly again upon discontinuation of TNFalpha inhibitor treatment. The dramatic decline in CII degradation, coincident with the administration of the TNFalpha inhibitors, suggested that this treatment dramatically reduced the chondritis. Serum levels of Th1 cytokines (interferon-gamma, interleukin-12 [IL-12], and IL-2) paralleled changes in uTIINE levels, while those of Th2 cytokines (IL-4, IL-5, IL-6, and IL-10) showed little or no association with disease state or uTIINE levels. These results indicate that RP might be a Th1-mediated disease process. Moreover, the uTIINE assay appears to provide an objective measure of the severity of chondritis that could assist clinical decisions regarding adjustments of steroid and other immunosuppressive therapy. This outcome measure merits investigation in a broader spectrum of RP patients.

Composition of urinary glycosaminoglycans in a patient with relapsing polychondritis.

OBJECTIVES: Several investigators have reported an increase in urinary glycosaminoglycans (GAGs) in patients with relapsing polychondritis (RP). The aim of this investigation is to analyze the composition and structure of urinary GAGs from a Brazilian patient with RP. DESIGN AND METHODS: The identification and structural analyses of the GAGs were made by electrophoresis and degradation with specific enzymes and identification of their disaccharides products by HPLC chromatography. RESULTS: The disaccharide products formed from RP urinary chondroitin sulfate (CS) by action of chondroitin ABC lyase showed a substantial relative increase of nonsulfated disaccharides with a relative decrease of 6-sulfated disaccharides compared to control subjects. In addition, a significant change of the ratio of CS and heparan sulfate was also observed in the RP patient. CONCLUSION: The RP patient analyzed has shown a structural anomaly of the urinary CS and this may contribute to the diagnosis of this disease.

Analysis of increased urinary acid glycosaminoglycans in a patient with relapsing polychondritis.

We analysed the composition of glycosaminoglycans (GAGs) found in an increased amount in the urine from a patient with relapsing polychondritis (RP) by means of electrophoresis, since to our knowledge no analytical studies on the composition of GAGs in the urine from the patients with RP have been performed. Unexpectedly, the major GAGs detected in increased amount in the urine were found to be dermatan sulfate (DS) and hyaluronic acid (HA), the excretion of which correlated with the activity of the disease. Both DS and HA are the major components not of the cartilage but of the skin. Therefore, our findings suggest that the increased GAGs in RP are derived from skin or other tissues containing these GAGs rather than from the cartilage, unless there is an extensive cartilage destruction.