Alterations of plasma glycosaminoglycan profile in patients with rheumatoid arthritis in relation to disease activity

Jura-Półtorak, Agnieszka; Komosińska-Vassev, Katarzyna; Kotulska, Anna; Kucharz, Eugene J.; Klimek, Katarzyna; Kopeć-Mędrek, Magdalena; Olczyk, Krystyna

doi:10.1016/j.cca.2014.02.027

Cited by 18 publications

(34 citation statements)

References 43 publications

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“…We are of similar opinion since we proved that treatment leading to the achievement of clinical improvement in children simultaneously contributes to normalization of this GAG concentration. It is also difficult to compare our results with those obtained in adults with rheumatoid arthritis [5]. Despite the clinical similarities between both diseases, the young age of patients with JIA could be the main factor responsible for observed changes of different GAG types in plasma.…”

Section: Discussionmentioning

confidence: 68%

“…It is known that these glycans, due to a high density of negative electric charge, interact with many types of molecules, including enzymes, growth factors, transcription factors or extracellular matrix structural proteins [3]. Although in physiological conditions GAGs are components of a dynamic structure of ECM, which is continually being remodeled, the disturbances of synthesis, modification or degradation of these polysaccharides contribute to development of connective tissue-related disorders, including rheumatoid arthritis [2,5]. Probably, these disorders are also observed in the course of juvenile idiopathic arthritis (JIA).…”

Section: Introductionmentioning

confidence: 99%

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Plasma and urinary glycosaminoglycans in the course of juvenile idiopathic arthritis

Winsz-Szczotka

Kuźnik-Trocha

Komosińska-Vassev

et al. 2015

Biochemical and Biophysical Research Communications

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Plasma and urinary glycosaminoglycans in the course of juvenile idiopathic arthritis

Winsz-Szczotka

Kuźnik-Trocha

Komosińska-Vassev

et al. 2015

Biochemical and Biophysical Research Communications

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“…Three patients suspected of an IEM had an elevation of at least one GAG in the LC-MS/MS assay and these samples were collected during periods of critical illness. An increase in GAGs during an intercurrent illness in MPS patients has been observed by our group (unpublished data) and elevated GAG levels are also described in non-MPS diseases, such as rheumathoid arthritis (RA) and septic shock [ 26 , 27 ]. With the ULN based on the 95% prediction interval, a false-positive rate of 2.5% can be expected (type I error), but we show here that testing critically ill patients might lead to more false-positive results.…”

Section: Discussionmentioning

confidence: 78%

A Multiplex Assay for the Diagnosis of Mucopolysaccharidoses and Mucolipidoses

et al. 2015

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IntroductionDiagnosis of the mucopolysaccharidoses (MPSs) generally relies on an initial analysis of total glycosaminoglycan (GAG) excretion in urine. Often the dimethylmethylene blue dye-binding (DMB) assay is used, although false-negative results have been reported. We report a multiplexed diagnostic test with a high sensitivity for all MPSs and with the potential to identify patients with I-cell disease (ML II) and mucolipidosis III (ML III).MethodsUrine samples of 100 treatment naive MPS patients were collected and analyzed by the conventional DMB assay and a multiplex assay based on enzymatic digestion of heparan sulfate (HS), dermatan sulfate (DS) and keratan sulfate (KS) followed by quantification by LC-MS/MS. Specificity was calculated by analyzing urine samples from a cohort of 39 patients suspected for an inborn error of metabolism, including MPSs.ResultsThe MPS cohort consisted of 18 MPS I, 16 MPS II, 34 MPS III, 10 MPS IVA, 3 MPS IVB, 17 MPS VI and 2 MPS VII patients. All 100 patients were identified by the LC-MS/MS assay with typical patterns of elevation of HS, DS and KS, respectively (sensitivity 100%). DMB analysis of the urine was found to be in the normal range in 10 of the 100 patients (sensitivity 90%). Three out of the 39 patients were identified as false-positive, resulting in a specificity of the LS-MS/MS assay of 92%. For the DMB this was 97%. All three patients with MLII/MLIII had elevated GAGs in the LC-MS/MS assay while the DMB test was normal in 2 of them.ConclusionThe multiplex LC-MS/MS assay provides a robust and very sensitive assay for the diagnosis of the complete spectrum of MPSs and has the potential to identify MPS related disorders such as MLII/MLIII. Its performance is superior to that of the conventional DMB assay.

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“…These levels are reported to be especially high in the synovial fluid of Lyme arthritis patients (21), consistent with a localized response. Alterations in plasma GAG profiles have also been identified in rheumatoid arthritis patients and correlated with the level of ongoing disease activity (22). …”

Section: Discussionmentioning

confidence: 99%

β-Glucuronidase, a Regulator of Lyme Arthritis Severity, Modulates Lysosomal Trafficking and MMP-9 Secretion in Response to Inflammatory Stimuli

Bramwell

Mock

et al. 2015

The Journal of Immunology

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The lysosomal enzyme beta-glucuronidase (Gusb) is a key regulator of Lyme-associated and K/B×N-induced arthritis severity. The luminal enzymes present in lysosomes provide essential catabolic functions for the homeostatic degradation of a variety of macromolecules. In addition to this essential catabolic function, lysosomes play important roles in the inflammatory response following infection. Secretory lysosomes and related vesicles can participate in the inflammatory response through fusion with the plasma membrane and release of bioactive contents into the extracellular milieu. Here we show that GUSB hypomorphism potentiates lysosomal exocytosis following inflammatory stimulation. This leads to elevated secretion of lysosomal contents, including glycosaminoglycans, lysosomal hydrolases, and Matrix Metalloproteinase 9, a known modulator of Lyme arthritis severity. This mechanistic insight led us to test the efficacy of Rapamycin, a drug known to suppress lysosomal exocytosis. Both Lyme and K/B×N-associated arthritis were suppressed by this treatment concurrent with reduced lysosomal release.

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Alterations of plasma glycosaminoglycan profile in patients with rheumatoid arthritis in relation to disease activity

Cited by 18 publications

References 43 publications

Plasma and urinary glycosaminoglycans in the course of juvenile idiopathic arthritis

Plasma and urinary glycosaminoglycans in the course of juvenile idiopathic arthritis

A Multiplex Assay for the Diagnosis of Mucopolysaccharidoses and Mucolipidoses

β-Glucuronidase, a Regulator of Lyme Arthritis Severity, Modulates Lysosomal Trafficking and MMP-9 Secretion in Response to Inflammatory Stimuli

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