The Axis of Thrombospondin-1, Transforming Growth Factor Beta and Connective Tissue Growth Factor: An Emerging Therapeutic Target in Rheumatoid Arthritis

Rico, Mario C.; Rough, James J.; Carpio-Cano, Fabiola E. E. Del; Kunapuli, Satya P.; Cadena, Raul A. DeLa

doi:10.2174/1570210194858991611

Cited by 2 publications

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“…This report is the first to show that ICs in the sera of RA patients contain TSP-1, and the IC may be a promising marker for RA. Recent studies have suggested that the TSP-1/ transforming growth factor/connective tissue growth factor pathway plays an important role in angiogenesis and erosive arthritis lesions (13,14 ). Although platelet factor 4 (PF4) was less sensitive (52.4%; 95% CI, 30%-75%) than TSP-1, our method also specifically detected PF4 or a variant incorporated into CICs in RA patients for the first time (Table 1, Fig.…”

Section: Discussionmentioning

confidence: 81%

Immune Complexome Analysis of Serum and Its Application in Screening for Immune Complex Antigens in Rheumatoid Arthritis

et al. 2011

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BACKGROUND Analysis of circulating immune complexes (CICs) produced during an immune response may be useful in elucidating some aspects of this process. Identification of antigens incorporated into CICs provides information that may be helpful in developing diagnostic and treatment strategies for autoimmune diseases, infection, cancer, and transplantation therapy, and such information might be more relevant than information on free antigens. Because CICs may contain many antigens, comprehensive identification and profiling of such antigens is more effective than immunoblotting detection. METHODS We developed a novel proteomic strategy (immune complexome analysis) in which immune complexes (ICs) are separated from serum, digested directly with trypsin, and then subjected to nano-liquid chromatography–tandem mass spectrometry for identifying and profiling antigens in CICs. We applied this strategy to the analysis of CICs in 21 rheumatoid arthritis (RA) patients. Serum samples from 13 healthy donors and 8 osteoarthritis patients were used as controls. RESULTS CICs containing thrombospondin-1 (TSP-1) and platelet factor 4 (PF4) were found in the serum of 81% and 52% of RA patients, respectively, and in none of the controls. CONCLUSIONS The ICs in the serum of a majority of the RA patients contained TSP-1 or PF4, and these ICs may have potential as alternative biomarkers. Our technique for immune complexome analysis uses routine clinical samples, simple protocols, and widely available equipment. This method may be generally applicable to the study of the relationship between CICs and certain diseases associated with the immune response in animals and humans.

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Section: Discussionmentioning

confidence: 81%

Immune Complexome Analysis of Serum and Its Application in Screening for Immune Complex Antigens in Rheumatoid Arthritis

et al. 2011

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“…The TSP-1/TGF-b/CTGF axis may contribute to the pro-inflammatory and pro-atherogenic state in rheumatoid arthritis sufferers [44]. TSP-1 has also been shown to induce dendritic cell immune tolerance [45] and might therefore influence antibody formation.…”

Section: Disclosurementioning

confidence: 99%

Markers of Blood Cell Activation and Complement Activation in Factor VIII and von Willebrand Factor Concentrates

Brodde

Kehrel²

2010

Transfus Med Hemother

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SummaryBackground: Preparations of commercially available clotting factor VIII are complex protein mixtures. Most of them contain either von Willebrand factor or human serum albumin as stabilizers. The aim of the study was to quantify further proteins in twelve concentrates either of recombinant origin or derived from human plasma. Methods: Proteins were separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Some proteins were quantified by ELISA. Results: Recombinant clotting factor preparations showed fewer protein spots in the 2D-PAGE, than plasma-derived preparations. Proteins identified in some of the plasma-derived concentrates included up to 90 ng/IU of the anaphylatoxin C3a, up to 40 ng/IU of the platelet a-granule protein thrombospondin-1, up to 0.85 ng/IU of the platelet agranule protein platelet factor 4, 3.5 ng/IU myeloperoxidase secreted by leukocytes and up to 0.05 ng/IU of the leukocyte-secreted protein a-defensin. The protein content differed between concentrates from different manufacturers. Conclusion: The origin of the plasma used to prepare the factor concentrates might influence the protein impurities in these products. It is unknown whether the impurities observed have long-term consequences for chronic inflammatory conditions. Schlüsselwörter

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The Axis of Thrombospondin-1, Transforming Growth Factor Beta and Connective Tissue Growth Factor: An Emerging Therapeutic Target in Rheumatoid Arthritis

Cited by 2 publications

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Immune Complexome Analysis of Serum and Its Application in Screening for Immune Complex Antigens in Rheumatoid Arthritis

Immune Complexome Analysis of Serum and Its Application in Screening for Immune Complex Antigens in Rheumatoid Arthritis

Markers of Blood Cell Activation and Complement Activation in Factor VIII and von Willebrand Factor Concentrates

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