Several studies shows that high serum COMP is associated to more erosive disease [32,34,38,39,41,45-47] as judged by x-ray or MRI and have been used to verify progression. Sometimes but not always a significant but low association to systemic inflammation could be shown indicating that serum COMP does not directly reflect the inflammatory process like CRP and ESR but another aspect of the disease process.

Serum COMP thus reflects the ongoing process in cartilage and is widely accepted as a marker of cartilage turnover. Serum COMP has also been used in trials [35-37,42,43] to identify responders for anti-TNF treatments and monitoring treatment effect. The serum COMP levels decrease at steroid treatment and in one study patients with low serum COMP levels [35] were shown to be high responders to anti-TNF treatment.

In conclusion serum COMP in Rheumatoid Arthritis is a disease activity marker reflecting cyclic cartilage destructive periods and is not a diagnostic marker like anti-CCP and Rheumatoid factor. Consequently, serum COMP can't be used to identify a more severe disease period in such a complex and cyclic disease as Rheumatoid arthritis.

There are studies [52,53] showing that an increased COMP level in patients with psoriatic arthritis decreases upon treatment with anti-TNF agents.

In 2006 Urikami et al published a study [51] where they showed that children with systemic juvenile idiopathic arthritis had decreased serum COMP levels compared to healthy controls. They suggest that serum COMP could be used in children as a biomarker indicating growth impairment based on the fact that serum COMP reflects cartilage turnover. During the last two years these results have been verified in publications from three non-related research groups [48-50]. In these studies it was furthermore shown that the serum COMP levels were positively correlated to growth velocity, increased in the remission phase after treatment, and finally were lower in patients with joint space narrowing and joint erosions.

Reviews

1. Tseng S, Reddi AH, Di Cesare PE: Cartilage Oligomeric Matrix Protein (COMP): A Biomarker of Arthritis.
   Biomark Insights 2009, 4:33-44. PubMed Abstract | Full text
   
   
2. Williams FM, Spector TD: Biomarkers in osteoarthritis.
   Arthritis Res Ther 2008, 10:101. PubMed Abstract | Full text
   
   
3. Morozzi G, Fabbroni M, Bellisai F, Pucci G, Galeazzi M. Ann: Cartilage oligomeric matrix protein level in rheumatic diseases: potential use as a marker for measuring articular cartilage damage and/or the therapeutic efficacy of treatments.
   N Y Acad Sci 2007, 1108:398-407. PubMed Abstract
   
   
   Knee Osteoarthritis
   
   
4. Sowers MF, Karvonen-Gutierrez CA, Yosef M, Jannausch M, Jiang Y, Garnero P, Jacobson J: Longitudinal changes of serum COMP and urinary CTX-II predict X-ray defined knee osteoarthritis severity and stiffness in women.
   Osteoarthritis Cartilage 2009 Jun 21. [Epub ahead of print] PubMed Abstract
   
   
5.  Mündermann A, King KB, Smith RL, Andriacchi TP: Change in serum COMP concentration due to ambulatory load is not related to knee OA Status.
   J Orthop Res 2009 May 6. [Epub ahead of print] PubMed Abstract
   
   
6. Chua SD Jr, Messier SP, Legault C, Lenz ME, Thonar EJ, Loeser RF: Effect of an exercise and dietary intervention on serum biomarkers in overweight and obese adults with osteoarthritis of the knee.
   Osteoarthritis Cartilage 2008, 16:1047-53. PubMed Abstract | Full text
   
   
7.  Valdes AM, Loughlin J, Oene MV, Chapman K, Surdulescu GL, Doherty M, Spector TD: Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee.
   Arthritis Rheum 2007, 56:137-46. PubMed Abstract
   
   
8. Hunter DJ, Li J, LaValley M, Bauer DC, Nevitt M, DeGroot J, Poole R, Eyre D, Guermazi A, Gale D, Felson DT. Cartilage markers and their association with cartilage loss on magnetic resonance imaging in knee osteoarthritis: the Boston Osteoarthritis Knee Study.
   Arthritis Res Ther 2007, 9:R108. PubMed Abstract | Full text
   
   
9. Fernandes FA, Pucinelli ML, da Silva NP, Feldman D: Serum cartilage oligomeric matrix protein (COMP) levels in knee osteoarthritis ina Brazilian population: clinical and radiological correlation.
   Scand J Rheumatol 2007, 36:211-5. PubMed Abstract
   
   
10. Sharif M, Granell R, Johansen J, Clarke S, Elson C, Kirwan JR. Serum cartilage oligomeric matrix protein and other biomarker profiles in tibiofemoral and patellofemoral osteoarthritis of the knee.
    Rheumatology 2006, 45:522-6. PubMed Abstract | Full text
    
    
11. Jung YO, Do JH, Kang HJ, Yoo SA, Yoon CH, Kim HA, Cho CS, Kim WU. Correlation of sonographic severity with biochemical markers of synovium and cartilage in knee osteoarthritis patients.
    Clin Exp Rheumatol 2006, 24:253-9. PubMed Abstract
    
    
12. Andersson ML, Thorstensson CA, Roos EM, Petersson IF, Heinegård D, Saxne T. Serum levels of cartilage oligomeric matrix protein (COMP) increase temporarilyafter physical exercise in patients with knee osteoarthritis.
    BMC Musculoskelet Disord 2006, 7;7:98. PubMed Abstract | Full text
    
    
13. Sharif M, Kirwan JR, Elson CJ, Granell R, Clarke S: Suggestion of nonlinear or phasic progression of knee osteoarthritis based on measurements of serum cartilage oligomeric matrix protein levels over five years.
    Arthritis Rheum 2004, 50:2479-88. PubMed Abstract | Full text
    
    
14. Jordan JM, Luta G, Stabler T, Renner JB, Dragomir AD, Vilim V, Hochberg MC, Helmick CG, Kraus VB: Ethnic and sex differences in serum levels of cartilage oligomeric matrix protein: the Johnston County Osteoarthritis Project.
    Arthritis Rheum 2003, 48:675-81. PubMed Abstract | Full text
    
    
15.  Vilím V, Olejárová M, Machácek S, Gatterová J, Kraus VB, Pavelka K: Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis.
    Osteoarthritis Cartilage 2002, 10:707-13. PubMed Abstract
    
    
16. Vilím V, Vytásek R, Olejárová M, Machácek S, Gatterová J, Procházka B, Kraus VB, Pavelka K: Serum cartilage oligomeric matrix protein reflects the presence of clinically diagnosed synovitis in patients with knee osteoarthritis.
    Osteoarthritis Cartilage 2001, 9:612-8. PubMed Abstract
    
    
17.  Petersson IF, Boegård T, Svensson B, Heinegård D, Saxne T: Changes in cartilage and bone metabolism identified by serum markers in early osteoarthritis of the knee joint.
    Br J Rheumatol 1998, 37:46-50. PubMed Abstract | Full text
    
    
18.  Petersson IF, Sandqvist L, Svensson B, Saxne T: Cartilage markers in synovial fluid in symptomatic knee osteoarthritis.
    Ann Rheum Dis 1997, 56:64-7. PubMed Abstract | Full text
    
    
19.  Sharif M, Saxne T, Shepstone L, Kirwan JR, Elson CJ, Heinegård D, Dieppe PA: Relationship between serum cartilage oligomeric matrix protein levels and disease progression in osteoarthritis of the knee joint.
    Br J Rheumatol 1995, 34:306-10. PubMed Abstract
    
    
    Hand osteoarthritis
    
    
20.  Chen HC, Shah S, Stabler TV, Li YJ, Kraus VB: Biomarkers associated with clinical phenotypes of hand osteoarthritis in a large multigenerational family: the CARRIAGE family study.
    Osteoarthritis Cartilage 2008, 16:1054-9. PubMed Abstract
    
    
    Hip osteoarthritis
    
    
21. de Jong Z, Munneke M, Vilim V, Zwinderman AH, Kroon HM, Ronday HK, Lems WF, Dijkmans BA, Breedveld FC, Vliet Vlieland TP, Hazes JM, Degroot J: Value of serum cartilage oligomeric matrix protein as a prognostic marker of large-joint damage in rheumatoid arthritis--data from the RAPIT study.
    Rheumatology 2008 Jun, 47:868-71. PubMed Abstract
    
    
22. Chaganti RK, Kelman A, Lui L, Yao W, Javaid MK, Bauer D, Nevitt M, Lane NE, Study Of Osteoporotic Fractures Research Group Sof: Change in serum measurements of cartilage oligomeric matrix protein and association with the development and worsening of radiographic hip osteoarthritis.
    Osteoarthritis Cartilage 2008, 16:566-71. PubMed Abstract | Full text
    
    
23. Kelman A, Lui L, Yao W, Krumme A, Nevitt M, Lane NE: Association of higher levels of serum cartilage oligomeric matrix protein and N-telopeptide crosslinks with the development of radiographic hip osteoarthritis in elderly women.
    Arthritis Rheum 2006, 54:236-43. PubMed Abstract | Full text
    
    
24.  Kato S, Yamada H, Terada N, Masuda K, Lenz ME, Morita M, Yoshihara Y, Henmi O: Joint biomarkers in idiopathic femoral head osteonecrosis: comparison with hip osteoarthritis.
    J Rheumatol 2005, 32:1518-23. PubMed Abstract
    
    
25. Wagner S, Hofstetter W, Chiquet M, Mainil-Varlet P, Stauffer E, Ganz R, Siebenrock KA: Early osteoarthritic changes of human femoral head cartilage subsequent tofemoro-acetabular impingement.
    Osteoarthritis Cartilage 2003, 11:508-18. PubMed Abstract
    
    
26. Dragomir AD, Kraus VB, Renner JB, Luta G, Clark A, Vilim V, Hochberg MC, Helmick CG, Jordan JM: Serum cartilage oligomeric matrix protein and clinical signs and symptoms of potential pre-radiographic hip and knee pathology.
    Osteoarthritis Cartilage 2002, 10:687-91. PubMed Abstract
    
    
27. Clark AG, Jordan JM, Vilim V, Renner JB, Dragomir AD, Luta G, Kraus VB: Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: the Johnston County Osteoarthritis Project.
    Arthritis Rheum 1999, 42:2356-64. PubMed Abstract | Full text
    
    
28. Conrozier T, Saxne T, Fan CS, Mathieu P, Tron AM, Heinegård D, Vignon E: Serum concentrations of cartilage oligomeric matrix protein and bone sialoprotein in hip osteoarthritis: a one year prospective study.
    Ann Rheum Dis 1998, 57:527-32. PubMed Abstract | Full text
    
    
    Osteoarthritis (General)
    
    
29. Meulenbelt I, Kloppenburg M, Kroon HM, Houwing-Duistermaat JJ, Garnero P, Hellio-Le Graverand MP, DeGroot J, Slagboom PE: Clusters of biochemical markers are associated with radiographic subtypes of osteoarthritis (OA) in subject with familial OA at multiple sites. The GARP study.
    Osteoarthritis Cartilage 2007, 15:379-85. PubMed Abstract
    
    
30. Kong SY, Stabler TV, Criscione LG, Elliott AL, Jordan JM, Kraus VB: Diurnal variation of serum and urine biomarkers in patients with radiographic knee osteoarthritis.
    Arthritis Rheum 2006, 54:2496-504. PubMed Abstract | Full text
    
    
31. Andersson ML, Petersson IF, Karlsson KE, Jonsson EN, Månsson B, Heinegård D, Saxne T: Diurnal variation in serum levels of cartilage oligomeric matrix protein in patients with knee osteoarthritis or rheumatoid arthritis.
    Ann Rheum Dis 2006, 65:1490-4. PubMed Abstract | Full text
    
    
    Rheumatoid arthritis
    
    
32.  Fujikawa K, Kawakami A, Tamai M, Uetani M, Takao S, Arima K, Iwamoto N, AramakiT, Kawashiri S, Ichinose K, Kamachi M, Nakamura H, Origuchi T, Ida H, Aoyagi K,Eguchi K: High serum cartilage oligomeric matrix protein determines the subset of patients with early-stage rheumatoid arthritis with high serum C-reactive protein, matrix metalloproteinase-3, and MRI-proven bone erosion.
    J Rheumatol 2009, 36:1126-9. PubMed Abstract
    
    
33. Nikolaisen C, Rekvig OP, Nossent HC: Diagnostic impact of contemporary biomarker assays for rheumatoid arthritis.
    Scand J Rheumatol 2007, 36:97-100. PubMed Abstract
    
    
34. Young-Min S, Cawston T, Marshall N, Coady D, Christgau S, Saxne T, Robins S,Griffiths I: Biomarkers predict radiographic progression in early rheumatoid arthritis and perform well compared with traditional markers.
    Arthritis Rheum 2007 Oct, 56:3236-47. PubMed Abstract | Full text
    
    
35.  Morozzi G, Fabbroni M, Bellisai F, Cucini S, Simpatico A, Galeazzi M: Low serum level of COMP, a cartilage turnover marker, predicts rapid and high ACR70 response to adalimumab therapy in rheumatoid arthritis.
    Clin Rheumatol 2007 Aug, 26:1335-8. PubMed Abstract
    
    
36. Skoumal M, Haberhauer G, Feyertag J, Kittl EM, Bauer K, Dunky A: Serum levels of cartilage oligomeric matrix protein (COMP): a rapid decrease in patients with active rheumatoid arthritis undergoing intravenous steroid treatment.
    Rheumatol Int 2006, 26:1001-4. PubMed Abstract
    
    
37. Weitoft T, Larsson A, Saxne T, Rönnblom L: Changes of cartilage and bone markers after intra-articular glucocorticoid treatment with and without postinjection rest in patients with rheumatoid arthritis.
    Ann Rheum Dis 2005, 64:1750-3. PubMed Abstract | Full text
    
    
38. Momohara S, Yamanaka H, Holledge MM, Mizumura T, Ikari K, Okada N, Kamatani N, Tomatsu T: Cartilage oligomeric matrix protein in serum and synovial fluid of rheumatoid arthritis: potential use as a marker for joint cartilage damage.
    Mod Rheumatol 2004, 14:356-60. PubMed Abstract
    
    
39. Lindqvist E, Eberhardt K, Bendtzen K, Heinegård D, Saxne T: Prognostic laboratory markers of joint damage in rheumatoid arthritis.
    Ann Rheum Dis 2005, 64:196-201. PubMed Abstract | Full text
    
    
40.  Wisłowska M, Jabłońska B: Serum cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and knee osteoarthritis.
    Clin Rheumatol 2005, 24:278-84. PubMed Abstract
    
    
41.  Skoumal M, Kolarz G, Klingler A: Serum levels of cartilage oligomeric matrix protein. A predicting factor and a valuable parameter for disease management in rheumatoid arthritis.
    Scand J Rheumatol 2003, 32:156-61. PubMed Abstract
    
    
42. Crnkic M, Månsson B, Larsson L, Geborek P, Heinegård D, Saxne T: Serum cartilage oligomeric matrix protein (COMP) decreases in rheumatoidarthritis patients treated with infliximab or etanercept.
    Arthritis Res Ther 2003, 5:R181-5. PubMed Abstract | Full text
    
    
43. den Broeder AA, Joosten LA, Saxne T, Heinegård D, Fenner H, Miltenburg AM, Frasa WL, van Tits LJ, Buurman WA, van Riel PL, van de Putte LB, Barrera P: Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation.
    Ann Rheum Dis 2002, 61:311-8. PubMed Abstract | Full text
    
    
44. Roux-Lombard P, Eberhardt K, Saxne T, Dayer JM, Wollheim FA: Cytokines, metalloproteinases, their inhibitors and cartilage oligomeric matrix protein: relationship to radiological progression and inflammation in early rheumatoid arthritis. A prospective 5-year study.
    Rheumatology 2001, 40:544-51. PubMed Abstract
    
    
45.  Fex E, Eberhardt K, Saxne T: Tissue-derived macromolecules and markers of inflammation in serum in early rheumatoid arthritis: relationship to development of joint destruction in hands and feet.
    Br J Rheumatol 1997, 36:1161-5. PubMed Abstract
    
    
46.  Månsson B, Geborek P, Saxne T: Cartilage and bone macromolecules in knee joint synovial fluid in rheumatoid arthritis: relation to development of knee or hip joint destruction.
    Ann Rheum Dis 1997, 56:91-6. PubMed Abstract | Full text
    
    
47.  Forslind K, Eberhardt K, Jonsson A, Saxne T: Increased serum concentrations of cartilage oligomeric matrix protein. A prognostic marker in early rheumatoid arthritis.
    Br J Rheumatol 1992, 31:593-8. PubMed Abstract
    
    
    Juvenile Idiopathic Arthritis
    
    
48.  Bjørnhart B, Juul A, Nielsen S, Zak M, Svenningsen P, Müller K: Cartilage oligomeric matrix protein in patients with juvenile idiopathic arthritis: relation to growth and disease activity.
    J Rheumatol 2009, 36:1749-54. PubMed Abstract
    
    
49.  Nakajima S, Naruto T, Miyamae T, Imagawa T, Mori M, Nishimaki S, Yokota S: Improvement of reduced serum cartilage oligomeric matrix protein levels in systemic juvenile idiopathic arthritis patients treated with theanti-interleukin-6 receptor monoclonal antibody tocilizumab.
    Mod Rheumatol 2009, 19:42-6. PubMed Abstract
    
    
50. Gilliam BE, Chauhan AK, Low JM, Moore TL: Measurement of biomarkers in juvenile idiopathic arthritis patients and their significant association with disease severity: a comparative study.
    Clin Exp Rheumatol 2008, 26:492-7. PubMed Abstract
    
    
51. Urakami T, Manki A, Inoue T, Oda M, Tanaka H, Morishima T: Clinical significance of decreased serum concentration of cartilage oligomeric matrix protein in systemic juvenile idiopathic arthritis.
    J Rheumatol 2006, 33:996-1000. PubMed Abstract
    
    
    Psoriatic arthritis
    
    
52.  Skoumal M, Haberhauer G, Fink A, Steiner A, Klingler A, Varga F, Klaushofer K: Increased serum levels of cartilage oligomeric matrix protein in patients withpsoriasis vulgaris: a marker for unknown peripheral joint involvement?
    Clin Exp Rheumatol 2008, 26:1087-90. PubMed Abstract
    
    
53. Cauza E, Hanusch-Enserer U, Frischmuth K, Fabian B, Dunky A, Kostner K: Short-term infliximab therapy improves symptoms of psoriatic arthritis and decreases concentrations of cartilage oligomeric matrix protein.
    J Clin Pharm Ther 2006, 31:149-52. PubMed Abstract