502-507
Clinical rheumatology, 1992, 11, N ~ 4
Serum N Terminal Procollagen III Fragment A Predictive Marker of Joint Destruction in Rheumatoid Arthritis ? J.G.
TEBIB,
P. V I G U I E R ,
E. N O E L , F. C O L S O N , M. B O U V I E R
Y. B A R B I E R * ,
Summary
The level of the N terminal fragment of procollagen III (P3NP) levels of 100 consecutive patients affected by rheumatoid arthritis (RA) were evaluated in comparison with disease activity markers (erythrocytes sedimentation rate, C reactive protein), immunological status (rheumatoid factors, immune complexes) and joint destruction (assessed according to the Steinbrocker index). P3NP levels showed no significant relationship either to disease activity or to immunological status; however, a strong association was found between X-ray grade and P3NP values. A two-year retrospective study of 32 patients belonging to the original 100 patient population allowed us to assign a predictive value for joint destruction to the P3NP level in the early stage of the disease.
Key words
Rheumatoid Arthritis, Prognosis, Joint Destruction, Procollagen III, Disease Activity.
INTRODUCTION The disability known as rheumatoid arthritis is the result of an inflammatory process involving the synovial membrane and leads to the progressive destruction of cartilage and subchondral bone (1). Prostagladins, proteases and free radicals secreted by stimulated cells are directly responsible for the damage and for the ultimate formation of scar tissue, the mechanical properties of which impede normal function (2). This destructive process has been evaluated by radiography (3), bone scintigraphy (4) and by measurement of plasma or urinary level of "cartilage metabolism" markers and/or mediators of inflammation (5,6). Recently, attention has been drawn towards the procollagen III N terminal fragment (P3NP) levels as an inflammatory marker and its possible prognostic value (7,8). In this study the importance of this marker in the management of RA was assessed and compared with the traditional biological and radiological parameters. The lack of correlation with the acute phase reactants and the significant association with the Steinbrocker index suggest that P3NP may be a better marker of joint destruction than of inflammation. This hypothesis was Service de Rhumatologie; *Centre de Medecine Nucleaire, Centre Hospitalier Lyon Sud, 69310 Pierre Benite, France.
tested in a 2-year retrospective study and the results obtained confirm its value in assessing the early destructive stages of RA. PATIENTS AND METHODS Patients One hundred consecutive hospitalized patients (87 women and 14 men) with' a diagnosis of RA according to the 1987 ACR criteria (9) were included in the study. The patients showed no evidence of thyroid, renal or severe hepatic dysfunction at the time of the study. The average age was 59.49 years (22-87 years) and the average disease duration was 10.08 years (2 months to 66 years). All but 16 of the patients were receiving nonsteroidal anti-inflammatory drugs (NSAID) associated with a disease-modifying antirheumatic drug (DMARD : gold salt, D penicillamine, sulphasalazine methotrexate) or low dose of steroids (5 to 10 mg/day). Methods The inflammatory process was evaluated by the Westergren erythrocyte sedimentation rate (ESR) and by serum C reactive protein (CRP) level. The "immunolog-
P3NP in rheumatoid arthritis prognostic assessment
503
Table I DD DD ESR CRP EAT CIC P3NP
NS NS 0.277"* NS NS
RAD# 33.08*** 15.25"** NS NS NS 21.15"**
ESR CRP 0.616"** 0.289"** 0.484"** 0.223"
LAT NS 0.378"** NS
CIC 0.657"** NS
NS
Correlations were performed on the entire population (n :100) between disease duration (DD), radiological staging (RAD), seromarkers of disease activity (erythrocyte sedimentation rate (ESR), C reactive protein (CRP), immunological status (latex nephelometric (EAT), circulant immune complexes (CIC) and procollagen N terminal fragment (P3NP). Regression analysis was used for the quantitative data while the Kruskall-Wallis test was performed to analyse the distribution of these different data in respect to the 4 grades of the Steinbrocker classification (#). * p
Clinical rheumatology, 1992, 11, N ~ 4
Serum N Terminal Procollagen III Fragment A Predictive Marker of Joint Destruction in Rheumatoid Arthritis ? J.G.
TEBIB,
P. V I G U I E R ,
E. N O E L , F. C O L S O N , M. B O U V I E R
Y. B A R B I E R * ,
Summary
The level of the N terminal fragment of procollagen III (P3NP) levels of 100 consecutive patients affected by rheumatoid arthritis (RA) were evaluated in comparison with disease activity markers (erythrocytes sedimentation rate, C reactive protein), immunological status (rheumatoid factors, immune complexes) and joint destruction (assessed according to the Steinbrocker index). P3NP levels showed no significant relationship either to disease activity or to immunological status; however, a strong association was found between X-ray grade and P3NP values. A two-year retrospective study of 32 patients belonging to the original 100 patient population allowed us to assign a predictive value for joint destruction to the P3NP level in the early stage of the disease.
Key words
Rheumatoid Arthritis, Prognosis, Joint Destruction, Procollagen III, Disease Activity.
INTRODUCTION The disability known as rheumatoid arthritis is the result of an inflammatory process involving the synovial membrane and leads to the progressive destruction of cartilage and subchondral bone (1). Prostagladins, proteases and free radicals secreted by stimulated cells are directly responsible for the damage and for the ultimate formation of scar tissue, the mechanical properties of which impede normal function (2). This destructive process has been evaluated by radiography (3), bone scintigraphy (4) and by measurement of plasma or urinary level of "cartilage metabolism" markers and/or mediators of inflammation (5,6). Recently, attention has been drawn towards the procollagen III N terminal fragment (P3NP) levels as an inflammatory marker and its possible prognostic value (7,8). In this study the importance of this marker in the management of RA was assessed and compared with the traditional biological and radiological parameters. The lack of correlation with the acute phase reactants and the significant association with the Steinbrocker index suggest that P3NP may be a better marker of joint destruction than of inflammation. This hypothesis was Service de Rhumatologie; *Centre de Medecine Nucleaire, Centre Hospitalier Lyon Sud, 69310 Pierre Benite, France.
tested in a 2-year retrospective study and the results obtained confirm its value in assessing the early destructive stages of RA. PATIENTS AND METHODS Patients One hundred consecutive hospitalized patients (87 women and 14 men) with' a diagnosis of RA according to the 1987 ACR criteria (9) were included in the study. The patients showed no evidence of thyroid, renal or severe hepatic dysfunction at the time of the study. The average age was 59.49 years (22-87 years) and the average disease duration was 10.08 years (2 months to 66 years). All but 16 of the patients were receiving nonsteroidal anti-inflammatory drugs (NSAID) associated with a disease-modifying antirheumatic drug (DMARD : gold salt, D penicillamine, sulphasalazine methotrexate) or low dose of steroids (5 to 10 mg/day). Methods The inflammatory process was evaluated by the Westergren erythrocyte sedimentation rate (ESR) and by serum C reactive protein (CRP) level. The "immunolog-
P3NP in rheumatoid arthritis prognostic assessment
503
Table I DD DD ESR CRP EAT CIC P3NP
NS NS 0.277"* NS NS
RAD# 33.08*** 15.25"** NS NS NS 21.15"**
ESR CRP 0.616"** 0.289"** 0.484"** 0.223"
LAT NS 0.378"** NS
CIC 0.657"** NS
NS
Correlations were performed on the entire population (n :100) between disease duration (DD), radiological staging (RAD), seromarkers of disease activity (erythrocyte sedimentation rate (ESR), C reactive protein (CRP), immunological status (latex nephelometric (EAT), circulant immune complexes (CIC) and procollagen N terminal fragment (P3NP). Regression analysis was used for the quantitative data while the Kruskall-Wallis test was performed to analyse the distribution of these different data in respect to the 4 grades of the Steinbrocker classification (#). * p
