Ann Rheum Dis: first published as 10.1136/ard.47.8.665 on 1 August 1988. Downloaded from Annals of the Rheumatic Diseases, 1988; 47, 665-671 Serum ac antichymotrypsin concentration as a marker of disease activity in rheumatoid arthritis M D CHARD,' J CALVIN,2 C P PRICE,2 T E CAWSTON,' AND BL HAZLEMAN' From the 'Rheumatology Research Unit and the 2Department of Clinical Biochemistry, Addenbrooke's Hospital, Hills Road, Cambridge SUMMARY Serum a1 antichymotrypsin (ctACT), C reactive protein (CRP), orosomucoid, and erythrocyte sedimentation rate (ESR) were measured sequentially in 20 patients with rheumatoid arthritis (RA) treated with gold or penicillamine. Pain score, morning stiffness, grip strength, and articular index were measured and a Mallya score calculated. Based on a total of 148 sets of observations, significant correlations were found between acACT and other variables (p<0.001 except morning stiffness at p<0O05). The actual correlation coefficients indicated a closer association with the other laboratory tests, CRP (0-62), orosomucoid (0.69), and ESR (0.61), than with clinical measurements: pain score (0.38), articular index (0-41), grip strength (-0.3), morning stiffness (0.19), and Mallya score (0.5). Sequential data on individual patients showed differing patterns of change in the variables indicating the importance of measuring more than one acute phase protein (APP), especially when CRP is inappropriately low. Serum a1ACT copyright. concentration does reflect disease activity in RA. Its potential advantages are discussed. Key words: C reactive protein, acute phase proteins. Serum acute phase proteins (APPs) rise during the Some APPs that have been used, such as fibri- course of an acute inflammatory reaction but may nogen and caeruloplasmin, usually show only a http://ard.bmj.com/ also be raised in chronic inflammatory conditions modest rise. In addition, tlhcir concentration and such as rheumatoid arthritis (RA). also those of haptoglobin, orosomucoid (at acid Measurement of these proteins in RA has been glycoprotein), and a, antitrypsin are affected by shown to be of value in assessing disease activity, the various factors not directly related to inflammation.7 response to treatment, and prognosis.'-3 The APPs More recently serum amyloid A protein (SAAP) traditionally measured would appear to have been measurement has been reported as being a useful chosen more on the availability of existing measur- APP to measure, behaving similarly to CRP but on September 25, 2021 by guest. Protected ing techniques than on theoretical grounds. with some possible advantage.9 As production is Production of APPs in the liver is thoufht to be more quickly switched on by inflammation, produc- stimulated by the cytokine interleukin 1. Despite ing a large response, small fluctuations in disease this common inducer, individual APPs do not rise in activity and other events such as minor infection parallel in some disease, indicating that secondary may give rise to difficulties in the interpretation of a control factors may be operating. In addition, some rise in concentration. patients do not respond as expected. C reactive a, Antichymotrypsin (alACT) is a serine protease protein (CRP), the most widely used APP,6 may be inhibitor which also rises in inflammatory condi- normal even though active RA is indicated on tions. Measurement of this APP has theoretical clinical grounds or by the concentration of other advantages over most others. It increases more APPs.7 It has therefore been advocated that quickly and to a greater extent than other APPs, measurement of a number of APPs may have apart from CRP or SAAP, "' but being less sensitive advantages. 8 than these two may be less altered by minor events. In addition, its concentration remains raised for a Accepted for publication 7 January 1988. long period and so a significant inflammatory Correspondence to Dr M D Chard. Rheumatology Research Unit. episode is unlikely to be missed. Concentrations are Addenbrooke's Hospital, Hills Road, Cambridge CB2 200. not affected by genetic variation, sex hormones, or 665 Ann Rheum Dis: first published as 10.1136/ard.47.8.665 on 1 August 1988. Downloaded from 666 Chard, Calvin, Price, Cawston, Hazleman corticosteroid administration, and renal function has and drug treatment were recorded. Disease activity no significant effect. "-13 Also, from a practical was assessed on each occasion clinically by the point of view, because the concentration does not following: pain score, using a 10 cm visual analogue rise as dramatically as that of CRP the assay systems scale; duration of morning stiffness; grip strength can avoid costly and time consuming dilution steps. (mean of three measurements); articular index. 14 Therefore, ocACT measurement may be a useful Blood was taken for measurement of the haemoglo- APP to measure in assessing RA. This study was bin, ESR (Westergren), CRP, orosomucoid, and undertaken to find out if the serum ot,ACT corre- auACT. CRP was measured with a Beckman rate lates with clinical and laboratory measures of nephelometer (Beckman RIIC, High Wycombe, disease activity in RA. UK). Orosomucoid and a,ACT were measured by immunoturbidimetric assays on an Instrumentation Patients and methods Laboratory multistat centrifugal analyser.'S (1 The normal range of a,ACT was determined from 128 A group of 20 outpatients (14 women, six men) with healthy blood donors (0-35-0-64 g/l). The Mallya classical or definite RA (American Rheumatism score for each patient was calculated at each visit as Association criteria) were studied. All were seen described previously.'7 initially when they had active disease while taking a Associations between the serum concentration of non-steroidal anti-inflammatory drug, and were a,ACT and the clinical and laboratory variables starting a second line agent (gold or penicillamine). were determined using the Spearman rank correla- Each was then seen on several further occasions tion test. Analysis of variance was used to check for while undergoing treatment over subsequent months any bias effect on the overall results by any when the disease activity might have been changing individual patient. in response to their treatment. They were seen on a mean of seven (range 4-14) occasions. This resulted Results in a total of 148 sets of observations. copyright. Details of age, duration of RA, seropositivity, The mean age of the patients was 51 (range 32-68) 4.0 l ~~~~~~r= 0.1.69 3.5 http://ard.bmj.com/ 3.0 - I-z: 0 2.5 z on September 25, 2021 by guest. Protected z U0 2.0 - .1 z .1 1....... 0 o 1.0 f- 0.5 a I I I I I I I I 9 -I 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6 ALPHA I ANTICHYMOTRYPSIN CONCENTRATION (g/l) Fig. 1 Correlation ofa, antichymotrypsin and orosomucoid concentration in rheumatoid arthritis. Ann Rheum Dis: first published as 10.1136/ard.47.8.665 on 1 August 1988. Downloaded from Serum cc antichymotrypsin as a disease marker in RA 667 years. Eighteen had seropositive disease and the was rarely found in the presence of either a raised mean duration of RA was five (range 0-5-12) years. CRP concentration or ESR. These findings were Table I shows the correlation coefficients for the obtained in both gold and penicillamine treated measured a,ACT concentration. There was a close patients. association between a,ACT and the other labora- The results from individual patients were shown tory variables. This occurred over values both within not to affect the overall associations, which re- and above the normal ranges as illustrated by the mained highly significant. None of the other labora- plot against orosomucoid (Fig. 1). There was overall tory parameters showed a significantly greater asso- a good correlation with CRP but a raised concentra- ciation with the clinical variables. tion of a,ACT was not infrequently found in the Although correlations with clinical variables were presence of a normal CRP (Fig. 2). A somewhat less marked, apart from the composite Mallya score, similar pattern was seen when comparing a,ACT they were significant at the level of p<0001 with the with ESR (Fig. 3). By comparison, a normal a,ACT exception of morning stiffness (p<005). A normal concentration of auACT was rarely found in the qresence of clinically active disease as shown by the Table I Correlation between ca, antichvmotrvpsin plot against the articular index (Fig. 4). (c,A CT) and other variables (n= 148) The sequential measurements on individual pa- Variable Correlationi Signzificantice (p) tients provided additional information which is coefficienit (r) illustrated by data on four selected patients (Figs 5a-d). Although there was broad agreement be- ESR 0 61 <0.((X) tween the variables in most patients as disease CRP 0(62 <0()()1 Orosomucoid 0(69 <(-N1 activity changed (Fig. 5, pattern 1), there were some Pain scorc 0(38 <(0(1 patients where there were differences. In three Ritchie articular indcx 0(41 <(0(0)1 patients atACT took longer to settle than the other Grip strcngth -0 30 <0(0)1 variables (Fig. 5, pattern 2). On seven occasions in copyright. Morning stiffncss ( 19 <0(05 Mallya score 0-50 <0(X)( six patients CRP was normal despite other evidence of active disease (Fig. 5, pattern 3). In a further = r 0.62 http://ard.bmj.com/ z YU 2 on September 25, 2021 by guest. Protected < 80 z 70 z ° 60 <, 50 40 I .*~ 30 I :> ... 20 1 .r<;~~~~~:,-f*. .~: * 10 I --*.1". " *- -_.: O.- .....tZ.- . I I 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6 ALPHA IANTICHYMOTRYPSIN CONCENTRATION (g/l) Fig.