A Study of Some Acute Phase Reactants

Transcription

1 A Study of Soe Acute Phase Reactants in Rheuatic Diseases By BARRY DECKER, WARREN F. MCGUCKIN, BERNARD F. MCKENZIE CHARLES H. SLOCUMB AND Representative acute phase reactants and a clinical index of synovial inflaation were deterined in patients with various rheuatic diseases. The seru hexoseprotein (PR) ratio, seru proteinbound hexose and seroucoid deterinations were consistently found a ore reliable indication of the extent of systeic inflaation than the other tests studied. Systeic inflaation, easured by acute phase reactants, paralleled the clinically deterined synovial reaction only in patients with rheuatoid arthritis. Representative reactantes de phase acute e un indice clinic de inflaation synovial esseva deterinate in patientes con vane orbos rheuatic. Le proportion de hexosa a proteina in le sero, le hexosa ligate a proteina seral, e le seroucoides se provava uniforeente plus fidel coo indices del extension de inflaation systeic que le altere paraetros studiate. Le inflaation systeic, esurate per reactantes de phase acute, esseva parallel a1 clinicaente deterinate reaction synovial solente in patientes con arthritis rheuatoide. T HE PURPOSE of this paper is to copare a nuber of acute phase reactants in the seru of 65 patients with different rheuatic diseases. The two laboratory tests ost often used to easure the activity of inflaation are the erythrocyte sedientation rate and the Creactive protein tests2 Electrophoresis of seru proteins has yielded additional easures of inflaatory activity including: (1) decrease in seru albuin, (2) increase in seru alpha2 globulin2g3 and (3) increase in the alpha1 and alpha2 seru glycopr~teins.~~~ Cheically deterined fractions of the seru glycoproteins also have been shown to vary with the degree of inflaati~n.~~ These are proteinbound hexose, hexosaine, sialic acid and seroucoid. It has been suggested that the ratio of seru proteinbound hexose to total seru protein (PR) ore reliably easures the degree of inflaation than do the other variables entioned.1 The aforeentioned diverse tests have been grouped together as acute phase reactants, since they often parallel each other in their deviation fro noral during an inflaatory reaction. Dissiilar behavior ay result fro the dependence of individual tests upon different aspects of the undefined cheistry of inflaation. METHODS Uncorrected erythrocyte sedientation rates, in illieters per hour, were deterined by the ethod of Westergren. Creactive protein was graded 0 to 4 by icroprecipitation Fro the Departent of Medicine, Medical College of Virginia, Richond, Virginia and the Mayo Clinic and Mayo Foundation, Rochester, Minnesota. Abridgent of portion of thesis subitted by Dr. Decker to the Faculty of the Graduate School of the University of Minnesota in partial fulfillent of the requirnents for the degree of Master of Science in Medicine. 40

2 50 DECKER, MCGUCKIN, MCKENZIE AND SLOCUMB with specific antiseru ( ScheifIin). Seru albuin, alpha2 globulin, and alpha1 and alpha2 glycoproteins were deterined by electrophoretic ethods previously described and expressed as G. per 100 l. and as a percentage of total seru glycoprotein, respectively. Seru proteinbound hexose, as illigras per 100 nil. of seru, and seroucoid, as illigras of glycoprotein per 100 l. of seru were deterined by a odihtion of the anthronetryptophan reaction. The seru hexoseprotein ( PR) ratio was calculated as seru proteinbound hexose ties 100, divided by seru protein, deterined by the biuret ethod. The alpha1 hexoseprotein ratio was siilarly calculated fro the electrophoretically deterined alpha1 hexose and the electrophoretically deterined alpha1 globulin. A clinical grading of synovial inflaniation was accoplished independently of the laboratory data. The clinical grading was based on the degree of synovitis and secondary fibrositis (stiffness), which were graded by the ebers of the sections of rheuatology and orthopedics. Synovitis was graded 1 through 4 on the basis of swelling and thickening. Secondary fibrositis was graded 1 through 4 on the basis of pain, duration of undisturbed sleep and ability to liber with activity. Plus and inus gradations extended the range fro 0 to 12. Synovitis and secondary fibrositis, graded as described, were averaged to calculated the clinical index of synovial inflaation. The laboratory index of inflaation was calculated for each patient as an unweighted average of the values for each of the 10 acute phase reactants studied and was thought to ore closely describe the degree of systeic inflaation than any of the individual laboratory tests. The deviation of each laboratory value fro the ean control value was noted and expressed as a percentage of the axial deviation noted for that reactant in this study. The deviation was considered 0 if an individual value did not exceed the ean control value. In this anner 10 individual values for each patient were expressed as a percentage of axiu deviation and could be averaged without weighting in favor of those values reported in large nubers or having wide ranges of variation. Standard ethods of statistical analysis were applied, The correlation coefficients for each of the 10 acute phase reactants and the clinical or laboratory indices were reported as + when exceeding the rando correlation coefficient for unrelated phenoenon by two standard deviations, ++ by three standard deviations, +++ by four standard deviations, and ++++ by five standard deviations. Nuerical values of correlation coefficients were withheld, since saller variations, occurring by chance alone, are isleading. RESULTS Table 1 records the ean results deterined fro the sera of 13 noral laboratory persons, 17 patients with osteoarthritis or trauatic arthritis ( synovitis without systeic disease), 36 patients with rheuatoid arthritis or a rheuatoid variant, and 12 patients with other systeic rheuatic diseases, including lupus erytheatosus, infectious arthritis, erythea nodosu, Reiter s syndroe and hypertrophic pulonary osteoarthropathy. In all three groups of rheuatic diseases studied, the laboratory index, clinical index and the value for each acute phase reactant deviated fro the control value (table 1 ). The deviation was inial in patients with synovitis without systeic disease, ore arked in rheuatoid arthritis, and ost arked in synovitis with systeic disease other than rheuatoid arthritis. In rheuatoid arthritis (table 1) there was a significant direct correlation between the laboratory index and the clinical index of synovial inflaation. Most of the individual acute phase reactants in patients with rheuatoid arthritis, siilarly showed a significant direct correlation with the clinical index; the exceptions were albuin, alpha2 globulin and alpha2 glycoprotein. Patients with systeic or nonsysteic rheuatic diseases, other than rheuatoid arthritis, however, failed to deonstrate significant correlations between

3 z Table 1 t CORRELATION COEFFICIENTS Chid index Lpborat.oly index iz Synovitis Synovitis Synovitis with Sovitii Synovitis with 5 without 8yn. with syst. dis. without sjrstefc dia. without systeic dia. * systeic systeic systeic Control disease RA Non RA diaesse RA Nan RA disease RA NonRA 3 Nuber ESR (./hr.) CRP Proteinbound Hexose (g.jl00 l. ) Seroucoid (g. 3 protein!100 l.) CI PR Ratio i t + U+ al PR Ratio Albuin (G./100 l.) a2 Globulin (G./100 l.) i a1 Glycoprotein (%) Glycoprotein (70) Clinical Index Laboratory Index : 2 E : E

4 S2 DECKER, h1c GUCKIN, MC KENZIE AND SL0CUM.B ost individual laboratory deterinations or the average laboratory index and the clinical index of synovial inflaation. In all of the rheuatic patients, however, regardless of diagnostic category, the correlation between individual laboratory deterinations and average laboratory index was found to be excellent (table l), iplying a significant ultiple correlation. The seru hexoseprotein ratio, the total seru proteinbound hexose, and the seroucoid deterinations consistently showed the ost probable correlations with the laboratory index in all three diagnostic groups. COMMENT The seru hexoseprotein ratio, the seru proteinbound hexose and seroucoid deterinations were found to be the best indices of systeic inflaation. These glycoprotein deterinations were reliable, and correlated well with an unweighted average of ultiple laboratory tests in all the rheuatic diseases studied. It was not possible to confir the previously reported superiority of the hexoseprotein (PR) ratio over the other glycoprotein easureents. It should be noted that the erythrocyte sedientation rate copared favorably with the other acute phase reactants studied and, by virtue of its siplicity, reains the ost suitable routine index of systeic inflaation. The clinical estiate of synovial inflaation correlated significantly with ost of the acute phase reactants and particularly well with the laboratory index in rheuatoid arthritis, biit not in the other rheuatic diseases studied. In rheuatoid arthritis the synovial coponent ay coprise the greatest part of total inflaation and, as has been previously suggested, ay closely parallel the degree of systeic inflaation.12 Consequently, the seru acute phase reactants easuring the systeic integration of, or response to, focal inflaation, correlated well with clinical estiates of synovial inflaation. In patients with other rheuatic diseases, the synovial contribution to total inflaation ay bear no necessary relationship to the degree of systeic inflaation. For exaple, in lupus erytheatosus the systeic response usually exceeds the synovial anifestations while the systeic response in trauatic arthritis and degenerative joint disease is far less than the degree of synovial inflaation. The construction of this study necessitated observations at a single point of tie, during the course of a chronic disease, and consequently did not perit an evaluation of teporal variations in the acute phase reactants studied. SUMMARY 1. Changes in seru glycoproteins were consistently found a ore reliable indication of the extent of systeic inflaation than the other acute phase reactants studied. 2. The seru hexoseprotein (PR) ratio, the total seru proteinbound hexose and the seroucoid deterinations showed coparably probable correlations with an unweighted average of ultiple laboratory exainations. 3. The extent of systeic inflaation, as indicated by acute phase reactants, paralleled the extent of synovial reaction, estiated clinically, in patients with rheuatoid arthritis, but not in patients with the other rheuatic diseases studied.

5 ACUTE PHASE REACTANTS IN RHEUMATIC: DISEASES S3 REFERENCES 1. Fischel, E. E.: The erythrocyte sedien saccharide content of seru fractions tation rate and the Creactive protein in carcinoa, arthritis and infections. tests. Bull.Rheuat.Dis. 7 (suppl.): Cancer Res. 10:681683, %12, Winder, R. J.: Deterination of seru 2. Ropes, M. W., Pcrlann, G. E., Kauf glyproteins. In Click, D.: Methods an, D., and Bauer, W.: Electro of Biocheical Analysis. New York, phoretic distribution of proteins in Interscience Publishers, Inc., 1955, plasa in rheuatoid arthritis. J. vol. 2, pp ChInvest. 33:311318, Greenspan, E. M.: Survey of clinical 3. Sunderan, F. W., Jr., and Sunder significance of seru ucoprotein an, F. W.: Clinical applications of level. A.M.A.Arch.Int.Med. 93:86% the fractionation of seru proteins 874, by paper electrophoresis. A.J.Clin. 10. Stidworthy, G., Payne, R. W., Shetlar, Path. 27:125158, C. L., and Shetlar, M. R.: Objective 4. Jacqueline, F., Groulade, J., and Drufovevaluation of patients with rheuatic ka, B.: Etude quantitative, par elecdiseases. 11. Paper electrophoretic trophorese sur papier, des glucides studieb of seni glycoproteins and et des lipides cenapses aux protides protein fro patients with rheuatoid seriques dans les rhuatises chronarthritis. J.Clin.Invest. 36:30%313, iques idaatoires. Rev. du rhu :566576, Kllhns, W. J., and Cfittd, J.: Zone 11. Decker, B., McKeie, B. F., h.icguckin, electrophoresis in studies of seru W. F., and Slocub, C. H.: Coproteins, proteinbound polysacchar parative distribution of proteins and ides and seru lipids in rheuatoid glycoproteins of seru and synovial disease. J.Lab.& Clin.Med fluid. Arth. & Rheuat. 2:162177, 408, Bollet, A. J.: Hexosaine content of 13. Lansbury, J., and Free, S. M., Jr.: seru globulins. Ann.Rheuat.Dis. Quantitation of the activity of rheu 16:137, atoid arthritis. 6. Correlation of 7. Shetlar, M. R., Shetlar, C. L., Rich systeic and joint findings. A.J.M. ond, V., and Everett, M. R.: Poly Sc. 233:375378, Barry Decker, M.D., M.S., (Med.), forerly Fellow in Medicine, Mayo Foundation, University of Minnesota, Rochester, Minn.; presently Progra Director of the Arthritis Training Grant, Medical College of Virginicl, Richond, Va. Warren F. McGuckin, Ph.D., M.S. (Che.), Cotlsultant, Section of Biocheistry, Mayo Clinic; Instructor in Physiological Cheistry, Mayo Foundation, University of Minnesota, Rochester, Minn. Bernard F. McKenzie, M.S., Consultant, Section of Biocheisty,Mayo Clinic; Assistant Professor of Physiological Cheistry, Mayo Foundation, University of Minnesota, Rochester, Minn. Charles H. Slocrib, M.D., M.S. (Med.), Consultant, Section of Medicine, Mayo Clinic; Professor of Medicine, Mayo Foundution, University of Minnesota, Rochester, Minn.