Journal of Clinical Immunology, VoL 12, No. 5, 1992 Disease Severity in Rheumatoid Arthritis: Relationships of Plasma Tumor Necrosis Factor-s, Soluble Interleukin 2-Receptor, Soluble CD4/CD8 Ratio, Neopterin, and Fibrin D-Dimer to Traditional Severity and Functional Measures JEAN C. BECKHAM, 1 DAVID S. CALDWELL, 2 BERCEDIS L. PETERSON, 1 ANNE M. M. PIPPEN, 3 MARK S. CURRIE, 3 FRANCIS J. KEEFE, l and J. BRICE WEINBERG 3'4 Accepted: May 6, 1992 Rheumatoid arthritis is a complex inflammatory disease of unknown cause. Although various laboratory and clinical measurements are useful in managing these pa- tients, there is a need for better tests to quantitatively assess disease activity. The purpose of this study was to investigate the association of certain immune and inflam- mation (I-I) parameters with four traditional disease se- verity measures and a functional measure in rheumatoid arthritis patients. A single set of patient blood samples was analyzed, and four traditional disease severity mea- sures and patient functional statuses were determined from 64 consecutive outpatients with rheumatoid arthri- tis. Plasma tumor necrosis factor-alpha (TNF), soluble interleukin-2 receptor (sIL-2R), sCD4 and sCD8 (and the sCD4/sCD8 ratio), neopterin, and fibrin D-dimer were analyzed in relationship to Westergren erythrocyte sedi- mentation rate (ESR), physician assessment of disease activity, joint pain count, grip strength, and Arthritis Impact Measurement Scale (AIMS) scores. Rheumatoid arthritis patients had higher mean levels of all I-I mea- sures (except sCD4) compared to healthy subjects. Initial ~Division of Medical Psychology, Department of Psychiatry, Duke University and VA Medical Centers, and the Duke University Arthritis Center, Durham, North Carolina 27710. 2Division of Rheumatology and Immunology, Department of Medicine, Duke University and VA Medical Centers, and the Duke University Arthritis Center, Durham, North Carolina 27710. 3Division of Hematology and Medical Oncology, Department of Medicine, Duke University and VA Medical Centers, and the Duke University Arthritis Center, Durham, North Carolina 27710. *fo whom correspondence should be addressed at VA and Duke University Medical Centers, 151G, Durham, North Carolina 27705. 353 significant correlations between TNF, slL-2R, and D-di- mer and several disease severity and functional measures were detected. When we controlled for the covariates age, gender, race, and medications, regression analyses indicated that, as a group, the I-I measures were signifi- cantly related to grip strength, physician disease severity rating, ESR, and total joint pain. When the predictive values of the I-I measures were tested controlling for the covariates and ESR, D-dimer was independently and significantly associated with variability in grip strength, physician disease severity, and AIMS physical disability, while TNF was associated with a significant amount of variability in total joint pain. The results indicate that these immune and inflammation parameters may be sig- nificantly elevated in rheumatoid arthritis patients and that certain measures (e.g., plasma fibrin D-dimer) may be especially useful in objectively evaluating disease activity in RA patients. KEY WORDS: Rheumatoid arthritis; immunity; inflammation. INTRODUCTION Quantitative assessment of disease activity in rheu- matoid arthritis is an important, ongoing research and clinical issue (1, 2). There is no definitive laboratory test that is specific for rheumatoid arthri- tis. Nevertheless, laboratory tests can be valuable since their results, in conjunction with clinical find- ings, may contribute to differential diagnosis, en- able quantitation of disease activity, and serve as a guide in assessing the efficacy of treatments. Re- cently, various investigators have been investigat- ing a number of immune and inflammation (I-I) 0271-9142D2/0900-0353506,50/0 © I992Plenum Publishing Corporation