Abstract
ObjectivesTraditionally, differences in absolute numbers of cells expressing a certain marker (e.g., positive staining cells per mm2) have been used in immunohistological synovial tissue classification. We have begun to evaluate the relative composition of the inflammatory infiltrates, i.e. percentages of inflammatory cell types in inflammatory infiltrates, as an alternate classification tool that may potentially improve tissue diagnostics, subgrouping in clinical trials, and understanding of pathogenesis of inflammatory and noninflammatory arthropathies.MethodsSynovial tissue specimens (normal synovium, n=15; orthopedic arthropathies, n=6; osteoarthritis, n=26; early undifferentiated arthritis, n=10; rheumatoid arthritis, n=26; chronic septic arthritis, n=11) were stained for CD15, CD68, CD3, CD20, and CD38. Densities of cells expressing a given marker were determined in the superficial subintima. Binary and multicategory receiver operating characteristic (ROC) analysis and naïve Bayes classifier were used to compare the abilities of (1) the absolute densities of cells expressing a given marker (absolute method) with (2) the percentages of these cells in the inflammatory cell population (relative method) to differentiate among the six tissue classes.ResultsThe inflammatory infiltrates in normal synovium and the orthopedic arthropathies consisted almost exclusively of CD68+ and CD3+ cells. Notable fractions of CD20+ and CD38+ cells appeared in a subset of osteoarthritis samples, and increased further in early, rheumatoid and chronic septic arthritis. ROC analyses and naïve Bayes classifier ranked the absolute method above the relative method in terms of overall discriminatory ability. The relative method became slightly superior when the samples were also stratified according to the total number of inflammatory cells/mm2.ConclusionsThis exploratory investigation featuring a variety of joint disorders revealed that measuring the relative proportions of inflammatory cell types may aid in synovial tissue classification if the samples are also stratified according to the intensity of inflammation.
Highlights
The absolute densities of specific inflammatory cell types have been used to classify synovial tissue samples for diagnostic or prognostic purposes, or to measure the response to therapeutic interventions (e.g., [1,2,3,4,5,6,7,8])
We find that the discriminatory accuracy of the traditional, absolute method is superior to that of the relative method for most diagnostic comparisons, but that the relative method leads to some improvement in discriminatory power when the samples are concurrently stratified according to the overall degree of inflammatory infiltration
The pathological synovial tissue samples consisted of closed needle biopsies and surgical specimens from patients with chronic septic arthritis (SeA, n=11), rheumatoid arthritis with active disease diagnosed according to the 1987 revised criteria for the classification of rheumatoid arthritis (RA, n=25), early undifferentiated arthritis (EA, n=10), osteoarthritis (OA, n=26), and “noninflammatory” orthopedic arthropathies (Orth.A, n=6)
Summary
The absolute densities (e.g., cells/mm of subintimal tissue) of specific inflammatory cell types have been used to classify synovial tissue samples for diagnostic or prognostic purposes, or to measure the response to therapeutic interventions (e.g., [1,2,3,4,5,6,7,8]) While this approach has proved useful in various scenarios, it is conceivable that a look at qualitative features of inflammatory cell populations might provide additional information in specific circumstances. A semi-quantitative scoring method yielding a score from 0 to 4, based on the estimated intensity of infiltration with individual inflammatory cell types, has been published widely and validated by an OMERACT investigator group [9] This method was shown to correlate strongly with absolute quantification obtained with digital analysis. We find that the discriminatory accuracy of the traditional, absolute method is superior to that of the relative method for most diagnostic comparisons, but that the relative method leads to some improvement in discriminatory power when the samples are concurrently stratified according to the overall degree of inflammatory infiltration
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