Distribution of T cells and signs of T-cell activation in the rheumatoid joint: implications for semiquantitative comparative histology

Abstract

A prerequisite for comparative histology of synovial tissue by means of biopsies is insight into the distribution of a marker under study. This investigation focuses on the variation in the presence of T cells and signs of T-cell activation within the rheumatoid joint. For this purpose, multiple slides from several pieces of synovial tissue from different parts of a joint were stained and scored for the expression of CD3, CD25, HLA-DR, Ki67 and interferon-gamma. The variation in scores for the presence of T cells and markers of activation was more pronounced in slides prepared from different pieces of tissue than in slides from one piece of tissue. Based on multiple analysis of variance, methods are suggested to establish a reliable overall score for the expression of a certain marker within a joint. Following validation, such methods may prove to be useful by allowing semiquantitative histology of synovial tissue for studies on arthritis.

Use of Ultrasound‐Guided Small Joint Biopsy to Evaluate the Histopathologic Response to Rheumatoid Arthritis Therapy: Recommendations for Application to Clinical Trials

“…Notably, when pathologic heterogeneity of the immune cell infiltrate in large joints is systematically examined, the variability is highest between rather than within biopsy specimens (19), an observation that is consistent with the results of the present study of small joints. These observations strongly suggest that determining the number of synovial biopsies required, rather than simply the number of tissue sections per joint (as previously reported [5]), is critical to obtaining a representative estimate of the immune cell infiltration of the whole joint.…”

“…Though 6 synovial biopsies are recommended when sampling large synovial joints in order to overcome morphologic heterogeneity for both pathobiologic (19) and gene expression analysis (20), the extrapolation of these requirements to small joints in which synovial volume is much reduced was not previously validated. Notably, when pathologic heterogeneity of the immune cell infiltrate in large joints is systematically examined, the variability is highest between rather than within biopsy specimens (19), an observation that is consistent with the results of the present study of small joints.…”

Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response

“…To minimise sampling error at least six biopsy samples were obtained from different sites in the joint during each procedure 9 10. Specimens were directly embedded en bloc in TissueTek OCT (Miles Diagnostics, Elkhart, Indiana, USA) and subsequently snap-frozen in liquid nitrogen.…”

Alefacept treatment in psoriatic arthritis: Reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis

“…To reduce sampling error, a minimum of 6 tissue specimens were processed for immunohistochemistry and for formalin fixation, each as described previously (33)(34)(35). Immunohistochemical analysis.…”