Presentation: The Synovium in Gulf War Veterans’ Illness: Quantitative Histopathologic Comparisons to OA and Normal Synovium (2007)

1542 The Synovium in Gulf War Veterans’ Illness: Quantitative Histopathologic Comparisons to OA and Normal Synovium

Background. We have previously reported the histologic absence of synovitis in synovial biopsies from 6 individuals with Gulf War Veterans Illness (GWVI) and joint pain and features of chronic fatigue and/or fibromyalgia [1].
Objective. To assess in detail histopathologic and vascular features of synovial biopsies from an expanded group of 10 patients with GWVI and joint pain, compared to normal and OA synovium.
Methods. Synovial membranes from individuals with GWVI (n=10), healthy volunteers (n=10) and patients with OA (n=18) were assessed for: Lining thickness, synovitis score [2], and vascular density in H&E stained sections; and densities of CD15 (neutrophils), CD3 (T cells), CD8 (cytotoxic T cells), CD20 (B cells), CD38 (plasma cells), CD68 (macrophages), and Ki-67 (dividing cells) expressing cells and von Willebrand Factor+ vessels by immunohistochemistry.
Results (Table). Histology was identical in the GWVI and normal specimens. Mean lining thickness was similar in all three specimen groups. Synovitis scores classified the normal and GWVI specimens as “no synovitis” and OA as “mild synovitis.” Vascular densities were identical in GWVI and normal controls, but were 35-40% higher in OA. Absolute numbers and percentages of CD68+ lining cells were equal in GWVI and normal synovia, but 2-3 times higher in OA. All GWVI and normal synovia contained similar small numbers of mononuclear inflammatory cells, consisting almost exclusively of T cells and CD68+ macrophages. Remarkably, there were practically no CD20, CD38 and CD15+ cells in the GWVI and normal specimens. While all inflammatory cell types occurred more frequently in OA, a principal difference was the presence of CD20+ and CD38+ cells in a small subset of OA specimens.
Conclusions. The synovial biopsies from these patients with chronic unexplained knee pain were histopathologically indistinguishable from biopsies obtained from healthy volunteers. Low levels of cellular immunity were detected immunohistochemically, but these were similar in magnitude to those found in normal synovium, and are unlikely related to the pain. OA synovium could be distinguished by higher numbers of the same inflammatory cells, but also by increased vascularization and the presence of humoral immunity in a small subset of specimens.
1. Diaz-Torne et al. Arthr Rheum (Arthr Care Res) in press.
2. Krenn et al. Pathol Res Pract 2002; 198:317-325.
AssessmentNormal (+/-SEM)GWVIOA
Lining thickness (cell layers)1.3 (0.05)1.4 (0.07)1.7 (0.14)
VesselsH&E51.8 (2.9)50.3 (1.7)67.3 (5.7)*
vWF64.8 (3.0)61.0 (1.9)88.6 (8.6)*
Synovitis score1.38 (0.30)1.41 (0.29)2.6 (0.39)*
LiningTotal CD68+ cells7.4 (1.9)6.8 (1.7)20.3 (2.9)*
% CD68+ cells33.3 (6.1)25.0 (1.7)60.7 (7.7)*
Subintima1Ki-67n/d7.5 (2.5)27.2 (6.9)*
CD15n/d0.6 (0.3)1.3 (0.7)
CD327.1 (9.2)15.1 (6.3)54.7 (11.1)*
CD202.3 (1.2)1.6 (1.3)11.1 (8.2)
CD38n/d0.2 (0.2)20.9 (13.3)
CD6845.6 (7.4)45.3 (10.1)166.5 (27.7)*
(1) positive staining cells per mm2. *p<0.05 vs. GWVI and normal

 F. Pessler, None; L.X. Chen, None; C. Gomez-Vaquero, None; N. Cakir, None; C. Diaz-Torne, None; E. Einhorn, None; H. Schumacher, None.