Lymphocyte Proliferation to Collagen Type I in Dogs

Abstract

Summary The objective of this study was to investigate if cellular reactivity to collagen type I exists in dogs with unilateral cranial cruciate ligament (CrCL) rupture and if it relates to disease progression. The patient group consisted of 10 dogs with unilateral CrCL rupture. The control dogs consisted of three healthy control dogs, and two healthy dogs with unilateral sham operations of the stifle joint. All dogs were assayed repeatedly every 6 months for 12–24 months. Peripheral blood mononuclear cells were isolated from whole blood and were cultured with human collagen type I at concentrations of 5, 20 and 40 μg/ml for 6 and 7 days. Lymphocyte reactivity to collagen type I occurred not only in dogs with CrCL rupture, but also in sham‐operated dogs and healthy dogs. Five of the eight assays (63%) performed at the time of operation or at the time of diagnosis of CrCL rupture had a stimulation index (SI) ≥3.0. This was not significantly different compared to healthy control dogs, not to the sham‐operated control dogs. The CrCL rupture was assessed intraoperatively in six cases. Three cases had partial rupture and three had complete rupture. Only one dog with partial rupture, and two dogs with complete rupture had a positive SI. An increase in proliferation to collagen type I was seen in dogs with CrCL rupture, whereas it either remained stable or decreased in the control dogs. No distinct pattern in lymphocyte reactivity to collagen type I could be established from the dogs that sustained a CrCL rupture in the contralateral stifle joint, although most dogs that did not sustain a CrCL rupture in the contralateral stifle joint remained negative during this study with exception of one dog. Further research is required to determine whether cellular reactivity to collagen type I may play an initiating role in cruciate degradation.

Immunopathological mechanisms in dogs with rupture of the cranial cruciate ligament

“…In a recent study lymphocyte reactivity to collagen type I was assessed in dogs with cruciate disease by culturing peripheral blood mononuclear cells with human collagen type I, and was compared to sham operated and normal dogs. This study demonstrated that lymphocyte reactivity to collagen type I does occur in dogs with CrCL rupture, however, some of the sham operated dogs and healthy dogs tested positive as well (de Bruin et al, 2007b). In addition, PBMC proliferation to collagen type I was very diverse in dogs that sustained a CrCL rupture in the contralateral stifle joint, suggesting that collagen reactive T cells do not play a primary role in CrCL disease.…”

Lymphocyte Populations in Joint Tissues from Dogs with Inflammatory Stifle Arthritis and Associated Degenerative Cranial Cruciate Ligament Rupture

“…The identity of the antigenic trigger for lymphocytic synovitis within the stifle of dogs with CCLR is unclear. Several studies have explored the hypothesis that neoepitopes of type I and type II collagen may be the immunologic trigger 6,46,47 . We have hypothesized that bacterial material may act as an antigenic trigger in this condition.…”

“…Several studies have explored the hypothesis that neoepitopes of type I and type II collagen may be the immunologic trigger. 6,46,47 We have hypothesized that bacterial material may act as an antigenic trigger in this condition. Translocation of bacterial material to the stifle joint is common in this arthropathy, 48 but further work is needed to determine whether a cause-effect relationship exists.…”

Contralateral Cruciate Survival in Dogs with Unilateral Non-Contact Cranial Cruciate Ligament Rupture

“…At the present time, there are two hypotheses regarding the mechanism that leads to development of inflammatory stifle arthritis and eventual CrCLR: (1) cruciate fiber rupture is a consequence of a primary synovitis [8], and (2) intrinsic and extrinsic factors induce fiber rupture, with subsequent induction of synovitis by ligament matrix neoepitopes [19]–[21]. The immunologic trigger for synovitis for the first hypothesis is not known, although the presence of bacterial material within the stifle has been associated with the condition [22]–[24].…”