Immunopathological mechanisms in dogs with rupture of the cranial cruciate ligament

Abstract

The majority of studies on cranial cruciate ligament (CrCL) disease to date have been carried out on dogs that already sustained a CrCL rupture, which is the end-stage of the disease. Investigations have recently been carried out to study humoral and cellular immunopathological mechanisms in predisposed dogs before clinical rupture of the contralateral CrCL. The cruciate ligaments are mainly composed of collagen type I, and immune responses to collagen have been suggested as a cause of CrCL degradation in dogs. None of these investigations showed evidence that anticollagen type I antibodies alone initiate CrCL damage. However, in predisposed dogs a distinct anticollagen type I antibody gradient was found towards the contralateral stifle joint that eventually sustained a CrCL rupture, suggesting that there was an inflammatory process present in these joints before detectable joint instability occurred. The importance of cellular reactivity to collagen type I in cruciate disease also remains unclear. Peripheral blood mononuclear cell proliferation to collagen type I was very diverse in dogs with cruciate disease whereas some sham operated dogs and healthy dogs tested positive as well. It is not yet determined whether cellular reactivity to collagen type I exists locally in the stifle joints nor whether this could initiate CrCL degradation.Inflammatory processes within the stifle joint can alter the composition of the cruciate ligaments. In animal models of immunemediated synovitis, the mechanical strength of the CrCL is significantly reduced. Immunohistochemical studies on synovial tissues from dogs with rheumatoid arthritis and dogs with cruciate disease revealed that the pathologic features are similar in both joint pathologies and that the differences are mainly quantitative. Joint inflammation induced by biochemical factors such as cytokines has been implied in CrCL degeneration. In several studies, the levels of pro-inflammatory and T helper cytokines were measured in dogs that sustained a CrCL rupture, but the exact role of the various cytokines in the pathogenesis of CrCL disease remains inconclusive. More recently, the levels of the cytokines have been investigated over time in predisposed dogs before and after CrCL rupture. IL-8 expression tended to be higher in stifle joints that will rupture their CrCL during the next 6 months than in those that will not, indicating an inflammatory process in these joints before clinical rupture.

Arthroscopic Assessment of Stifle Synovitis in Dogs with Cranial Cruciate Ligament Rupture

“…Synovial CD3 + T lymphocytes moderately correlated with the arthroscopic assessment of hypertrophy, and were typically found in aggregates or clusters. These observations reinforce the concept that there is an immune-mediated component to the CR mechanism [18] [36]. An interesting finding was that the number density of CD3 + T lymphocytes in the index and stable contralateral joints were significantly correlated, with no significant difference in T lymphocyte numbers between index and contralateral joints.…”

Radiographic Risk Factors for Contralateral Rupture in Dogs with Unilateral Cranial Cruciate Ligament Rupture

“…This finding is not surprising, since experimental induction of stifle synovitis leads to a significant reduction in cranial cruciate ligament tensile properties [30], likely because the cruciate ligament complex is supplied by fluid flow from both the ligament vascular supply as well as stifle synovial fluid [31]. These findings suggest that the immune mechanisms that lead to stifle synovitis [4], [32] should be a focus for future work. Stifle synovitis likely represents a target for disease-modifying therapy aimed at blocking disease progression.…”

“…Each year, at least one billion dollars are spent in the United States on treatment of CR and associated meniscal tearing [3]. While CR can result from trauma, a large majority of dogs develop CR during normal activity in association with pre-existing degeneration of the stifle joint and the cruciate ligament complex [4], [5]. Among dogs presented with unilateral CR, a large proportion of patients will develop contralateral CR within 12 to 24 months of initial diagnosis [6], [7].…”

Estudo biomecânico de tração (ex-vivo) em osteotomia da tuberosidade tibial de cães estabilizada com placa fixa por "garfo" ou parafuso

“…Entretanto, a maioria dos cães apresenta ruptura do LCCr em atividades normais do dia a dia, de forma secundária a degeneração progressiva e irreversível do LCCr (ARNOCZKY; MARSHALL, 1977;MOORE;READ, 1996;DOOM et al, 2008). Dessa forma a ruptura não traumática é clinicamente denominada de ruptura espontânea (DOOM et al, 2008 por Duval et al (1999).…”

“…Alterações conformacionais como a luxação medial de patela (BRINKER; PIERMATEI; FLO 1990), inclinação caudal excessiva do platô tibial (READ; ROBINS, 1982) e doença articular imunomediada, como a sinovite linfocítica plasmocítica (PEDERSEN et al, 1989;DOOM et al, 2008), podem agravar o processo degenerativo e predispor a ruptura precoce do ligamento. Entre 20 e 61% dos cães que apresentam ruptura unilateral podem sofrer ruptura do ligamento contralateral (DOVERSPIKE et al, 1993;MUELLERM, 2008;GRIERSON;ASHER;GRAINGER, 2011).…”