Pathogenesis and immunopathology of systemic and nervous canine distemper

Canine distemper is a worldwide occurring infectious disease of dogs, caused by a morbillivirus, closely related to measles and rinderpest virus. The natural host range comprises predominantly carnivores. Canine distemper virus (CDV), an enveloped, negative-sense RNA virus, infects different cell types, including epithelial, mesenchymal, neuroendocrine and hematopoietic cells of various organs and tissues. CDV infection of dogs is characterized by a systemic and/or nervous clinical course and viral persistence in selected organs including the central nervous system (CNS) and lymphoid tissue. Main manifestations include respiratory and gastrointestinal signs, immunosuppression and demyelinating leukoencephalomyelitis (DL). Impaired immune function, associated with depletion of lymphoid organs, consists of a viremia-associated loss of lymphocytes, especially of CD4+ T cells, due to lymphoid cell apoptosis in the early phase. After clearance of the virus from the peripheral blood an assumed diminished antigen presentation and altered lymphocyte maturation cause an ongoing immunosuppression despite repopulation of lymphoid organs. The early phase of DL is a sequel of a direct virus-mediated damage and infiltrating CD8+ cytotoxic T cells associated with an up-regulation of pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-12 and a lacking response of immunomodulatory cytokines such as IL-10 and transforming growth factor (TGF)-β. A CD4+-mediated delayed type hypersensitivity and cytotoxic CD8+ T cells contribute to myelin loss in the chronic phase. Additionally, up-regulation of interferon-γ and IL-1 may occur in advanced lesions. Moreover, an altered balance between matrix metalloproteinases and their inhibitors seems to play a pivotal role for the pathogenesis of DL. Summarized, DL represents a biphasic disease process consisting of an initial direct virus-mediated process and immune-mediated plaque progression. Immunosuppression is due to early virus-mediated lymphocytolysis followed by still poorly understood mechanisms affecting antigen presentation and lymphocyte maturation.     

IgG autoantibodies directed against desmoglein 3 cause dissociation of keratinocytes in canine pemphigus vulgaris and paraneoplastic pemphigus

Pemphigus is a group of autoimmune blistering diseases of the skin and mucous membranes. In human patients with pemphigus vulgaris (PV) and paraneoplastic pemphigus (PNP), IgG autoantibodies against desmoglein (Dsg) 3 and Dsg1 play pathogenic roles in blister formation. In contrast, the target for IgG autoantibodies that induce keratinocyte dissociation has not been elucidated in canine pemphigus. The aim of the present study was to determine whether anti-Dsg IgG autoantibodies are present and disrupt the cell-cell adhesion of keratinocytes in canine PV and PNP. The extracellular domains of canine Dsg3 were recognized by IgG in 3/5 (60%) canine PV sera tested. IgG against the extracellular domains of canine Dsg1 was detected exclusively in two dogs that had PV with the mucocutaneous phenotype. In addition, anti-Dsg3 IgG was identified in canine PNP serum. Furthermore, incubation of normal human keratinocytes (NHK) with mucocutaneous canine PV serum and canine PNP serum resulted in dissociation of the NHK sheets, whereas the removal of anti-Dsg3 IgG from these canine sera blocked this dissociation. The present study indicates for the first time that circulating anti-Dsg3 IgG antibodies capable of dissociating keratinocytes are present in dogs with PV and PNP.     

Observations on the pathology of canine microsporidiosis.

The available literature on canine microsporidiosis indicates that this disease, primarily of young dogs, is a distinct clinicopathological entity. It has been confused with canine distemper and rabies, and must be differentiated from toxoplasmosis. Information available on the spectrum of pathological change associated with this disease is incomplete but a distinct pattern emerges from a study of the reports. The aetiological agent appears to have a predilection for the central nervous system and kidneys, but other tissues and organs, and especially the liver, may also be infected. Vasculitis and perivasculitis, which may include fibrinoid necrosis, seem to be a basic lesion. Cellular inflammation ranges from polymorphonuclear leukocyte infiltration in areas of necrosis to focal granulomas. There may be no cellular reaction to compact groups of organisms. Histopathological and ultrastructural studies of this case augment our knowledge of the pathological changes seen with canine microsporidiosis.     

Upregulation of c-Myc may contribute to the pathogenesis of canine pemphigus vulgaris

The pathomechanism in human pemphigus vulgaris (PV) has recently been described to rely on generalized c-Myc upregulation in skin and oral mucosa followed by hyperproliferation. Here we assessed whether dogs suffering from PV present the same pathological changes as described for human patients with PV. Using immunofluorescence analysis on patients' biopsy samples, we observed marked nuclear c-Myc accumulation in all layers of the epidermis and oral mucosa in all (3/3) dogs analysed. In addition, c-Myc upregulation was accompanied by an increased number of proliferating Ki67-positive cells. These molecular changes were further paralleled by deregulated expression of wound healing and terminal differentiation markers as observed in human PV. Together these findings suggest a common pathomechanism for both species which is of particular relevance in the light of the recently discussed novel therapeutic strategies aiming at targeting PV antibody-induced signalling cascades.     

Direct and indirect lymphocyte participation in the immunity and immunopathology of tropical canine pancytopenia—A review

Erlichia canis, a rickettsial pathogen which infects monocytes, induces generalized lymphocyte activation. Activated T lymphocytes differentiate into effector cells capable of destroying infected and uninfected monocytes and platelets. Activated B lymphocytes differentiate into plasma cells associated with plasmocytosis, hypergammaglobulinemia with high levels of specific antibody and a platelet migration inhibition factor. These effector mechanisms, aimed at parasite destruction, contribute to the pathogenesis of acute tropical canine pancytopenia and do not completely eliminate the etiologic agent. A carrier state of ‘infection-immunity’ exists between the immunocompetent host and virulent parasite. E. canis has evolved mechanisms of ‘tolerant-symbiosis’ with hostile macrophages and other effector cells in the immune host.     

Observations on epiphyseal fusion of the canine appendicular skeleton

Abstract— A radiographic study of epiphyseal union of the canine appendicular skeleton—and it is reported that variation in the ossification pattern exists between siblings, that there is a wider difference between unrelated dogs of the same breed and a marked discrepancy between randomly selected dogs. Thus this criterion can only be used at best, as a crude indication of the age of a puppy. Résumé— Une étude radiographique de l'union epiphysienne du squelette appendiculaire du chien —il est rapporté qu'il existe une variation dans le schéma de Possification chez les enfants de méCme parents, qu'il y a une plus ample différence entre les chiens non-apparentés et appartenant à la méCme race et une divergence très marquee entre des chiens choisis au hasard. Par ce fait, ces criteriums ne peuvent éCtre employés qu'au mieux comme indication possible de l'ǎge du chiot. Zusammenfassung— Eine radiographische Studie über die Knochenendevereinigung des appendikularen Hundeskeletts—es wird auch berichtet, dass Verände rungen in den Verknöcherungsschemen bei Geschwisterhunden vorkommen und ein grösserer Unterschied zwischen nicht-verwandten Hunden derselben Rasse sowie ein auffallender Widerspruch bei aufs Geradewohl gewählten Hunden besteht. Daher kann dieses Kriterium im günstigsten Falle lediglich als grobe Andeutung für das Alter des jungen Hundes dienen.     

Observations on the use of an inactivated canine parvovirus vaccine

Data are presented on studies of field and experimental use of a formalin-inactivated canine parvovirus vaccine. There was an absolute correlation between a single successful vaccination and subsequent protection against clinical disease. Unsuccessful vaccinations were consistently associated with the presence of maternal antibody at the time of vaccination. The vaccine induced an antibody response within two days and anamnestic responses within 24 hours. It is suggested that a single successful vaccination probably protects against clinical parvovirus disease for life.     

Ultrastructural localization of pemphigus vulgaris antigen on canine keratinocytes in vivo and in vitro

Pemphigus antigens were localized, by use fo immunoelectron microscopy, on canine keratinocytes in vivo on esophageal mucosa and in vitro on established cultured keratinocytes. Convalescent sera from a human being with pemphigus vulgaris and a human being with pemphigus foliaceus reacted with the interdesmosomal cytoplasmic keratinocyte membrane of canine esophagus. Cultured canine keratinocytes expressed the pemphigus vulgaris antigen in a similar pattern, but did not carry the pemphigus foliaceus antigen. The differential presence of cell surface antigens and its relation to various forms of the disease are discussed.     

Canine pemphigus vulgaris treated with gold salt therapy

A nine year old spayed female Collie was diagnosed as having pemphigus vulgaris. Response to corticosteroid and antibiotic therapies was unsatisfactory. Aurothioglucose therapy was used later as the sole treatment. The dog achieved a complete remission lasting at least ten months.     

Altered immunohistochemical staining for desmoglein in skin biopsies in canine pemphigus foliaceus.

In this study, 50 cases of canine pemphigus foliaceus and 49 cases of canine superficial pyoderma were examined by immunohistochemical staining for patterns of desmoglein expression. In 31/50 (62%) of pemphigus foliaceus cases, there was an altered staining pattern for desmoglein consisting of distinct clumped deposits at the periphery of keratinocytes and/or dark cytoplasmic staining of acantholytic cells (consistent with internalization of desmoglein). In contrast, desmoglein staining in biopsies from cases of superficial pyoderma was diffusely pale without evidence for clumping or distinct internalization. This study demonstrates that epidermal desmoglein expression is altered in some cases of pemphigus foliaceus in dogs and suggests that immunohistochemical staining for this protein may be useful in diagnosis.