Squamous Cell Carcinoma Arising in Chronic Discoid Lupus Erythematosus Nasal Lesions in Two German Shepherd Dogs

Résumé— Un épithélioma spinocellulaire s'est développé sur des lésions chroniques incontrôlées de lupus erythémateux discoïde chez deux chiens bergers allemands. Les chiens n'avaient reçu ni traitement ni photoprotection pour leurs lésions de lupus discoïde durant les 4 à 6 ans précédant l'apparition clinique d'épithéliomas spinocellulaires. [Scott, D.W., Miller, W.H., Jr. Squamous cell carcinoma arising in chronic discoid lupus erythematosus nasal lesions in two German Shepherd Dogs (Un épithélioma spinocellulaire suivenant sur des lesions de lupus erythémateux discoïde chroniques chez deux bergers allemands).
Resumen— Dos perros de raza Pastor Alemán desarrollaron carcinomas de células escamosas en lesiones crónicas del tipo lupus eritematoso discoide. Estos animales no habian recibido tratamiento ni protección solar del cuadro de lupus eritematoso discoide en los 4 a 6 años previos al desarrollo del carcinoma escamoso. [Scott, D.W., Miller, W.H., Jr. Squamous cell carcinoma arising in chronic discoid lupus erythematosus nasal lesions in two German Shepherd Dogs (Carcinoma de células escamosas a partir de lesiones crónicas nasales del tipo lupus eritematoso discoide en dos perros Pastor Alemán).
Abstract— Squamous cell carcinoma developed in the chronic, uncontrolled nasal lesions of discoid lupus erythematosus in two German Shepherd Dogs. The dogs had received no treatment nor photoprotection for their discoid lupus erythematosus for 4–6 years prior to the clinical onset of squamous cell carcinoma.     

Discoid Lupus Erythematosus in Cats

Abstract— The clinical and histopathological features of discoid lupus erythematosus (DLE) are described in four European short-haired cats. Pinnal involvement seems to be highly predictable in feline DLE. In addition an indication exists for the initiating role of exposure to the sun in this disease. Résumé— Les aspects cliniques et histopathologiques du lupus érythémateux discoide (DLE) sont décrits chez quatre chats européens à poils courts. L'atteinte du pavilion auriculaire semble très fréquente dans le DLE félin. En outre, l'exposition au soleil semble jouer un röle déterminant dans cette entité nosologique. Zusammenfassung— Die klinischen und histopathologischen Merkmale des diskoiden Lupus erythematosus (DLE) bei vier Europäisch-Kurzhaarkatzen werden beschrieben. Beim felinen DLE scheint die Pinna regelmäßig mitbetroffen zu sein. Nach dieser Untersuchung besteht Anlaß zur Vermutung, daß die Sonnenexposition bei dieser Krankheit eine auslösende Rolle spielt.     

Interaction of nucleophilic compounds with complement component C4

Drugs which induce systemic lupus erythematosus as a toxic side effect have been shown to inhibit the covalent binding of C4, which is an important event in immune complex clearance in normal individuals. Human C4 is encoded at two polymorphic loci, C4A and C4B within the Major Histocompatibility Complex and patients with idiopathic SLE are more likely to have a non-functional (null) C4A gene. The C4A and C4B gene products differ in reactivity with C4A being more reactive with nitrogen nucleophiles, including hydralazine and isoniazid (drugs which induce SLE), than with oxygen nucleophiles. We have established an assay system which allows the effect of nucleophiles on C4 in animal sera to be investigated. It has been found that in comparing reactivity of guinea-pig C4 with human C4A and human C4B that guinea-pig C4 is like human C4A and shows greater reactivity towards nitrogen nucleophiles than towards oxygen nucleophiles. This suggests that the guinea-pig should be a good animal model for drug-induced SLE.     

Subgroups of canine antinuclear antibodies in relation to laboratory and clinical findings in immune-mediated disease

Background:  Autoimmune system diseases in dogs are commonly referred to as systemic lupus erythematosus (SLE), with a positive antinuclear antibody (ANA) test as a hallmark. In human patients, other systemic ANA-positive diseases with overlapping diagnostic features, referred to as SLE-related diseases, are described.  Objectives:  The objective of this study was to investigate whether different patterns of ANA reactivity represent different systemic autoimmune diseases in dogs. Methods:  Dogs with serum positive for ANA by indirect immunofluorescence (IIF-ANA, titer ≥1:100) (n=56) were identified retrospectively from the patient population at the Department of Small Animal Clinical Sciences, Swedish University of Agricultural Sciences. Dogs were grouped on the basis of ANA staining patterns, and the results of immunodiffusion tests. Clinical, hematologic, serum biochemical, radiologic, and pathologic examinations were described for each group.  Results:  Dogs with a chromosomal–positive, homogeneous ANA staining pattern (n=14) had clinical signs involving multiple organ systems; 8 dogs were anemic. Dogs with a speckled IIF-ANA staining pattern (n=42) primarily had clinical signs of musculoskeletal disorders, fatigue and fever. Precipitating antibodies by immunodiffusion were found only in dogs with a speckled IIF-ANA staining pattern and comprised 4 different subgroups based on antigen specificity. Conclusions: In dogs with homogeneous IIF-ANA staining, SLE is a probable diagnosis because of the diversity of clinical manifestations and autoantibody reactivity against chromosomal antigens. Dogs with a speckled IIF-ANA pattern may have SLE-related diseases, which, in turn, may be correlated with different immunodiffusion subgroups. These syndromes had overlapping clinicopathologic features, as described for human patients.     

Gene expression pattern of periphery blood mononuclear cells in patients with active lupus nephritis

AIM: To find new gene function associate with active lupus nephritis (LN) through study on the difference in gene expression of peripheral blood mononuclear cells between LN patients and healthy controls by gene chip. METHODS: The CSC-GE-80 chip containing 8 000 spots of cDNAs were used to investigate the difference of the expression. Both the total RNA from peripheral blood mononuclear cells of active LN patients and healthy donors were reversely transcribed to cDNA with the incorporation of fluorescent( cy3 and cy5) labeled dCTP to prepare the hybridization probes. After hybridization, the gene chip was scanned for the fluorescent intensity. The differentially expressed genes were screened. We repeated that in three groups of LN patients and healthy controls, respectively, and only the genes that have differential expression in all three chips were considered associated with LN. RESULTS: 75 genes were identified to be differently expressed in all three groups of LN patients as compared with healthy controls, including 42 up-regulated genes and 33 down-regulated ones. CONCLUSION: The present study represents a global view of gene expression of LN and provides important clues for further study of LN related genes. And it also suggests defensin α₁, S100A8, S100A9 may be involved in the pathogenesis of LN.     

Activation of Akt signal pathway cascades in kidney tissue in murine chronic graft-versus-host disease lupus nephritis and its regulation by prednisone

AIM:To examine whether Akt signal pathway proteins, including Akt, NF-κB and IκBα, are activated in kidney tissue of murine chronic graft-versus-host disease (GvHD) lupus nephritis in vivo, and whether prednisone suppresses activation of them.METHODS:Akt activity and phosphorylated IκBα were detected by Western-blot. Activation of NF-κB was detected by electropheretic mobility shift assay (EMSA). RESULTS:Activity of Akt, NF-κB and phosphorylated IκBα were significantly increased in kidney tissue of murine chronic graft-versus-host disease (GvHD) in 8th week and 12th week after monocell injection, respectively. However, they were no significant elevation in 16th week, when compared with controls. Prednisone treatment significantly prevented the increase in serum anti-dsDNA antibody level, urinary protein excretion and glomerular cell proliferation in GvHD mice, indicating the beneficial effects of prednisone on this model. Prednisone also significantly suppressed the increase in the activities of glomerular Akt, NF-κB and phosphorylated IκBα. CONCLUSION:This study provides the first evidence of marked increase in glomerular Akt-NF-κB signal pathway activities in murine chronic graft-versus-host disease lupus nephritis. The beneficial effect of prednisone on this lupus nephritis model may be partially mediated by the suppression of abnormal Akt- NF-κB activation.     

Ulcerative dermatosis of the Shetland sheepdog and rough collie dog may represent a novel vesicular variant of cutaneous lupus erythematosus

A syndrome of ulcerative dermatitis (UDSSC) previously has been described as unique to the Shetland sheepdog and rough collie dog. The pathogenesis of this disease is poorly understood and it has been suggested that it may be a variant of canine dermatomyositis (DM) which is also seen in these breeds. Information on the clinical presentation and previous medical history was collected from five Shetland sheepdogs and three rough collie dogs previously diagnosed with UDSSC. Characteristic features of the disease were adult onset in the summer months with annular, polycyclic and serpiginous ulcerations distributed over sparsely haired areas of the body. Skin biopsies taken from active lesions were compared in a blinded fashion with histological sections from seven Shetland sheepdogs and one rough collie with DM. Dermatomyositis was characterized histologically as a cell poor interface dermatitis associated with follicular atrophy. In contrast, the lesional pattern of UDSSC is that of a lymphocyte-rich interface dermatitis and folliculitis with vesiculation at the dermal–epidermal junction. The authors conclude that these represent two distinct diseases and that UDSSC may be a vesicular form of cutaneous lupus erythematosus seen in the adult rough collie dog and Shetland sheepdog.     

Immunopathology of vesicular cutaneous lupus erythematosus in the rough collie and Shetland sheepdog: a canine homologue of subacute cutaneous lupus erythematosus in humans

Clinical and histological features of an erosive disease in the rough collie and Shetland sheepdog are most consistent with a vesicular variant of cutaneous lupus erythematosus (VCLE). This paper reports the immunopathological findings of canine VCLE using samples from 17 affected dogs. Lesional skin sections were stained with monoclonal antibodies specific for CD3 (11 dogs) or a panel of monoclonal antibodies specific for leukocyte antigens (two dogs). Apoptotic cells were detected using the TUNEL method in 12 cases. Direct (14 dogs) and indirect immunofluorescence tests (five dogs) were also performed. Circulating antibodies to extractable nuclear antigens (ENA) were surveyed in 11 dogs by immunoblotting and ELISA. The predominant cells at the dermal-epidermal interface were identified as CD3(+) T lymphocytes expressing CD4 or CD8 and CD1(+) dendritic antigen presenting cells. In 7/12 dogs (58%), apoptosis of basal keratinocyte nuclei was present. Up-regulation of MHCII and ICAM-1 was observed on basal keratinocytes from the two dogs examined. Direct immunofluorescence revealed deposition of immunoglobulins bound to the cytoplasm of keratinocytes (6/14 dogs; 43%), to the dermal-epidermal junction (7/14 dogs; 50%), or to superficial dermal venules (13/14 dogs; 93%). Circulating IgG auto-antibodies targeting one or more ENA were detected in nine (82%) and eight (73%) of 11 dogs by immunoblotting and ELISA, respectively. These auto-antibodies recognized Ro/SSA and/or La/SSB in four (36%) and six (55%) of 11 dogs respectively by these two methods. Altogether, results of these studies provide evidence supporting the hypothesis that canine VCLE is an immunological homologue of subacute cutaneous lupus erythematosus in humans.     

Discoid Lupus Erythematosus in Cats

Abstract— The clinical and histopathological features of discoid lupus erythematosus (DLE) are described in four European short-haired cats. Pinnal involvement seems to be highly predictable in feline DLE. In addition an indication exists for the initiating role of exposure to the sun in this disease.
Résumé— Les aspects cliniques et histopathologiques du lupus érythémateux discoide (DLE) sont décrits chez quatre chats européens à poils courts. L'atteinte du pavilion auriculaire semble très fréquente dans le DLE félin. En outre, l'exposition au soleil semble jouer un röle déterminant dans cette entité nosologique.
Zusammenfassung— Die klinischen und histopathologischen Merkmale des diskoiden Lupus erythematosus (DLE) bei vier Europäisch-Kurzhaarkatzen werden beschrieben. Beim felinen DLE scheint die Pinna regelmäßig mitbetroffen zu sein.
Nach dieser Untersuchung besteht Anlaß zur Vermutung, daß die Sonnenexposition bei dieser Krankheit eine auslösende Rolle spielt.     

Activation of farnesoid X receptor attenuates liver injury in MRL/lpr lupus mice

AIM: To observe how the activation of farnesoid X receptor (FXR) influences liver function in MRL/lpr lupus mice. METHODS: The expression of FXR at mRNA and protein levels was determined in the liver specimens of MRL/lpr mouse model.MRL/lpr mice and the control BALB/c mice received concanavalin A (ConA) to induce liver injury. The FXR agonist chenodeoxycholic acid (CDCA) was administered to MRL/lpr mice. Blood samples were taken at the time points of 0 h, 4 h, 8 h, 12 h, 16 h and 24 h after ConA injection for the detection of serum ALT, AST, IFN-γ, TNF-α and IL-6. RESULTS: FXR was down-regulated in the liver specimens of MRL/lpr mice. MRL/lpr mice were more susceptible to ConA than BALB/c mice to induce significantly higher levels of aminotransferases and inflammatory cytokines. Activation of FXR by CDCA significantly reduced the levels of aminotransferases and inflammatory cytokines IFN-γ, TNF-α and IL-6 caused by ConA injection in MRL/lpr mice. CONCLUSION: FXR activation ameliorates liver injury and suppresses the production of inflammatory cytokines, indicating that FXR protects the liver functions in lupus mice.