Comparison of polyclonal and monoclonal antibody assays for serum amyloid A in cats: a study based on an automated turbidimetric immunoassay in a primary care veterinary hospital.

OBJECTIVE: Comparing the utility of the anti-human serum amyloid A (SAA)-specific monoclonal and polyclonal antibodies assays (LZ-SAA) with the pure monoclonal anti-human antibody assays (VET-SAA) during clinical practice in primary care hospital populations by measuring SAA measurement in healthy and diseased domestic cats. ANIMALS: 52 healthy and 185 diseased client-owned cats. METHODS: SAA concentration was measured using different LZ-SAA and VET-SAA measurements for healthy and various diseased cats. Sensitivity, specificity, and accuracy were calculated for each disease. RESULTS: VET-SAA has higher sensitivity than LZ-SAA for the most common diseases presenting to primary care veterinary hospitals, including chronic kidney disease, tumors, and gingivostomatitis. Our results reveal the capability of detecting low SAA concentrations in healthy and diseased cats using VET-SAA in contrast to LZ-SAA, which found elevations of SAA concentrations only in diseased cats. CLINICAL RELEVANCE: Our findings indicate that switching to the new VET-SAA instead of the conventional LZ-SAA will likely enhance the diagnostic performance in primary care veterinary hospitals.

Immune-mediated hemolytic anemia and pure red cell aplasia in a Jack Russell Terrier during treatment for hypoadrenocorticism.

An 11-year-old neutered male Jack Russell Terrier was presented to Yuki Animal Hospital for regenerative anemia during the treatment of hypoadrenocorticism. A blood smear examination showed spherocytes, polychromatic erythrocytes, and erythrocyte ghosts. The direct agglutination test was positive at 37°C. The dog was then diagnosed with immune-mediated hemolytic anemia (IMHA). Although prednisolone and mycophenolate mofetil were administered, the hematocrit and reticulocyte count decreased, and nonregenerative anemia developed. A bone marrow examination was performed to diagnose the cause of the nonregenerative anemia. Histologic and cytologic bone marrow examination revealed a normocellular to hypercellular medulla with severe erythroid hypoplasia. No proliferation of lymphocytes or lymphoblast-appearing cells was observed. This dog was diagnosed with pure red cell aplasia (PRCA). Despite treatment with immunosuppressive agents, the patient died of thrombosis. Although these associations were unclear, this is the first report of PRCA diagnosis following IMHA and while treating hypoadrenocorticism.

Complete remission of two canine cases with precursor-targeted immune-mediated anemia after combination therapy with prednisolone, cyclosporine, and oclacitinib.

Background: Precursor-targeted immune-mediated anemia (PIMA) has been described in dogs presenting with nonregenerative anemia and evidence of ineffective erythropoiesis. Although it has been suggested that its occurrence may be related to the immune targeting of erythroid precursors, this pathogenesis has not been established. PIMA is mainly treated with glucocorticoids, and in cases where glucocorticoids alone are not effective, immunosuppressants are also used as combination therapy. However, not all cases of PIMA go into remission after these treatments. Case Description: Two dogs with severe nonregenerative anemia diagnosed as PIMA based on the results of clinical pathological examinations, including bone marrow examination, were treated with whole-blood transfusion and immunosuppressive doses of prednisolone, mycophenolate mofetil, and cyclosporine. However, these treatments failed to achieve remission of PIMA. Therefore, concomitant administration of oclacitinib, which is a Janus kinase-1 inhibitor that has been applied recently to the treatment of immune-mediated diseases, was performed; this combined regimen improved the anemia and achieved complete remission of PIMA. Conclusion: Oclacitinib may be an option for the treatment of PIMA in dogs failing to achieve remission with conventional immunosuppressive therapy.

Trismus due to myotonia associated with hyperadrenocorticism in a dog.

We present the report of trismus due to hyperadrenocorticism-associated myotonia diagnosed by electromyography in a dog. An intact female Miniature Dachshund, 13 years and 9 months old, presented with stiff gait and trismus as well as polyuria and polydipsia. Abdominal ultrasonography showed enlarged adrenal glands. An adrenocorticotropic hormone stimulation test revealed an exaggerated response. Based on these findings, this case was diagnosed with hyperadrenocorticism. Electromyography revealed myotonic discharge in the temporalis muscle and limbs. Therefore, trismus was considered to be caused by hyperadrenocorticism-associated myotonia, and the case was treated with oral trilostane (1.3 mg/kg, once daily). During the 4-month follow-up period, despite the partial improvement in stiff gait, trismus did not recover. Long-term data on more cases are warranted to assess the prognosis and clinical characteristics of trismus due to hyperadrenocorticism-associated myotonia.

Activation of the unfolded protein response in canine degenerative myelopathy.

Canine degenerative myelopathy (DM) is an adult-onset progressive and fatal neurodegenerative disorder. Superoxide dismutase 1 (SOD1) mutations have been reported in affected dogs and immunohistochemical analyses revealed the accumulation of mutant SOD1 (E40K) in spinal neurons and astrocytes. Therefore, this disease is regarded as a unique spontaneous large-animal model of SOD1-mediated amyotrophic lateral sclerosis (ALS) in humans. Recent studies reported that endoplasmic reticulum (ER) stress is a key pathomechanism underlying motor neuron death in ALS. The present study demonstrated the up-regulated expression of the ER stress marker GRP78/BiP (BiP) in the spinal cords of DM-affected dogs. Immunohistochemistry of serial spinal cord sections revealed strong BiP expression in microglia and astrocytes in DM compared to normal control dogs, whereas such difference was not observed in spinal neurons. The results of transcriptional analyses of DM spinal tissues showed increased expression levels of apoptosis signal-regulating kinase 1 (ASK1) and spliced X-box binding protein (XBP1s). E40K-transfected Neuro2A cells expressed higher levels of BiP than wild-type SOD1-transfected cells. These results suggest that the activation of the unfolded protein response (UPR) in microglia and astrocytes plays crucial roles in UPR-mediated inflammation in the spinal cords of DM-affected dogs.