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DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) is a C-type lectin receptor expressed on dendritic cells and M2 macrophages, playing a key role in immune regulation and pathogen recognition. Its ability to mediate anti-inflammatory effects by interacting with specific ligands triggers pathways that suppress pro-inflammatory responses and promote tissue repair, making it a potential therapeutic target for inflammatory and autoimmune diseases. DC-SIGN homologs in various animal species share structural similarities and perform comparable immune functions, offering valuable insights into its broader application across species. By recognizing carbohydrate ligands on pathogens, DC-SIGN facilitates immune modulation, which can be harnessed for developing therapies aimed at controlling inflammation. In veterinary medicine, autoimmune and inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease, represent significant challenges, and the anti-inflammatory properties of DC-SIGN could provide new therapeutic options to improve disease management and enhance animal health. Future investigations should focus on the structural and functional analysis of DC-SIGN homologs in various species, as well as the development of preclinical models to translate these findings into clinical interventions bridging veterinary and human health.

Addison’s disease (AD) results in glucocorticoid and mineralocorticoid deficiencies and is often immune-mediated. While AD is uncommon in dogs, Nova Scotia Duck Tolling Retrievers (NSDTRs) exhibit increased incidence, suggesting genetic predisposition. Detailed clinical evaluation of 24 juvenile-onset cases revealed that while all dogs presented with adrenal insufficiency, at least 10 dogs (41.7%) had concurrent autoimmune conditions. This suggests juvenile-onset AD in NSDTRs represents part of a broader multiple autoimmune syndrome (MAS) with variable expressivity. Strikingly, NSDTRs affected by juvenile-onset AD had severely decreased lifespans, with a median survival of 2 years despite appropriate treatment. Genome-wide association identified a significant association on chromosome 27 (chr27:29,724,286, p  = 6.96 × 10 − 13 ). Whole-genome, short-read sequencing identified a recessive missense variant in RESF1 (Chr27:29,736,795). The variant exhibited 76% penetrance for early-onset disease, and the decreased penetrance was not attributable to differences in Dog Leukocyte Antigen (DLA) haplotypes. Immunohistochemistry confirmed T cell infiltration in the adrenal cortex of two unrelated affected dogs, with necropsy findings including severe bilateral lymphocytic adrenalitis, multisystemic granulomatous inflammation, and lymphoplasmacytic conjunctivitis supporting autoimmune pathogenesis. This study identifies RESF1 as a novel gene associated with autoimmune disease in NSDTRs, ranging from isolated juvenile-onset AD to multi-organ autoimmune manifestations. The findings represent a rare example of monogenic autoimmune disease and establish RESF1 as a candidate gene for further investigation of immune tolerance mechanisms.

Mesenchymal stem cells are multipotent cells, with capacity for self-renewal and differentiation into tissues of mesodermal origin. These cells are possible therapeutic agents for autoimmune disorders, since they present remarkable immunomodulatory ability. The increase of immune-mediated diseases in veterinary medicine has led to a growing interest in the research of these disorders and their medical treatment. Conventional immunomodulatory drug therapy such as glucocorticoids or other novel therapies such as cyclosporine or monoclonal antibodies are associated with numerous side effects that limit its long-term use, leading to the need for developing new therapeutic strategies that can be more effective and safe. The aim of this review is to provide a critical overview about the therapeutic potential of these cells in the treatment of some autoimmune disorders (canine atopic dermatitis, feline chronic gingivostomatitis, inflammatory bowel disease and feline asthma) compared with their conventional treatment. Mesenchymal stem cell-based therapy in autoimmune diseases has been showing that this approach can ameliorate clinical signs or even cause remission in most animals, with the exception of canine atopic dermatitis in which little to no improvement was observed. Although mesenchymal stem cells present a promising future in the treatment of most of these disorders, the variability in the outcomes of some clinical trials has led to the current controversy among authors regarding their efficacy. Mesenchymal stem cell-based therapy is currently requiring a deeper and detailed analysis that allows its standardization and better adaptation to the intended therapeutic results, in order to overcome current limitations in future trials.

Abstract Background Proteinuria is associated with autoimmune diseases in humans. There is minimal evidence in the veterinary literature on proteinuria and its association with immune-mediated disease in dogs. Hypothesis Renal proteinuria is common in dogs with immune-mediated disease. Dogs presenting with pyrexia or immune-mediated polyarthritis (IMPA) are more likely to have proteinuria. Animals One hundred and forty-four dogs with primary immune-mediated diseases. Methods Retrospective, observational study. Data collected included signalment, travel outside the United Kingdom, duration of clinical signs, diagnosis, urinalysis, and urine protein–creatinine ratio (UPCR). Non-proteinuric, mild proteinuria, moderate proteinuria, and severe proteinuria were defined as UPCR < 0.5; ≥ 0.5–1; ≥ 1–2; ≥ 2, respectively. Exclusion criteria included azotemia, hypoalbuminemia (< 2.0 g/dL), foreign travel, active urine sediment or positive culture, glucocorticoid therapy for greater than 24 h prior to presentation, or medication known to influence UPCR. Results Sixty-seven dogs were non-proteinuric (47%; 95% confidence interval [95% CI]: 38%, 55%), 25 mildly proteinuric (17%; 95% CI: 9%, 26%), 15 moderately proteinuric (10%; 95% CI: 2%, 19%), and 37 severely proteinuric (26%; 95% CI: 17%, 34%). On multiple logistic regression analysis, female dogs (odds ratio [OR]: 3.24; 95% CI: 1.49, 7.42), individuals with pyrexia (OR: 6.59; 95% CI: 3.00, 15.37), or hemoglobinuria (OR: 27.21; 95% CI: 4.79, 516.56) were more likely to have proteinuria. There was an association between steroid-responsive meningitis-arteritis and the magnitude of proteinuria on multiple linear regression (p = 0.025); this was not confirmed on multiple logistic regression. Conclusions and Clinical Importance Proteinuria is common in dogs with immune-mediated disease and can be severe. Screening for proteinuria could be considered part of the diagnostic assessment for dogs with immune-mediated disease.

The Nova Scotia Duck Tolling Retriever (NSDTR) is predisposed to immune mediated rheumatic disease (IMRD), steroid-responsive meningitis-arteritis (SRMA) and certain forms of cancer. Cytokines are the main regulators of the immune system. Interleukin 2 is a cytokine involved in activation of T regulatory cells, playing a role in central tolerance and tumor immunity. Interleukin 12 and interleukin 23 share the same subunit, p40, and are both pro-inflammatory cytokines. The aim of this study was to compare levels of IL-2 in healthy NSDTRs to those with cancer or autoimmune disease and to compare levels of IL-12/IL-23p40 in healthy NSDTRs and beagles versus NSDTRs with cancer or autoimmune disease. 62 dogs were included in the analysis of IL-12/IL-23p40; healthy NSDTRs (n = 16), healthy beagles (n = 16), NSDTRs autoimmune (n = 18) and NDSTRs lymphoma/mastocytoma (n = 12) and 68 dogs for IL-2; healthy (n = 20), autoimmune (n = 36) and lymphoma/mastocytoma/adenocarcinoma (n = 12). NSDTRs with autoimmune disease had higher levels of IL-12/IL-23p40 compared to healthy dogs (p = 0.008). NSDTRs with lymphoma also had higher levels of IL-12/IL-23p40 compared to healthy NSDTRs (p = 0.002). There was no difference in levels of IL-2 between healthy and diseased NSDTR. Statistical analysis was performed using Bonferroni corrections for multiple testing. These findings can contribute to the knowledge of autoimmune disease and cancer in dogs.

Bovine spastic paresis (BSP) is a progressive neuromuscular disease of unknown origin that causes persistent stiffness of the hind limbs. The symptoms are similar to those of human motor neuron diseases such as primary (PLS) or amyotrophic lateral sclerosis (ALS). BSP occurs worldwide in cattle production with an estimated prevalence of <1%. For Germany, this means that around 20,000 Holstein cattle are affected. BSP is generally considered a hereditary disease, but there is no prevention through breeding programs. As a result, BSP not only affects animal welfare but also leads to economic losses in milk and beef production. Here, we used transcriptomics to analyse the brainstem, spinal cord and affected gastrocnemius muscle tissue of eight animals affected by BSP and eight control animals from slaughterhouses to gain new insights into the molecular mechanisms underlying BSP. We found that the expression of several genes was significantly different in animals affected by BSP compared to control animals. Specific genes for inhibitory neurons were downregulated in the brainstems of the affected animals, namely CCK (cholecystokinin), NPY (neuropeptide Y), and SST (somatostatin). These inhibitory neurotransmitters influence cerebral movement control, among other processes. Furthermore, OOSP2 (oocyte secreted protein 2) was found to be significantly upregulated in the affected animals in all tissues. This expression could best be explained by the presence of T-follicular-helper cells which, through interleukin 21, can trigger a TH-2-dominated immune response and lead to autoimmune encephalitis. Further cases were sampled for confirmation and we detected cell infiltrates of activated microglia and T-cells in the brainstem using immunohistochemistry. Microglial foci were significantly more abundant in animals affected by BSP than control animals. We conclude that BSP is caused by an autoimmune reaction directed against inhibitory interneurons in the brainstem and is due to a combination of genetics and environmental influences. This may result in lost controlling influence on the upper motor neurons via extrapyramidal pathways and therefore triggers the specific symptoms of motor neuron disease.

Abstract Background Thrombocytosis is a hematologic abnormality in dogs that has been associated with various neoplastic, metabolic, and inflammatory conditions. Objective To classify thrombocytosis in dogs based on severity and evaluate whether there are associations between severity and underlying disease processes. Animals Seven hundred and fifteen dogs with thrombocytosis and 1,430 dogs with normal numbers of platelets. Methods Retrospective study. Medical records of dogs with increased (>500 × 103/μL; thrombocytosis group) and normal (300–500 × 103/μL; control group) platelet counts between 2011 and 2015 were reviewed. Dogs were characterized by severity of platelet increase and diagnosis. Diagnostic categories included neoplasia, endocrine disease, inflammatory disease, or miscellaneous. Results A total of 1,254 complete blood counts with thrombocytosis from 715 dogs were included in the study. Median platelet count in this population was 582 × 103/μL (500–1,810 × 103/μL). No correlation between severity of thrombocytosis and diagnosis was identified. Causes of secondary thrombocytosis included neoplasia (55.7%), endocrine disease (12.0%), and inflammatory disease (46.6%). Immune-mediated disease was common (22.2%), associated with frequent glucocorticoid administration, and had a significantly higher median platelet count (636 × 103/μL [500–1,262 × 103/μL] versus 565 × 103/μL [500–1,810 × 103/μL]) when compared to the other inflammatory processes (P < 0.001). The diagnoses in the thrombocytosis dogs differed significantly from the control population (P < 0.001). Conclusions and Clinical Importance Thrombocytosis is commonly associated with carcinoma and immune-mediated disease in dogs.

Abstract Background Autoantibody biomarkers are valuable tools used to diagnose and manage autoimmune diseases in dogs. However, prior publications have raised concerns over a lack of standardization and sufficient validation for the use of biomarkers in veterinary medicine. Objectives Systematically compile primary research on autoantibody biomarkers for autoimmune disease in dogs, summarize their methodological features, and evaluate their quality; synthesize data supporting their use into a resource for veterinarians and researchers. Animals Not used. Methods Five indices were searched to identify studies for evaluation: PubMed, CAB Abstracts, Web of Science, Agricola, and SCOPUS. Two independent reviewers (AET and ELC) screened titles and abstracts for exclusion criteria followed by full-text review of remaining articles. Relevant studies were classified based on study objectives (biomarker, epitope, technique). Data on study characteristics and outcomes were synthesized in independent data tables for each classification. Results Ninety-two studies qualified for final analysis (n = 49 biomarker, n = 9 epitope, and n = 34 technique studies). A high degree of heterogeneity in study characteristics and outcomes reporting was observed. Opportunities to strengthen future studies could include: (1) routine use of negative controls, (2) power analyses to inform sample sizes, (3) statistical analyses when appropriate, and (4) multiple detection techniques to confirm results. Conclusions These findings provide a resource that will allow veterinary clinicians to efficiently evaluate the evidence supporting the use of autoantibody biomarkers, along with the varied methodological approaches used in their development.

Background Gonadectomy is one of the most common procedures performed on dogs in the United States. Neutering has been shown to reduce the risk for some diseases although recent reports suggest increased prevalence for structural disorders and some neoplasias. The relation between neuter status and autoimmune diseases has not been explored. This study evaluated the prevalence and risk of atopic dermatitis (ATOP), autoimmune hemolytic anemia (AIHA), canine myasthenia gravis (CMG), colitis (COL), hypoadrenocorticism (ADD), hypothyroidism (HYPO), immune-mediated polyarthritis (IMPA), immune-mediated thrombocytopenia (ITP), inflammatory bowel disease (IBD), lupus erythematosus (LUP), and pemphigus complex (PEMC), for intact females, intact males, neutered females, and neutered males. Pyometra (PYO) was evaluated as a control condition. Results Patient records (90,090) from the William R. Pritchard Veterinary Medical Teaching Hospital at the University of California, Davis from 1995 to 2010 were analyzed in order to determine the risk of immune-mediated disease relative to neuter status in dogs. Neutered dogs had a significantly greater risk of ATOP, AIHA, ADD, HYPO, ITP, and IBD than intact dogs with neutered females being at greater risk than neutered males for all but AIHA and ADD. Neutered females, but not males, had a significantly greater risk of LUP than intact females. Pyometra was a greater risk for intact females. Conclusions The data underscore the importance of sex steroids on immune function emphasizing a role of these hormones on tissue self-recognition. Neutering is critically important for population control, reduction of reproductive disorders, and offers convenience for owners. Despite these advantages, the analyses of the present study suggest that neutering is associated with increased risk for certain autoimmune disorders and underscore the need for owners to consult with their veterinary practitioner prior to neutering to evaluate possible benefits and risks associated with such a procedure.

Abstract Background Opportunistic invasive fungal infections (OIFIs) occur in dogs administered immunosuppressive medications. However, the epidemiology of OIFIs among dogs undergoing immunosuppressive treatment is poorly understood. The aims of this study were to (1) estimate the incidence of OIFIs among dogs diagnosed with certain immune-mediated diseases and treated with immunosuppressive drugs, and (2) determine if administration of particular drug(s) was a risk factor for OIFIs. Hypothesis Dogs receiving cyclosporine treatment (alone or as part of a multidrug protocol) are at higher risk of developing OIFIs. Animals One hundred and thirteen client-owned dogs diagnosed with select immune-mediated diseases: 42 with IMHA, 29 with ITP, 34 with IMPA, and 8 with Evans syndrome. Methods Retrospective cohort study. Medical records of dogs presenting to the Texas A&M University, Veterinary Medical Teaching Hospital between January 2008 and December 2015, and treated for 1 or more of IMHA, IMPA, ITP, or Evans syndrome were retrospectively reviewed. Dogs that did not develop an OIFI were excluded if they died, were euthanized, or were lost to follow-up within 120 days of initiation of immunosuppressive treatment. Results Fifteen dogs of 113 (13%) were diagnosed with an OIFI based on 1 or more of cytology, culture, or histopathology. The odds of developing an OIFI were greater among dogs that were treated with cyclosporine (OR = 7.1, P = 0.017; 95% CI, 1.5–34.4) and among male dogs (OR = 5.1, P = 0.018; 95% CI, 1.4–17.9). Conclusions and Clinical Importance OIFIs were significantly more likely in male dogs and those receiving cyclosporine. It is important to consider OIFIs as a potential complication of immunosuppressive treatment, particularly cyclosporine.