Novel immunotherapies for immune-mediated haemolytic anaemia in dogs and people

Swann, James; Garden, Oliver A.

doi:10.1016/j.tvjl.2015.10.022

Cited by 9 publications

(6 citation statements)

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“…For example, systemic GCs are commonly used as a first‐line treatment for IMHA, one of the most common autoimmune diseases diagnosed in dogs (Skelly & Swann, ). The ultimate treatment goals of immunosuppression are to provide relief of clinical symptoms, and to control pathologic inflammation and disease processes, while minimizing significant toxicity and side effects including nephrotoxicity, opportunistic infections, diminished tumour immunosurveillance, serum sickness, anaphylaxis and neurotoxicity (Swann & Garden, ; Viviano, ).…”

Section: Discussionmentioning

confidence: 99%

“…Immune cytopenias are conditions defined by the reduction of one or more mature blood cell types, such as platelets in immune thrombocytopenia (IMTP) and red blood cells in immune‐mediated haemolytic anaemia (IMHA) (Seidel, ; Swann & Garden, ). The mainstay treatment for IMTP and IMHA is GCs, often co‐administered with other immunosuppressive agents, but optimal treatment algorithms for dogs remain poorly defined (Chikazawa & Dunning, ; Garden & Kidd, ; Piek, ; Skelly & Swann, ; Swann & Skelly, ).…”

Section: Mycophenolic Acid and Immunosuppression In Dogsmentioning

confidence: 99%

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Mycophenolic acid in patients with immune‐mediated inflammatory diseases: From humans to dogs

Klotsman

Sathyan

Anderson

et al. 2018

Vet Pharm & Therapeutics

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Mycophenolic acid (MPA), a noncompetitive, selective and reversible inhibitor of inosine 5′‐monophosphate dehydrogenase (IMPDH), is an immunosuppressive agent that has a long history in medicine. Mechanistically, the inhibition of IMPDH leads to the selective and eventual arrest of T‐ and B‐lymphocyte proliferation. Mycophenolate mofetil (MMF), the first MPA‐based product to receive marketing approval over two decades ago, was originally indicated for the prophylaxis of organ rejection in human transplant patients. Given its broad immunosuppressive properties and ability to selectively inhibit lymphocyte division and effector functions, the clinical utility of MPA was subsequently explored in a host of autoimmune diseases. Human clinical studies have shown MPA to be safe and effective and support its off‐label administration for immune‐mediated diseases such as lupus, myasthenia gravis and atopic dermatitis. MMF became generically available in the United States in 2008, and its clinical utility is increasingly being explored as a treatment option for dogs with immune‐mediated diseases. This review summarizes the available literature for MPA pharmacokinetics and pharmacodynamics, and the current status of MPA as a treatment for client‐owned dogs diagnosed with immune‐mediated diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Mycophenolic Acid and Immunosuppression In Dogsmentioning

confidence: 99%

Mycophenolic acid in patients with immune‐mediated inflammatory diseases: From humans to dogs

Klotsman

Sathyan

Anderson

et al. 2018

Vet Pharm & Therapeutics

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“…Greater understanding of abnormalities in peripheral immune tolerance in dogs with IMHA may guide future attempts to produce therapeutic agents that might control the autoimmune response [16]. This approach has been fructiferous in people, in whom recombinant monoclonal antibodies against TNFα and CD20 (a molecule exclusively expressed on the surface of B cells) are employed in treatment of warm autoimmune haemolytic anaemia (wAIHA) [17], a disease that closely resembles IMHA in dogs.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Swann

Woods

et al. 2016

PLoS ONE

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BackgroundImmune-mediated haemolytic anaemia (IMHA) is reported to be the most common autoimmune disease of dogs, resulting in significant morbidity and mortality in affected animals. Haemolysis is caused by the action of autoantibodies, but the immunological changes that result in their production have not been elucidated.AimsTo investigate the frequency of regulatory T cells (Tregs) and other lymphocyte subsets and to measure serum concentrations of cytokines and peripheral blood mononuclear cell expression of cytokine genes in dogs with IMHA, healthy dogs and dogs with inflammatory diseases.Animals19 dogs with primary IMHA, 22 dogs with inflammatory diseases and 32 healthy control dogs.MethodsResidual EDTA-anti-coagulated blood samples were stained with fluorophore-conjugated monoclonal antibodies and analysed by flow cytometry to identify Tregs and other lymphocyte subsets. Total RNA was also extracted from peripheral blood mononuclear cells to investigate cytokine gene expression, and concentrations of serum cytokines (interleukins 2, 6 10, CXCL-8 and tumour necrosis factor α) were measured using enhanced chemiluminescent assays. Principal component analysis was used to investigate latent variables that might explain variability in the entire dataset.ResultsThere was no difference in the frequency or absolute numbers of Tregs among groups, nor in the proportions of other lymphocyte subsets. The concentrations of pro-inflammatory cytokines were greater in dogs with IMHA compared to healthy controls, but the concentration of IL-10 and the expression of cytokine genes did not differ between groups. Principal component analysis identified four components that explained the majority of the variability in the dataset, which seemed to correspond to different aspects of the immune response.ConclusionsThe immunophenotype of dogs with IMHA differed from that of dogs with inflammatory diseases and from healthy control dogs; some of these changes could suggest abnormalities in peripheral tolerance that permit development of autoimmune disease. The frequency of Tregs did not differ between groups, suggesting that deficiency in the number of these cells is not responsible for development of IMHA.

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“…Insbesondere bei Autoimmunerkrankungen, wie der immunvermittelten hämolytischen Anämie (IMHA), die eine langfristige und potente Therapie erfordern, ist bei den "klassischen", breit aufgestellten Immunsuppressiva (z. B. Glukokortikoide) mit einem großen Nebenwirkungspotenzial zu rechnen (99). Aus diesem Grund ist das Verständnis der zugrundeliegen-den Ätiologien immunvermittelter Erkrankungen und einer gezielteren medikamentösen Beeinflussung des Immunsystems bzw.…”

Section: Introductionunclassified

“…Aus diesem Grund ist das Verständnis der zugrundeliegen-den Ätiologien immunvermittelter Erkrankungen und einer gezielteren medikamentösen Beeinflussung des Immunsystems bzw. einer direkten Wirkung auf spezielle Entzündungszellpopulationen erstrebenswert (99).…”

Section: Introductionunclassified

Immunsuppressive Therapie bei Hunden und Katzen. Eigenschaften von Wirkstoffen und ihre Anwendung bei verschiedenen immunvermittelten Erkrankungen

Rieder¹,

Mischke²

2018

Tierarztl Prax Ausg K

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ZusammenfassungTierärzte werden regelmäßig mit der Diagnose und Therapie immunvermittelter Erkrankungen konfrontiert. Zu den häufigeren Erkrankungen gehören die immunvermittelte hämolytische Anämie, die immunvermittelte Thrombozytopenie und Polyarthritis. Aufgrund ihrer Verfügbarkeit, Effizienz und schnellen Wirkung sind Glukokortikoide Mittel der ersten Wahl. Einige Patienten mit immunvermittelten Erkrankungen sprechen jedoch nicht auf eine alleinige Therapie mit Glukokortikoiden an. Bei anderen Patienten muss infolge schwerwiegender Nebenwirkungen zeitnah eine Dosisreduktion der Glukokortikoide erfolgen. In solchen Fällen ist die Anwendung ergänzender Medikamente indiziert. Für Ciclosporin gibt es zugelassene Präparate in der Veterinärmedizin. In der Literatur ist auch der Einsatz von Azathioprin, Mycophenolat-Mofetil und humanen Immunglobulinen beschrieben. Der Artikel gibt einen Überblick über die Wirkmechanismen einzelner immunmodulierender Substanzen sowie deren in der aktuellen Literatur beschriebenen Einsatz bei ausgewählten Erkrankungen.

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Novel immunotherapies for immune-mediated haemolytic anaemia in dogs and people

Cited by 9 publications

References 98 publications

Mycophenolic acid in patients with immune‐mediated inflammatory diseases: From humans to dogs

Mycophenolic acid in patients with immune‐mediated inflammatory diseases: From humans to dogs

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Immunsuppressive Therapie bei Hunden und Katzen. Eigenschaften von Wirkstoffen und ihre Anwendung bei verschiedenen immunvermittelten Erkrankungen

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