Hypersensitivity Clinical Correlates PDF

Hypersensitivity Reactions Clinical Correlates Jennifer Prieto, DVM, PhD, DACVIM (SAIM) pollev.com/jpvtmed  Learning Objectives 1. Describe the immune mechanisms, including type of hypersensitivity reaction, associated with (1) immune-mediated hemolytic anemia (IMHA...

Hypersensitivity Reactions Clinical Correlates Jennifer Prieto, DVM, PhD, DACVIM (SAIM) pollev.com/jpvtmed  Learning Objectives 1. Describe the immune mechanisms, including type of hypersensitivity reaction, associated with (1) immune-mediated hemolytic anemia (IMHA, both extravascular and intravascular hemolysis), (2) myasthenia gravis (MG), & (3) immune-mediated polyarthritis (IMPA). 2. Identify four broad categories of underlying triggers (also called associations) that can lead to the development of immune-mediated disease. 3. Summarize how key diagnostic tests can provide evidence that immune- mediated disease is occurring (IMHA: red blood cell morphologic abnormalities, serum or urine abnormalities consistent with hemolysis, agglutination; MG: acetylcholine receptor antibody test; IMPA: joint cytology) *Note: Learning objectives generally describe the minimum knowledge needed to pass the course.  Immune-Mediated Disease occurs when self-tolerance to self-antigens is lost and the adaptive immune system is inadvertently directed towards normal components of the healthy individual Immune-mediated diseases are type II, III, IV hypersensitivity reactions  Gracie 4-year-old FS Golden Retriever Lethargy that progressed to collapse Pale and jaundiced mucous membranes Febrile (temperature 103.2F) Pigmenturia (port wine color)  Gracie 4-year-old FS Golden Retriever Hematocrit: 20% (RR: 41-58) Reticulocytes: 221k/uL (RR: 11-92) RBC comments: spherocytes, ghost cells. agglutination Total bilirubin: 10.9mg/dL (RR:X-X) Why is Gracie anemic?  Immune-Mediated Hemolytic Anemia A disease in which an individual’s immune system destroys their red blood cells This immune-mediated red blood cell destruction can occur via: Extravascular hemolysis Extravascular hemolysis Extravascular hemolysis Extravascular hemolysis Extravascular hemolysis – Clinical signs Intravascular hemolysis Intravascular hemolysis Intravascular hemolysis Intravascular hemolysis Intravascular hemolysis Intravascular hemolysis  Intravascular hemolysis – Clinical Signs ghost cells  Gracie Clinical findings consistent with hemolysis Intravascular hemolysis Extravascular hemolysis  Gracie Clinical findings consistent with immune-mediated destruction of red blood cells  Agglutination of Red Blood Cells phenomenon were red blood cells stick together in 3D clumps due to the binding of antibodies to the red blood cells Associative vs. non-associative immune-mediated disease Associative A comorbidity & putative trigger for the development of immune-mediated disease is identified Non-associative No putative trigger identified 4 categories of associative causes for immune-mediated disease  Examples of how tolerance to “self” is lost Bystander Effect Molecular Mimicry Inflammatory mediators released Some pathogens express antigens during infection or inflammatory similar to host antigens in effort to response can activate cells that are evade the host system & under not specific to the antigen that some circumstances can induce innated the initial immune response immune-mediated disease Haptenization Epitope Unmasking Haptens are small molecules that Some proteins are not normally do not trigger an immune presented to the immune system - response in isolation, but are these antigen portions are perceived immunogenic when bound to a as “non-self” if exposed to the protein (an example is penicillin immune system with cell damage bound to RBC membrane protein)  Gracie 4-year-old FS Golden Retriever Infectious disease testing: 4DX negative except for Lyme (historical +), Babesia PCR negative Neoplasia screening: Normal thoracic radiographs & abdominal ultrasound No medications or vaccinations administered in the last month Non-associative IMHA  Gracie 4-year-old FS Golden Retriever Multiple red blood cell transfusions. & supportive care Immunosuppressive medications Remission achieved & successfully tapered off of immunosuppressant medications  Gracie What Gracie has demonstrated Immune-mediated hemolytic anemia is an example of a type II hypersensitivity Autoantibodies bind to RBC antigens causing extra- or intravascular hemolysis Spherocytes & agglutination are evidence of immune-mediated RBC destruction Hyperbilirubinemia/bilirubinuria & hemolyzed serum/hemoglobinuria/ghost cells are evidence of extra- and intravascular hemolysis, respectively Immune-mediated diseases can be associated with some drugs, vaccines, infection, or cancer  Dahlia 4-year-old FS Cavelier Spaniel Regurgitating water after drinking Difficulty walking No medications or vaccinations in the previous month  Dahlia 4-year-old FS Cavelier Spaniel Fatigable palpebral and withdrawal reflexes Megaesophagus on thoracic radiographs Acetylcholine receptor antibody titers (AChRab): 5.34mmol/L (normal