Major Histocompatibility Complex I and II Expression and Lymphocytic Subtypes in Muscle of Horses with Immune-Mediated Myositis.
Abstract: Major histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune-mediated myositis (IMM) of humans and dogs and in dysferlin-deficient muscular dystrophy. Objective: To determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM. Methods: Twenty-one IMM horses of Quarter Horse-related breeds, 3 healthy and 6 disease controls (3 pasture myopathy, 3 amylase-resistant polysaccharide storage myopathy [PSSM]). Methods: Immunohistochemical staining for MHC I, II, and CD4+, CD8+, CD20+ lymphocytes was performed on archived muscle of IMM and control horses. Scores were given for MHC I, II, and lymphocytic subtypes. Immunofluorescent staining for dysferlin, dystrophin, and a-sarcoglycan was performed. Results: Sarcolemmal MHC I and II expression was detected in 17/21 and 15/21 of IMM horses, respectively, and in specific fibers of PSSM horses, but not healthy or pasture myopathy controls. The CD4+, CD8+, and CD20+ cells were present in 20/21 IMM muscles with CD4+ predominance in 10/21 and CD8+ predominance in 6/21 of IMM horses. Dysferlin, dystrophin, and a-sarcoglycan staining were similar in IMM and control muscles. Conclusions: Deficiencies of dysferlin, dystrophin, and a-sarcoglycan are not associated with IMM. Sarcolemmal MHC I and II expression in a proportion of myofibers of IMM horses in conjunction with lymphocytic infiltration supports an immune-mediated etiology for IMM. The MHC expression also occured in specific myofibers in PSSM horses in the absence of lymphocytic infiltrates.
Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Publication Date: 2016-06-28 PubMed ID: 27352021PubMed Central: PMC5094553DOI: 10.1111/jvim.14371Google Scholar: Lookup
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- Journal Article
- B cells
- Clinical Pathology
- Disease Etiology
- Equine Diseases
- Equine Health
- Horses
- Immune Response
- Immune System
- Immunohistochemistry
- Immunology
- Inflammatory Response
- Lymphocytes
- Major Histocompatibility Complex (MHC)
- Muscle
- Polysaccharide Storage Myopathy
- T Cells
- Veterinary Medicine
- Veterinary Research
- White Blood Cells
Summary
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The research examines the expression levels of the Major Histocompatibility Complex (MHC) I and II in the muscle tissues of horses suffering from immune-mediated myositis (IMM), a condition where the body’s immune system mistakenly attacks healthy muscle tissue. The study also investigates any potential correlation between MHC expression, specific types of lymphocytes and the muscle protective protein, dysferlin.
Research Objective
The research has a threefold objective.
- First, it aims to determine if sarcolemmal MHC, a type of protein usually found on cell surfaces, is expressed in horses experiencing an active IMM episode.
- Second, the researchers wanted to check whether MHC expression is associated with a particular subtype of lymphocytes, a type of immune cell.
- Finally, the research seeks to ascertain if dysferlin, a muscle-protective protein, is expressed in IMM cases.
Methods
The study comprised of 21 IMM horses from Quarter Horse-related breeds, as well as 9 control horses (3 healthy, 3 with pasture myopathy, and 3 with polysaccharide storage myopathy [PSSM]). The researchers performed immunohistochemical staining on the archived muscle samples of these horses to determine the presence and levels of MHC I, II, and the lymphocyte subtypes CD4+, CD8+, and CD20+. Immunofluorescent staining was also done for proteins dysferlin, dystrophin, and a-sarcoglycan.
Findings
The researchers detected the expression of Sarcolemmal MHC I and II in the majority (17 out of 21 and 15 out of 21, respectively) of the IMM horses and in specific muscle fibers of PSSM horses, though such expressions weren’t found in healthy or pasture myopathy control horses. The lymphocyte subtypes were present in almost all IMM muscles, with CD4+ being predominant in 10 out of 21 cases, and CD8+ in 6 out of 21 cases. Meanwhile, the staining for dysferlin, dystrophin, and a-sarcoglycan was noted to be similar in both IMM cases and control horses.
Conclusions
The research concluded that there is no link between the deficiency of muscle-protective proteins dysferlin, dystrophin, and a-sarcoglycan with IMM. The presence of Sarcolemmal MHC I and II expression in muscle fibers of IMM horses, along with lymphocytic infiltration, supports the understanding that IMM is caused by an immune response. The expression of MHC was also found in specific muscle fibers of PSSM horses, even without noticeable lymphocytic infiltrates.
Cite This Article
APA
Durward-Akhurst SA, Finno CJ, Barnes N, Shivers J, Guo LT, Shelton GD, Valberg SJ.
(2016).
Major Histocompatibility Complex I and II Expression and Lymphocytic Subtypes in Muscle of Horses with Immune-Mediated Myositis.
J Vet Intern Med, 30(4), 1313-1321.
https://doi.org/10.1111/jvim.14371 Publication
Researcher Affiliations
- Department of Veterinary Population Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN.
- Department of Population Health and Reproduction, University of California-Davis, Davis, CA.
- Department of Veterinary Population Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN.
- Department of Veterinary Population Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN.
- Department of Pathology, University of California, San Diego, La Jolla, CA.
- Department of Pathology, University of California, San Diego, La Jolla, CA.
- Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI.
MeSH Terms
- Animals
- Gene Expression Regulation
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Lymphocyte Subsets
- Major Histocompatibility Complex / genetics
- Major Histocompatibility Complex / physiology
- Muscle, Skeletal / cytology
- Muscle, Skeletal / metabolism
- Muscle, Skeletal / pathology
- Myositis / immunology
- Myositis / pathology
- Myositis / veterinary
Grant Funding
- K01 OD015134 / NIH HHS
- L40 TR001136 / NCATS NIH HHS
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Citations
This article has been cited 6 times.- Ochala J, Finno CJ, Valberg SJ. Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, MYH1(E321G).. Cells 2021 Dec 6;10(12).
- Gianino GM, Valberg SJ, Perumbakkam S, Henry ML, Gardner K, Penedo C, Finno CJ. Prevalence of the E321G MYH1 variant for immune-mediated myositis and nonexertional rhabdomyolysis in performance subgroups of American Quarter Horses.. J Vet Intern Med 2019 Mar;33(2):897-901.
- Valberg SJ, Henry ML, Perumbakkam S, Gardner KL, Finno CJ. An E321G MYH1 mutation is strongly associated with nonexertional rhabdomyolysis in Quarter Horses.. J Vet Intern Med 2018 Sep;32(5):1718-1725.
- Finno CJ, Gianino G, Perumbakkam S, Williams ZJ, Bordbari MH, Gardner KL, Burns E, Peng S, Durward-Akhurst SA, Valberg SJ. A missense mutation in MYH1 is associated with susceptibility to immune-mediated myositis in Quarter Horses.. Skelet Muscle 2018 Mar 6;8(1):7.
- Boyle AG, Timoney JF, Newton JR, Hines MT, Waller AS, Buchanan BR. Streptococcus equi Infections in Horses: Guidelines for Treatment, Control, and Prevention of Strangles-Revised Consensus Statement.. J Vet Intern Med 2018 Mar;32(2):633-647.
- Hunyadi L, Sundman EA, Kass PH, Williams DC, Aleman M. Clinical Implications and Hospital Outcome of Immune-Mediated Myositis in Horses.. J Vet Intern Med 2017 Jan;31(1):170-175.
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