Equine common variable immunodeficiency: lessons from 100 clinical cases.
Abstract: The clinical manifestation of recurrent fevers and infections alerts the clinician to the possibility of an underlying immunodeficiency. Common variable immunodeficiency (CVID) in the horse is a rare late-onset, non-familial immunologic disorder of B cell depletion and/or dysfunction with resultant inadequate antibody production. The most common clinical presentations in horses with CVID are recurrent upper and/or lower respiratory infections, meningitis and/or ataxia, cholangiohepatitis, infectious colitis, infectious dermatitis, and severe gastrointestinal parasitism. Immune-mediated and lymphoproliferative conditions are additional clinical features. The diagnosis of CVID in horses is based on persistent hypogammaglobulinemia primarily caused by a serum IgG concentration below 10.00 g/L in at least 2 different measurements, often accompanied by a serum IgM concentration below 0.50 g/L. Most horses with CVID show a persistent peripheral blood B cell distribution below 6% of total circulating lymphocytes, indicating severe B cell paucity or depletion, but the B cell distribution can be within the normal reference interval. Post-mortem findings add diagnostic information about the distribution of B and T cells in lymphoid tissues. Clinical management of horses with immunodeficiency is intense and expensive, and these factors weigh on the difficult decision of elective euthanasia. To date, no genetic mutation has been identified in horse patients with CVID, and the large number of breeds of single-affected individuals in a same herd or immediate lineage from various parts of the U.S. and the world do not point at an obvious inheritable mechanism of disease or environmental risk factors. This article describes the clinical and immunological findings in 100 cases, and comparisons with the disease in human patients.
Publication Date: 2024-01-31 PubMed ID: 39555145PubMed Central: PMC11565712DOI: 10.1111/eve.13948Google Scholar: Lookup
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- Journal Article
Summary
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The article examines the symptoms, diagnosis, and treatment of Common Variable Immunodeficiency (CVID) in horses. This rare disorder in horses impacts the B cells and can lead to recurrent infections and other clinical conditions due to inadequate antibody production.
Clinical Manifestation
- The common signs of CVID in horses include recurring instances of respiratory infections, meningitis, ataxia (loss of control over bodily movements), cholangiohepatitis (inflammation of the liver and bile ducts), infectious dermatitis (skin inflammation), and severe gastrointestinal parasitism.
- Some horses with CVID also present with immune-mediated and lymphoproliferative conditions.
Diagnosis
- Diagnosis of CVID in horses is generally based on persistent hypogammaglobulinemia, primarily caused by serum IgG concentration below 10.00 g/L in at least two different measurements, often accompanied by a serum IgM concentration below 0.50 g/L.
- Most CVID-afflicted horses show peripheral blood B cell distribution below 6% of total circulating lymphocytes, indicating severe B cell paucity or depletion. However, B cell distribution can be within the normal range.
- Post-mortem analysis can also provide crucial information about the distribution of B and T cells in lymphoid tissues.
Treatment and Management
- The clinical management of horses with CVID is intense and expensive.
- Due to the associated costs and medical intensity, decisions such as elective euthanasia can be difficult.
Genetic Factors
- Despite thorough investigations, no genetic mutation has been identified in horses with CVID.
- The widespread representation of the disease across various breeds and geographical locations does not indicate an obvious hereditary transmission or environmental risk factors.
The study presents findings from 100 clinical cases of equine CVID and compares them to similar cases in human patients to expand the understanding of the disease.
Cite This Article
APA
Julia M, Felippe B.
(2024).
Equine common variable immunodeficiency: lessons from 100 clinical cases.
Equine Vet Educ, 36(10), 543-554.
https://doi.org/10.1111/eve.13948 Publication
Researcher Affiliations
- Equine Immunology Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
- Equine Immunology Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Grant Funding
- DP2 OD007216 / NIH HHS
Conflict of Interest Statement
Conflict of interest statement M.J.B. Felippe is the head of the Equine Immunology Laboratory, a not-for-profit research laboratory that provides immunologic testing for horses with suspected immunodeficiencies.
References
This article includes 48 references
- Agarwal S, Cunningham-Rundles C. Assessment and clinical interpretation of reduced IgG values. Annals of Allergy, Asthma & Immunology 99, 281–283.
- Agarwal S, Cunningham-Rundles C. Autoimmunity in common variable immunodeficiency. Annals of Allergy, Asthma & Immunology 123, 454–460.
- Amaya-Uribe L, Rojas M, Azizi G, Anaya JM, Gershwin ME. Primary immunodeficiency and autoimmunity: A comprehensive review. Journal of Autoimmunity 99, 52–72.
- Ameratunga R, Woon ST, Gillis D, Koopmans W, Steele R. New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clinical and Experimental Immunology 174, 203–211.
- Ameratunga R, Woon ST. Perspective: Evolving Concepts in the Diagnosis and Understanding of Common Variable Immunodeficiency Disorders (CVID). Clinical Reviews in Allergy & Immunology 59, 109–121.
- Azizi G, Rezaei N, Kiaee F, Tavakolinia N, Yazdani R, Mirshafiey A, Aghamohammadi A. T-Cell Abnormalities in Common Variable Immunodeficiency. Journal of Investigational Allergology and Clinical Immunology 26, 233–243.
- Barneda-Zahonero B, Roman-Gonzalez L, Collazo O, Mahmoudi T, Parra M. Epigenetic regulation of B lymphocyte differentiation, transdifferentiation, and reprogramming. Comparative and Functional Genomics 2012:564381.
- Bogaert DJ, Dullaers M, Lambrecht BN, Vermaelen KY, De Baere E, Haerynck F. Genes associated with common variable immunodeficiency: one diagnosis to rule them all?. Journal of Medical Genetics 53, 575–590.
- Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, Espinosa-Rosales FJ, Hammarström L, Nonoyama S, Quinti I, Routes JM, Tang ML, Warnatz K. International Consensus Document (ICON): Common Variable Immunodeficiency Disorders. Journal of Allergy and Clinical Immunology: In Practice 4, 38–59.
- Davis WC, Heirman LR, Hamilton MJ, Parish SM, Barrington GM, Loftis A, Rogers M. Flow cytometric analysis of an immunodeficiency disorder affecting juvenile llamas. Veterinary Immunology and Immunopathology 74, 103–120.
- Day MJ, Power C, Oleshko J, Rose M. Low serum immuno- globulin concentrations in related Weimaraner dogs. The Journal of small animal practice 38, 311–315.
- Foale RD, Herrtage ME, Day MJ. Retrospective study of 25 young weimaraners with low serum immunoglobulin concentrations and inflammatory disease. Veterinary Record 153, 553–558.
- Fischer U, Yang JJ, Ikawa T, Hein D, Vicente-Dueñas C, Borkhardt A, Sánchez-García I. Cell Fate Decisions: The Role of Transcription Factors in Early B-cell Development and Leukemia. Blood Cancer Discovery 1, 224–233.
- Flaminio MJ, Rush BR, Shuman W. Peripheral blood lymphocyte subpopulations and immunoglobulin concentrations in healthy foals and foals with Rhodococcus equi pneumonia. Journal of Veterinary Internal Medicine 13, 206–212.
- Flaminio MJ, Rush BR, Davis EG, Hennessy K, Shuman W, Wilkerson MJ. Characterization of peripheral blood and pulmonary leukocyte function in healthy foals. Veterinary Immunology and Immunotherapy 73, 267–285.
- Flaminio MJ, LaCombe V, Kohn CW, Antczak DF. Common variable immunodeficiency in a horse. Journal of the American Veterinary Medical Association 221, 1296–1267.
- Flaminio MJ, Tallmadge RL, Salles-Gomes CO, Matychak MB. Common variable immunodeficiency in horses is characterized by B cell depletion in primary and secondary lymphoid tissues. Journal of Clinical Immunology 29, 107–116.
- Friedmann D, Goldacker S, Peter HH, Warnatz K. Preserved Cellular Immunity Upon Influenza Vaccination in Most Patients with Common Variable Immunodeficiency. Journal of Allergy and Clinical Immunology 8, 2332–2340.e5.
- Fox-Clipsham LY, Carter SD, Goodhead I, Hall N, Knottenbelt DC, May PD, Ollier WE, Swinburne JE. Identification of a mutation associated with fatal Foal Immunodeficiency Syndrome in the Fell and Dales pony. PLoS Genetics 7, e1002133.
- Hutchison JM, Garry FB, Johnson LW, Quackenbush SL, Getzy DM, Jensen WA, Hoover EA. Immunodeficiency syndrome associated with wasting and opportunistic infection in juvenile llamas: 12 cases (1988–1990). Journal of the American Veterinary Medical Association 201, 1070–1076.
- Hutchison JM, Garry F. Ill thrift and juvenile llama immunodeficiency syndrome. Veterinary Clinics of North America: Food Animal Practice 10, 331–343.
- Hutchison JM, Garry FB, Belknap EB, Getzy DM, Johnson LW, Ellis RP, Quackenbush SL, Rovnak J, Hoover EA, Cockerell GL. Prospective characterization of the clinicopathologic and immunologic features of an immunodeficiency syndrome affecting juvenile llamas. Veterinary Immunology and Immunopathology 49, 209–227.
- Kanemoto H, Morikawa R, Chambers JK, Kasahara K, Hanafusa Y, Uchida K, Ohno K, Nakayama H. Common variable immune deficiency in a Pomeranian with Pneumocystis carinii pneumonia. Journal of Veterinary Medicine Science 77, 715–719.
- Kienzler AK, Hargreaves CE, Patel SY. The role of genomics in common variable immunodeficiency disorders. Clinical and Experimental Immunology 188(3), 326–332.
- Lobetti RG, Leisewitz AL, Spencer JA. Pneumocystis carinii in the miniature dachshund: case report and literature review. Journal of Small Animal Practice 37, 280–285.
- Lobetti R. Common variable immunodeficiency in miniature dachshunds affected with Pneumonocystis carinii pneumonia. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 12, 39–45.
- Miller AB, Loynachan AT, Bush HM, Hart KA, Barker VD, Campana-Emard AG, Grubbs ST, Adams AA. Effects of pituitary pars intermedia dysfunction and Prascend (pergolide tablets) treatment on endocrine and immune function in horses. Domestic Animal Endocrinology 74, 106531.
- Motta-Raymundo A, Rosmaninho P, Santos DF, Ferreira RD, Silva SP, Ferreira C, Sousa AE, Silva SL. Contribution of Helicobacter pylori to the Inflammatory Complications of Common Variable Immunodeficiency. Frontiers in Immunology 13, 834137.
- Pecoraro HL, Felippe MJB, Miller AD, Divers TJ, Simpson KW, Guyer KM, Duhamel GE. Neuroborreliosis in a horse with common variable immunodeficiency. Journal of Veterinary Diagnostic Investigation 31, 241–245.
- Pellegrini-Masini A, Bentz AI, Johns IC, Parsons CS, Beech J, Whitlock RH, Flaminio MJ. Common variable immunodeficiency in three horses with presumptive bacterial meningitis. Journal of the American Veterinary Medical Association 227, 114–187.
- Perryman LE, McGuire TC. Evaluation for immune system failures in horses and ponies. Journal of the American Veterinary Medical Association 176, 1374–1377.
- Petini M, Furlanello T, Danesi P, Zoia A. Nested-polymerase chain reaction detection of Pneumocystis carinii f. sp. canis in a suspected immunocompromised Cavalier King Charles spaniel with multiple infections. SAGE Open Medical Case Reports 7, 2050313X19841169.
- Prieto JMB, Tallmadge RL, Felippe MJB. Developmental expression of B cell molecules in equine lymphoid tissues. Veterinary Immunology and Immunotherapy 183, 60–71.
- Scholes SF, Holliman A, May PD, Holmes MA. A syndrome of anaemia, immunodeficiency and peripheral ganglionopathy in Fell pony foals. Veterinary Record 142, 128–134.
- Shearer WT, Fleisher TA, Buckley RH, Ballas Z, Ballow M, Blaese RM, Bonilla FA, Conley ME, Cunningham-Rundles C, Filipovich AH, Fuleihan R, Gelfand EW, Hernandez-Trujillo V, Holland SM, Hong R, Lederman HM, Malech HL, Miles S, Notarangelo LD, Winkelstein J. Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. Journal of Allergy and Clinical Immunology 133, 961–966.
- Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, Scheible R, Rusch S, Gasteiger LM, Grimbacher B, Mahlaoui N, Ehl S, ESID Registry Working Party and collaborators. The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity. Journal of Allergy and Clinical Immunology: In Practice 7, 1763–1770.
- Sigvardsson M. Molecular Regulation of Differentiation in Early B-Lymphocyte Development. International Journal of Molecular Sciences 19, 1928.
- Smith T, Cunningham-Rundles C. Primary B-cell immunodeficiencies. Human Immunology 80, 351–362.
- Studdert MJ. Primary, severe, combined immunodeficiency disease of Arabian foals. Australian Veterinary Journal 54, 411–417.
- Tallmadge RL, Such KA, Miller KC, Matychak MB, Felippe MJ. Expression of essential B cell development genes in horses with common variable immunodeficiency. Molecular Immunology 51, 169–176.
- Tallmadge RL, Shen L, Tseng CT, Miller SC, Barry J, Felippe MJ. Bone marrow transcriptome and epigenome profiles of equine common variable immunodeficiency patients unveil block of B lymphocyte differentiation. Clinical Immunology 160, 261–276.
- Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, Klein C, Morio T, Oksenhendler E, Picard C, Puel A, Puck J, Seppänen MRJ, Somech R, Su HC, Sullivan KE, Torgerson TR, Meyts I. Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. Journal of Clinical Immunology 42, 1473–1507.
- Tennent-Brown BS, Navas de Solis C, Foreman JH, Goetz TE, Fredrickson RL, Borst LB, Flaminio MJBF. Common variable immunodeficiency in a horse with chronic peritonitis. Equine Veterinary Education 22, 393–399.
- Shin EK, Perryman LE, Meek K. A kinase-negative mutation of DNA-PK(CS) in equine SCID results in defective coding and signal joint formation. Journal of Immunology 158, 3565–3569.
- Song J, Lleo A, Yang GX, Zhang W, Bowlus CL, Gershwin ME, Leung PSC. Common Variable Immunodeficiency and Liver Involvement. Clinical Reviews in Allergy & Immunology 55, 340–351.
- Wang LA, Abbott JK. Common variable immunodeficiency: Challenges for diagnosis. Journal of Immunological Methods 509, 113342.
- Wong GK, Huissoon AP. T-cell abnormalities in common variable immunodeficiency: the hidden defect. Journal of Clinical Pathology 69, 672–676.
- Yazdani R, Habibi S, Sharifi L, Azizi G, Abolhassani H, Olbrich P, Aghamohammadi A. Common Variable Immunodeficiency: Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis, Classification, and Management. Journal of Investigational Allergology and Clinical Immunology 30, 14–34.
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