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Polyclonal B‐cell lymphocytosis in English bulldogs

BACKGROUND: English bulldogs disproportionally develop an expansion of small B‐cells, which has been interpreted as B‐cell chronic lymphocytic leukemia (BCLL). However, clonality testing in these cases has often not been supportive of neoplasia. HYPOTHESIS: English bulldogs have a syndrome of nonneo...

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Autores principales: Rout, Emily D., Moore, A Russell, Burnett, Robert C., Labadie, Julia D., Hughes, Kelly L., Navin, Paul A., Yoshimoto, Janna A., Avery, Paul R., Avery, Anne C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694837/
https://www.ncbi.nlm.nih.gov/pubmed/33058280
http://dx.doi.org/10.1111/jvim.15913
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author Rout, Emily D.
Moore, A Russell
Burnett, Robert C.
Labadie, Julia D.
Hughes, Kelly L.
Navin, Paul A.
Yoshimoto, Janna A.
Avery, Paul R.
Avery, Anne C.
author_facet Rout, Emily D.
Moore, A Russell
Burnett, Robert C.
Labadie, Julia D.
Hughes, Kelly L.
Navin, Paul A.
Yoshimoto, Janna A.
Avery, Paul R.
Avery, Anne C.
author_sort Rout, Emily D.
collection PubMed
description BACKGROUND: English bulldogs disproportionally develop an expansion of small B‐cells, which has been interpreted as B‐cell chronic lymphocytic leukemia (BCLL). However, clonality testing in these cases has often not been supportive of neoplasia. HYPOTHESIS: English bulldogs have a syndrome of nonneoplastic B‐cell expansion. ANIMALS: Eighty‐four English bulldogs with small‐sized CD21+ B‐cell lymphocytosis in the blood as determined by flow cytometry. METHODS: This is a retrospective study. We characterized this syndrome by assessing B‐cell clonality, clinical presentation, flow cytometric features, and immunoglobulin gammopathy patterns. We identified 84 cases with CD21+ lymphocytosis among 195 English bulldogs with blood samples submitted to the Colorado State University‐Clinical Immunology laboratory for immunophenotyping between 2010 and 2019. Flow cytometry features were compared to normal B‐cells and BCLL cases. PCR for antigen receptor rearrangements (PARR) by multiple immunoglobulin primers was performed to assess B‐cell clonality. A subset of cases with gammopathy were examined by protein electrophoresis, immunofixation, and immunoglobulin subclass ELISA quantification. RESULTS: Seventy percent (58/83) of cases had polyclonal or restricted polyclonal immunoglobulin gene rearrangements, suggesting nonmalignant B‐cell expansion. The median age of all dogs in the study was 6.8 years and 74% were male. The median (range) lymphocyte count was 22 400/μL (2000‐384 400/μL) and B‐cells had low expression of class II MHC and CD25. Splenomegaly or splenic masses were detected in 57% (26/46) of cases and lymphadenopathy in 11% (7/61). Seventy‐one percent (52/73) of cases had hyperglobulinemia and 77% (23/30) with globulin characterization had IgA ± IgM polyclonal or restricted polyclonal gammopathy patterns. CONCLUSIONS AND CLINICAL IMPORTANCE: Polyclonal B‐cell lymphocytosis in English bulldogs is characterized by low B‐cell class II MHC and CD25 expression, splenomegaly and hyperglobulinemia consisting of increased IgA ± IgM. We hypothesize that this syndrome has a genetic basis.
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spelling pubmed-76948372020-12-07 Polyclonal B‐cell lymphocytosis in English bulldogs Rout, Emily D. Moore, A Russell Burnett, Robert C. Labadie, Julia D. Hughes, Kelly L. Navin, Paul A. Yoshimoto, Janna A. Avery, Paul R. Avery, Anne C. J Vet Intern Med SMALL ANIMAL BACKGROUND: English bulldogs disproportionally develop an expansion of small B‐cells, which has been interpreted as B‐cell chronic lymphocytic leukemia (BCLL). However, clonality testing in these cases has often not been supportive of neoplasia. HYPOTHESIS: English bulldogs have a syndrome of nonneoplastic B‐cell expansion. ANIMALS: Eighty‐four English bulldogs with small‐sized CD21+ B‐cell lymphocytosis in the blood as determined by flow cytometry. METHODS: This is a retrospective study. We characterized this syndrome by assessing B‐cell clonality, clinical presentation, flow cytometric features, and immunoglobulin gammopathy patterns. We identified 84 cases with CD21+ lymphocytosis among 195 English bulldogs with blood samples submitted to the Colorado State University‐Clinical Immunology laboratory for immunophenotyping between 2010 and 2019. Flow cytometry features were compared to normal B‐cells and BCLL cases. PCR for antigen receptor rearrangements (PARR) by multiple immunoglobulin primers was performed to assess B‐cell clonality. A subset of cases with gammopathy were examined by protein electrophoresis, immunofixation, and immunoglobulin subclass ELISA quantification. RESULTS: Seventy percent (58/83) of cases had polyclonal or restricted polyclonal immunoglobulin gene rearrangements, suggesting nonmalignant B‐cell expansion. The median age of all dogs in the study was 6.8 years and 74% were male. The median (range) lymphocyte count was 22 400/μL (2000‐384 400/μL) and B‐cells had low expression of class II MHC and CD25. Splenomegaly or splenic masses were detected in 57% (26/46) of cases and lymphadenopathy in 11% (7/61). Seventy‐one percent (52/73) of cases had hyperglobulinemia and 77% (23/30) with globulin characterization had IgA ± IgM polyclonal or restricted polyclonal gammopathy patterns. CONCLUSIONS AND CLINICAL IMPORTANCE: Polyclonal B‐cell lymphocytosis in English bulldogs is characterized by low B‐cell class II MHC and CD25 expression, splenomegaly and hyperglobulinemia consisting of increased IgA ± IgM. We hypothesize that this syndrome has a genetic basis. John Wiley & Sons, Inc. 2020-10-15 2020 /pmc/articles/PMC7694837/ /pubmed/33058280 http://dx.doi.org/10.1111/jvim.15913 Text en © 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle SMALL ANIMAL
Rout, Emily D.
Moore, A Russell
Burnett, Robert C.
Labadie, Julia D.
Hughes, Kelly L.
Navin, Paul A.
Yoshimoto, Janna A.
Avery, Paul R.
Avery, Anne C.
Polyclonal B‐cell lymphocytosis in English bulldogs
title Polyclonal B‐cell lymphocytosis in English bulldogs
title_full Polyclonal B‐cell lymphocytosis in English bulldogs
title_fullStr Polyclonal B‐cell lymphocytosis in English bulldogs
title_full_unstemmed Polyclonal B‐cell lymphocytosis in English bulldogs
title_short Polyclonal B‐cell lymphocytosis in English bulldogs
title_sort polyclonal b‐cell lymphocytosis in english bulldogs
topic SMALL ANIMAL
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694837/
https://www.ncbi.nlm.nih.gov/pubmed/33058280
http://dx.doi.org/10.1111/jvim.15913
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