Peripheral blood lymphocyte subtypes in dogs with different stages of myxomatous mitral valve disease

Abstract

Background Data on alterations in peripheral blood lymphocyte (PBL) subtypes in dogs with myxomatous mitral valve disease (MMVD) is lacking. Objectives To investigate PBL subtypes and their correlation with parameters of inflammation and MMVD progression markers in dogs with different stages of MMVD. Animals Seventy‐eight client‐owned dogs: 65 with MMVD (American College of Veterinary Internal Medicine [ACVIM] classification stages B2, C, and D) and 13 healthy controls. Methods Prospective cross‐sectional study. Complete cardiac assessment, flow cytometry (T lymphocytes [CD3+], their subtypes [CD3+CD4+, CD3+CD8+, CD3+CD4+CD8+, CD3+CD4−CD8−], and B lymphocytes [CD45+CD21+]) and measurement of N‐terminal pro B‐type natriuretic peptide, cardiac troponin I, and C‐reactive protein concentrations were performed. Results The percentage of CD3+CD4+ lymphocytes was significantly lower in stable ACVIM C patients (P = .01) and unstable ACVIM C and D patients (P = .003), the percentage of CD3+CD8+ lymphocytes was significantly higher in stable ACVIM C patients (P = .01) and unstable ACVIM C and D patients (P = .01), CD3+CD8+ lymphocyte concentration was significantly higher in unstable ACVIM C and D patients (P = .05), and the CD3+CD4+/CD3+CD8+ ratio was significantly lower in stable ACVIM C patients (P = .01) and unstable ACVIM C and D patients (P = .01) compared with healthy controls. Conclusions and Clinical Importance The percentages of CD3+CD4+ and CD3+CD8+ PBL and CD4+/CD8+ ratio were altered in MMVD dogs with congestive heart failure (ACVIM C, D), but not in ACVIM B2, suggesting involvement of these PBL subtypes in the pathogenesis of congestive heart failure in dogs with MMVD.

Effects of Coenzyme Q10 Supplementation on Oxidative Stress Markers, Inflammatory Markers, Lymphocyte Subpopulations, and Clinical Status in Dogs with Myxomatous Mitral Valve Disease

“…Lymphocyte subpopulations were not affected by CoQ 10 supplementation in our study. The differences in lymphocyte subtypes previously described in dogs with CHF in comparison to healthy dogs [ 38 , 39 ] were also not observed in the present cohort of dogs, possibly because most dogs included in this study were in stable CHF and none were critically ill, whereas many critically ill patients were included in our previous cross-section study [ 39 ]. However, we found a significantly lower T helper percentage and CD4/CD8 ratio and a significantly higher percentage of cytotoxic T lymphocytes in ACVIM B2 patients compared with CHF patients and healthy dogs, which we believe may be because the group included the oldest participants or due to advanced cardiac remodeling in this group.…”

“…A higher neutrophil percentage has been found in dogs with advanced-stage CHF in comparison to dogs with stable CHF and/or non-CHF dogs or healthy controls [ 29 , 30 , 47 ]. Low lymphocyte counts are often found in human CVD and were shown to be a predictor of mortality in CVD patients [ 48 , 49 , 50 ], but the results of studies in dogs are contradictory, with most of them not detecting decreased lymphocyte count or percentage in canine patients with heart disease [ 29 , 30 , 38 , 39 , 47 ]; however, in one of the mentioned studies, a significantly lower lymphocyte percentage was found in CHF and non-CHF groups of canine cardiac patients compared to that in healthy dogs [ 30 ]. In another study, a lower lymphocyte count was shown in dogs with advanced-stage CHF in comparison to that in dogs with stable CHF and healthy controls [ 38 ].…”

“…Flow cytometric analysis of whole blood samples to determine the percentage of lymphocyte subpopulations, including T lymphocytes (CD3+), T helper cells (CD3+CD4+), activated T helper cells (CD3+CD4+CD25+), cytotoxic T lymphocytes (CD3+CD8+), activated cytotoxic T lymphocytes (CD3+CD8+CD25+), double-positive T lymphocytes (DPT) (CD3+CD4+CD8+), double-negative T lymphocytes (DNT) (CD3+CD4-CD8-), and B lymphocytes (CD45+CD21+), was performed as described previously [ 39 ]. Briefly, the whole-blood lysis method was used according to the manufacturer’s protocol [ 43 ].…”

“…Besides markers of inflammation, lymphocyte subpopulations have also been reported to be altered in both people with HF [ 36 , 37 ] and dogs with cardiac diseases, including MMVD and CHF [ 38 , 39 ]. In a study of dogs with MMVD conducted by our group [ 39 ], a lower percentage of T helper lymphocytes, a higher percentage of cytotoxic T lymphocytes, and a lower T helper/cytotoxic T lymphocyte ratio were documented in dogs with CHF due to MMVD compared to healthy controls, whereas these alterations were not present in the non-CHF group of participating MMVD patients. As far as we know, the effect of CoQ 10 supplementation on lymphocyte subtypes has not been studied in dogs with heart diseases.…”

Prognostic Efficacy of Complete Blood Count Indices for Assessing the Presence and the Progression of Myxomatous Mitral Valve Disease in Dogs

“…Recently, in veterinary medicine, the efficacy of the NLR as a prognostic factor has been demonstrated in cats with hypertrophic cardiomyopathy [ 16 ]. Although leukocyte and platelet parameters have been investigated in dogs with inflammatory or neoplastic diseases [ 17 , 18 , 19 ], there have only been a few studies in dogs with spontaneous cardiac disease [ 20 , 21 ], and little is known about their relationships with conventional heart failure biomarkers and echocardiographic variables [ 22 ]. Furthermore, while CBC indices such as NLR, MLR, and PLR have been demonstrated to be potential biomarkers of the inflammatory response in inflammatory diseases, such as sepsis or pancreatitis and neoplastic diseases, such as oropharyngeal tumors in dogs [ 17 , 23 ], their evaluation in cardiac diseases has rarely been reported.…”