Clustering of End Stage Renal Disease Patients by Dimensionality Reduction Algorithms According to Lymphocyte Senescence Markers

Abstract

End stage renal disease (ESRD) engenders detrimental effects in the Immune system, manifested as quantitative alterations of lymphocyte subpopulations, akin, albeit not identical to those observed during the ageing process. We performed dimensionality reduction of an extended lymphocyte phenotype panel of senescent and exhaustion related markers in ESRD patients and controls with Principal Component Analysis (PCA) and Uniform Manifold Approximation and Projection (UMAP). The plane defined by the first two principal components of PCA showed two fuzzy clusters, for patients and controls, respectively, with loadings of non-senescent markers pointing towards the controls’ centroid. Naive lymphocytes were reduced in ESRD patients compared to controls (CD4+CD45RA+CCR7+ 200(150-328) vs. 426(260-585cells/μl respectively, P = 0.001, CD19+IgD+CD27- 54(26-85) vs. 130(83-262)cells/μl respectively, P < 0.001). PCA projections of the multidimensional ESRD immune phenotype suggested a more senescent phenotype in hemodialysis compared to hemodiafiltration treated patients. Lastly, clustering based on UMAP revealed three distinct patient groups, exhibiting gradual changes for naive, senescent, and exhausted lymphocyte markers. Machine learning algorithms can distinguish ESRD patients from controls, based on their immune-phenotypes and also, unveil distinct immunological groups within patients’ cohort, determined possibly by dialysis prescription.

Different Types of Chronic Inflammation Engender Distinctive Immunosenescent Profiles in Affected Patients

“…To our knowledge, this is the first study which compares phenotypic alterations of B and T lymphocytes in two forms of systemic chronic inflammation. We have previously described the actual and unique consequences of chronic kidney disease on lymphocytes’ structure and function, resembling that of ageing, however, retaining substantial differences [ 11 , 12 , 13 ]. The detrimental effects of renal impairment on the immune function are attributed to uremia, uremic toxins, dialysis method per se, oxidative stress, and probably to other yet unrecognized causes [ 1 ].…”

“…Repetitive activation of T lymphocytes, in the presence of chronic inflammation and results in the gradual reduction leading to elimination of CD28 receptor, CD57 molecule is gradually expressed in mature T cell subtypes. [ 1 , 11 , 12 , 13 ].…”

“…The following monoclonal antibodies were used to characterize the phenotypes of B lymphocytes: CD45 PC7, CD19 PC5, IgD FIC, and CD27 ECD and those of T lymphocytes: CD45 PC7, CD3 FITC, CD4 Pacific Blue, CD8 PC5, CD45RA APC, CCR7 PE, CD28 ECD, CD57 FITC, CD31 ECD. Three different tubes were used for the assessment of T cell and one tube for B cell markers, and the subpopulations defined based on combination as has been described before [ 12 ].…”

“…The above lymphocyte modifications are similar to aging in some points; however, there are certain differences, probably attributed to distinct mechanisms. [ 1 , 11 , 12 , 13 ].…”

Two Cases of Autoimmune Thyroid Disorders after COVID Vaccination in Dialysis Patients

“…Alterations of adaptive immunity are prominent in these patients and resemble natural aging, albeit with distinct discrepancies present. Severe lymphopenia with a reduction mainly in naïve T and B cell subpopulations results in a less intense immune response and consequently delayed pathogen clearance [ 22 ]. Characteristically, the median time until clearance of SARS-CoV-2, even after clinical remission, was rather elongated in dialysis patients in comparison to patients without kidney disease [ 23 ].…”