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INTRODUCTION: Chronic kidney disease (CKD) poses a significant global health burden, with increasing prevalence and high morbidity and mortality rates, particularly in end-stage kidney disease (ESKD). While traditional risk factors contribute, the exact mechanisms remain elusive, with inflammation playing a pivotal role. Medium cut-off (MCO) membranes offer promise in improving dialysis outcomes by efficiently clearing uremic toxins without substantial albumin loss. We aimed to elucidate the impact of MCO and high-flux (HF) membranes on peripheral blood lymphocyte subpopulations in hemodialysis patients. METHODS: Twenty-four ESKD patients underwent 36 sessions each with MCO and HF membranes. Immunophenotyping by flow cytometry was performed to analyze lymphocyte subsets. RESULTS: NK cell percentages significantly increased with MCO, returning to baseline with HF. Th1 cells decreased post-HF, while Th2 and TFH cells increased with MCO and persisted. Treg cells remained stable with MCO but decreased with HF. CONCLUSION: MCO dialysis induced an anti-inflammatory shift, evidenced by increased Th2 and TFH cells and stable Treg cells. NK cells also responded favorably to MCO. These findings underscore MCO membranes' potential to modulate immune responses and improve patient outcomes in ESKD.
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INTRODUCTION: Antibodies to cell surface proteins of astrocytes have been described in chronic inflammatory demyelinating disorders (CIDD) of the central nervous system including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Our aim was to identify novel anti-astrocyte autoantibodies in relapsing remitting MS (RRMS) patients presenting predominantly with spinal cord and optic nerve attacks (MS-SCON). METHODS: Sera of 29 MS-SCON patients and 36 healthy controls were screened with indirect immunofluorescence to identify IgG reacting with human astrocyte cultures. Putative target autoantigens were investigated with immunoprecipitation (IP) and liquid chromatography-mass/mass spectrometry (LC-MS/MS) studies using cultured human astrocytes. Validation of LC-MS/MS results was carried out by IP and ELISA. RESULTS: Antibodies to astrocytic cell surface antigens were detected in 5 MS-SCON patients by immunocytochemistry. LC-MS/MS analysis identified chloride intracellular channel protein-1 (CLIC1) as the single common membrane antigen in 2 patients with MS-SCON. IP experiments performed with the commercial CLIC1 antibody confirmed CLIC1-antibody. Home made ELISA using recombinant CLIC1 protein as the target antigen identified CLIC1 antibodies in 9/29 MS-SCON and 3/15 relapsing inflammatory optic neuritis (RION) patients but in none of the 30 NMOSD patients, 36 RRMS patients with only one or no myelitis/optic neuritis attacks and 36 healthy controls. Patients with CLIC1-antibodies showed trends towards exhibiting reduced disability scores. CONCLUSION: CLIC1-antibody was identified for the first time in MS and RION patients, confirming once again anti-astrocytic autoimmunity in CIDD. CLIC1-antibody may potentially be utilized as a diagnostic biomarker for differentiation of MS from NMOSD.
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BACKGROUND: West Syndrome (WS) is an epileptic encephalopathy that typically occurs in infants and is characterized by hypsarrhythmia, infantile spasms, and neurodevelopmental impairment. Demonstration of autoantibodies and cytokines in some WS patients and favorable response to immunotherapy have implicated inflammation as a putative trigger of epileptiform activity in WS. Our aim was to provide additional support for altered inflammatory responses in WS through peripheral blood immunophenotype analysis. METHODS: Eight WS cases treated with synacthen and 11 age- and sex-matched healthy volunteers were included. Peripheral blood mononuclear cells (PBMC) were isolated and immunophenotyping was performed in pre-treatment baseline (8 patients) and 3 months post-treatment (6 patients) samples. The analysis included PBMC expressing NFκB transcription and NLRP3 inflammasome factors. RESULTS: In pre-treatment baseline samples, switched memory B cells (CD19+IgD-CD27+) were significantly reduced, whereas plasma cells (CD19+CD38+CD138+) and cytotoxic T cells (CD3+CD8+) were significantly increased. Regulatory T and B cell ratios were not significantly altered. Synacthen treatment only marginally reduced helper T cell ratios and did not significantly change other T, B, NK and NKT cell and monocyte ratios. CONCLUSIONS: Our findings lend further support for the involvement of inflammation-related mechanisms in WS. New-onset WS patients are inclined to display increased plasma cells in the peripheral blood. Synacthen treatment does not show a beneficial effect on most effector acquired and innate immunity subsets.