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JPMA. the Journal of the Pakistan... Apr 2024To assess the association of serum protein electrophoresis abnormalities with clinicopathological characteristics, and its impact on overall survival in chronic...
OBJECTIVE
To assess the association of serum protein electrophoresis abnormalities with clinicopathological characteristics, and its impact on overall survival in chronic lymphocytic leukaemia patients.
METHODS
The prospective study was conducted at Haematology and Immunology departments of the University of Health Sciences, Lahore, Pakistan, from 2019 to 2022, and comprised newly diagnosed chronic lymphocytic leukaemia patients. Lactate dehydrogenase and beta-2 microglobulin levels were measured by spectrophotometric principle, whereas serum protein electrophoresis was determined through commercially available capillary electrophoresis systems. Patients were followed up for 2 years post-diagnosis. Data was analysed using SPSS 21.
RESULTS
Of the 50 patients, 40(80%) were males and 10(20%) were females. The overall mean age was 60±11 years. Serum protein electrophoresis was available for 40(80%) patients, and, among them, 12(30%) patients had abnormal levels, while 29(72.5%) required treatment. Overall response rate was 25(86.2%), and median two-year overall survival was 16.5 months (95% confidence interval: 10-20 months). Abnormal serum protein electrophoresis was significantly associated with Binet stage C, lower mean haemoglobin levels and higher median levels of lactate dehydrogenase and beta-2 microglobulin (p<0.05)). Regarding overall survival, the survival curves of chronic lymphocytic leukaemia patients with normal and abnormal serum protein electrophoresis status differed significantly (p=0.04).
CONCLUSION
Abnormal serum protein electrophoresis could be considered a surrogate marker for advanced chronic lymphocytic leukaemia disease.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Female; Male; Middle Aged; Prognosis; Aged; Prospective Studies; beta 2-Microglobulin; Blood Protein Electrophoresis; L-Lactate Dehydrogenase; Pakistan; Hemoglobins; Survival Rate; Neoplasm Staging; Blood Proteins
PubMed: 38751267
DOI: 10.47391/JPMA.10116 -
Cellular and Molecular Neurobiology May 2024Central nervous system (CNS) disorders represent the leading cause of disability and the second leading cause of death worldwide, and impose a substantial economic... (Review)
Review
Central nervous system (CNS) disorders represent the leading cause of disability and the second leading cause of death worldwide, and impose a substantial economic burden on society. In recent years, emerging evidence has found that beta2 -microglobulin (B2M), a subunit of major histocompatibility complex class I (MHC-I) molecules, plays a crucial role in the development and progression in certain CNS diseases. On the one hand, intracellular B2M was abnormally upregulated in brain tumors and regulated tumor microenvironments and progression. On the other hand, soluble B2M was also elevated and involved in pathological stages in CNS diseases. Targeted B2M therapy has shown promising outcomes in specific CNS diseases. In this review, we provide a comprehensive summary and discussion of recent advances in understanding the pathological processes involving B2M in CNS diseases (e.g., Alzheimer's disease, aging, stroke, HIV-related dementia, glioma, and primary central nervous system lymphoma).
Topics: Humans; beta 2-Microglobulin; Central Nervous System Diseases; Animals
PubMed: 38743119
DOI: 10.1007/s10571-024-01481-6 -
Kidney Research and Clinical Practice Mar 2024In Japan, pediatric urinary screening in schools for asymptomatic hematuria and proteinuria began in 1974 and has been very successful in detecting asymptomatic kidney...
In Japan, pediatric urinary screening in schools for asymptomatic hematuria and proteinuria began in 1974 and has been very successful in detecting asymptomatic kidney diseases at an early stage. While the American Academy of Pediatrics recommended discontinuing urinalysis as a public health service in 2007, urinary screening in Japan has proven extremely successful in reducing the incidence of kidney failure with replacement therapy in children and young adults, especially through the early treatment of glomerulonephritis, such as immunoglobulin A nephropathy. Furthermore, the positivity rate on urinary screening in Japan is significantly lower than in the United States where the rate of false positive results is typically very high. Japan's seamless and efficient pediatric urinary screening may be a helpful example for other countries as well. However, the present investigation revealed several, unresolved problems with the system. For example, the methods used varied in terms of their cutoff point, additional examinations, and types of detailed testing. In Japan, various urinary screening methods are being tested to optimize the system for national use. Recently, the authors also recommended a system of detailed examinations, including beta-2 microglobulin testing and ultrasonography, to detect congenital anomalies of the kidney and urinary tract, the most common, underlying disease in kidney failure with replacement therapy, which is often overlooked until the symptoms have become grave. While school urinary screening has been ongoing for about 50 years and should be continued, improvements should also be made to it as needed.
PubMed: 38738276
DOI: 10.23876/j.krcp.23.127 -
Scientific Reports May 2024Dialyzers are classified into five types based on their β-microglobulin clearance rate and albumin sieving coefficient: Ia, Ib, IIa, and IIb. In addition, a new...
Dialyzers are classified into five types based on their β-microglobulin clearance rate and albumin sieving coefficient: Ia, Ib, IIa, and IIb. In addition, a new classification system introduced a type S dialyzer. However, limited information is available regarding the impact of dialyzer type on patient outcomes. A cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry database. Total 181,804 patients on hemodialysis (HD) were included in the study, categorized into four groups (type Ia, IIa, IIb, and S). The associations between each group and two-year all-cause mortality were assessed using Cox proportional hazard models. Furthermore, propensity score-matching analysis was performed. By the end of 2019, 34,185 patients on dialysis had died. After adjusting for all confounders, the risk for all-cause mortality was significantly lower in the type IIa, and S groups than in the type Ia group. These significant findings were consistent after propensity score matching. In conclusion, our findings suggest that super high-flux dialyzers, with a β-microglobulin clearance of ≥ 70 mL/min, may be beneficial for patients on HD, regardless of their albumin sieving coefficient. In addition, type S dialyzers may be beneficial for elderly and malnourished patients on dialysis.Trial registration number: UMIN000018641.
Topics: Humans; Renal Dialysis; Japan; Female; Male; Aged; Middle Aged; beta 2-Microglobulin; Kidney Failure, Chronic; Proportional Hazards Models; Propensity Score; Cohort Studies; Risk Factors; Aged, 80 and over
PubMed: 38704419
DOI: 10.1038/s41598-024-60831-y -
Virology Jul 2024Porcine reproductive and respiratory syndrome virus (PRRSV) infection inhibits swine leukocyte antigen class I (SLA-I) expression in pigs, resulting in inefficient...
Porcine reproductive and respiratory syndrome virus (PRRSV) infection inhibits swine leukocyte antigen class I (SLA-I) expression in pigs, resulting in inefficient antigen presentation and subsequent low levels of cellular PRRSV-specific immunity as well as persistent viremia. We previously observed that the non-structural protein 4 (nsp4) of PRRSV contributed to inhibition of the β2-microglobulin (β2M) and SLA-I expression in cells. Here, we constructed a series of nsp4 mutants with different combination of amino acid mutations to attenuate the inhibitory effect of nsp4 on β2M and SLA-I expression. Almost all nsp4 mutants exogenously expressed in cells showed an attenuated effect on inhibition of β2M and SLA-I expression, but the recombinant PRRSV harboring these nsp4 mutants failed to be rescued with exception of the rPRRSV-nsp4-mut10 harboring three amino acid mutations. However, infection of rPRRSV-nsp4-mut10 not only enhanced β2M and SLA-I expression in both cells and pigs but also promoted the DCs to active the CD3CD8+T lymphocytes more efficiently, as compared with its parental PRRSV (rPRRVS-nsp4-wt). These data suggested that the inhibition of nsp4-mediated β2M downregulation improved β2M/SLA-I expression in pigs.
Topics: Porcine respiratory and reproductive syndrome virus; Animals; Swine; Porcine Reproductive and Respiratory Syndrome; Viral Nonstructural Proteins; Down-Regulation; beta 2-Microglobulin; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Cell Line; CD8-Positive T-Lymphocytes; Mutation
PubMed: 38696887
DOI: 10.1016/j.virol.2024.110083 -
Indian Journal of Nephrology 2024While the utility of beta-2 microglobulin (β2M) has been explored in various renal conditions to identify tubulointerstitial damage, it has not been adequately studied...
BACKGROUND
While the utility of beta-2 microglobulin (β2M) has been explored in various renal conditions to identify tubulointerstitial damage, it has not been adequately studied in nephrotic syndrome. The primary objective of the study was to compare urinary β2M levels in children with steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) in disease remission.
MATERIALS AND METHODS
This cross-sectional study was done at a tertiary care hospital between April 2019 and March 2020. Sixty children (2-18 years) with SSNS and SRNS (30 in each group) in remission were enrolled. SRNS patients were included after ≥1 year of treatment with calcineurin inhibitors (CNIs). Biochemical investigations were done to confirm remission; spot samples for urinary β2M were collected and estimation was done by an enzyme-linked immunosorbent assay (ELISA)-based kit.
RESULTS
Of the 60 children, 63% were boys. The median (interquartile range [IQR]) age at enrollment for SSNS and SRNS patients was 7 (4.1-9) and 11 (8.3-12) years, respectively. Urinary β2M levels were significantly higher in SRNS patients compared to SSNS patients (2.6 vs. 0.75 mg/ml, < 0.0001). Patients who received cyclosporine for >2 years had higher median urinary β2M levels compared to those who received it for a shorter period (2.63 vs. 1.83 mg/ml, = 0.03). Median β2M levels were higher in focal segmental glomerulosclerosis than minimal change disease (3.5 vs. 2.5 mg/ml).
CONCLUSION
Urinary β2M levels were higher in SRNS compared to SSNS disease in remission, and β2M levels correlated well with CNI use of >2 years. It appears to be a promising noninvasive tool to identify early tubular damage and progression in patients with nephrotic syndrome, especially SRNS.
PubMed: 38681018
DOI: 10.4103/ijn.ijn_339_22 -
Vaccines Apr 2024Ovarian cancer is one of the most common cancers among women and the most lethal malignancy of all gynecological cancers. Surgery is promising in the early stages;...
Ovarian cancer is one of the most common cancers among women and the most lethal malignancy of all gynecological cancers. Surgery is promising in the early stages; however, most patients are first diagnosed in the advanced stages, where treatment options are limited. Here, we present a 49-year-old patient who was first diagnosed with stage III ovarian cancer. After the tumor progressed several times under guideline therapies with no more treatment options available at that time, the patient received a fully individualized neoantigen-derived peptide vaccine in the setting of an individual healing attempt. The tumor was analyzed for somatic mutations via whole exome sequencing and potential neoepitopes were vaccinated over a period of 50 months. During vaccination, the patient additionally received anti-PD-1 therapy to prevent further disease progression. Vaccine-induced T-cell responses were detected using intracellular cytokine staining. After eleven days of in vitro expansion, four T-cell activation markers (namely IFN-ɣ, TNF-α, IL-2, and CD154) were measured. The proliferation capacity of neoantigen-specific T-cells was determined using a CFSE proliferation assay. Immune monitoring revealed a very strong CD4+ T-cell response against one of the vaccinated peptides. The vaccine-induced T-cells simultaneously expressed CD154, TNF, IL-2, and IFN-ɣ and showed a strong proliferation capacity upon neoantigen stimulation. Next-generation sequencing, as well as immunohistochemical analysis, revealed a loss of Beta-2 microglobulin (B2M), which is essential for MHC class I presentation. The results presented here implicate that the application of neoantigen-derived peptide vaccines might be considered for those cancer stages, where promising therapeutic options are lacking. Furthermore, we provide more data that endorse the intensive investigation of B2M loss as a tumor escape mechanism in clinical trials using anti-cancer vaccines together with immune-checkpoint inhibitors.
PubMed: 38675779
DOI: 10.3390/vaccines12040397 -
Biomolecules Apr 2024Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA () and...
Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA () and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-β-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). and nuclear DNA () were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b () gene, subunit 2 of NADH dehydrogenase (), and beta 2 microglobulin nuclear gene () were assessed by TaqMan assays. was defined as the ratio of the number of copies, through analysis of the and ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)-the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary , IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum , IL-10. BHI correlated directly with serum IL-10, and serum , and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with variations and inflammation from the early stages of diabetic kidney disease.
Topics: Humans; DNA, Mitochondrial; Male; Female; Diabetes Mellitus, Type 2; Middle Aged; Inflammation; Diabetic Nephropathies; Aged; Vascular Remodeling; Case-Control Studies
PubMed: 38672515
DOI: 10.3390/biom14040499 -
Kidney360 Apr 2024
Topics: Humans; Renal Dialysis; Sepsis; Catheter-Related Infections; Kidney Failure, Chronic
PubMed: 38662534
DOI: 10.34067/KID.0000000000000407 -
Renal Failure Dec 2024To delineate the efficacy and safety profile of hemodiafiltration with endogenous reinfusion (HFR) for uremic toxin removal in patients undergoing maintenance...
OBJECTIVE
To delineate the efficacy and safety profile of hemodiafiltration with endogenous reinfusion (HFR) for uremic toxin removal in patients undergoing maintenance hemodialysis (MHD).
METHODS
Patients who have been on MHD for a period of at least 3 months were enrolled. Each subject underwent one HFR and one hemodiafiltration (HDF) treatment. Blood samples were collected before and after a single HFR or HDF treatment to test uremic toxin levels and to calculate clearance rate. The primary efficacy endpoint was to compare uremic toxin levels of indoxyl sulfate (IS), λ-free light chains (λFLC), and β-microglobulin (β-MG) before and after HFR treatment. Secondary efficacy endpoints was to compare the levels of urea, interleukin-6 (IL-6), P-cresol, chitinase-3-like protein 1 (YKL-40), leptin (LEP), hippuric acid (HPA), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), fibroblast growth factor 23 (FGF23) before and after HFR treatment. The study also undertook a comparative analysis of uremic toxin clearance between a single HFR and HDF treatment. Meanwhile, the lever of serum albumin and branched-chain amino acids before and after a single HFR or HDF treatment were compared. In terms of safety, the study was meticulous in recording vital signs and the incidence of adverse events throughout its duration.
RESULTS
The study enrolled 20 patients. After a single HFR treatment, levels of IS, λFLC, β-MG, IL-6, P-cresol, YKL-40, LEP, HPA, TMAO, ADMA, TNF-α, and FGF23 significantly decreased ( < 0.001 for all). The clearance rates of λFLC, β-MG, IL-6, LEP, and TNF-α were significantly higher in HFR compared to HDF ( values: 0.036, 0.042, 0.041, 0.019, and 0.036, respectively). Compared with pre-HFR and post-HFR treatment, levels of serum albumin, valine, and isoleucine showed no significant difference ( > 0.05), while post-HDF, levels of serum albumin significantly decreased ( = 0.000).
CONCLUSION
HFR treatment effectively eliminates uremic toxins from the bloodstream of patients undergoing MHD, especially protein-bound toxins and large middle-molecule toxins. Additionally, it retains essential physiological compounds like albumin and branched-chain amino acids, underscoring its commendable safety profile.
Topics: Humans; Hemodiafiltration; Pilot Projects; Uremic Toxins; Chitinase-3-Like Protein 1; Interleukin-6; Tumor Necrosis Factor-alpha; Renal Dialysis; Amino Acids, Branched-Chain; Serum Albumin; Cresols; Methylamines
PubMed: 38632963
DOI: 10.1080/0886022X.2024.2338929