Beta 2-microglobulin Levels Research Articles

Isatuximab-dexamethasone-pomalidomide combination effects on serum M protein and PFS in myeloma: Development of a joint model using phase I/II data.

This study aimed at leveraging data from phase I/II clinical trials to build a nonlinear joint model of serum M-protein kinetics and progression-free survival (PFS) accounting for the effects of isatuximab (Isa), pomalidomide (Pom), and dexamethasone (Dex) in patients with relapsed and/or refractory multiple myeloma. Serum M-protein levels and PFS data from 203 evaluable patients, included either in a phase I/II study (n = 173) or in a phase I study (n = 30), were used to build the model. First, we independently developed a longitudinal model and a PFS model. Then, we linked them in a nonlinear joint model by selecting the link function that best captured the association between serum M-protein kinetics and PFS. A Claret tumor growth-inhibition model accounting for the additive effects of Isa, with an Emax function, Pom, and Dex on serum M-protein elimination was selected to describe serum M-protein kinetics. PFS was best described with a log-logistic model and associations with baseline beta-2 microglobulin level, age, and coadministration of Dex were identified. The instantaneous change in serum M-protein level was found to be associated with PFS in the final joint model. Using model simulations, we retrospectively supported the Isa 10 mg/kg weekly for 4 weeks, then biweekly (QW/Q2W) dosing regimen of the ICARIA-MM phase III pivotal study, and validated it using the same phase III pivotal study data.

Low Serum Beta-2 Microglobulin Level: A Possible Biomarker for Sarcopenia in the Elderly Population.

Background and Objectives: One of the most critical problems regarding sarcopenia is the difficulty of the diagnosis process. This study aimed to determine the prevalence and investigate the role of serum beta-2 microglobulin level as a biomarker for diagnosing sarcopenia. Materials and Methods: This nested case-control study was conducted between 2023 and 2024 on 251 older adults. Muscle strength was measured using a hand dynamometer, and muscle mass was assessed using the bioelectrical impedance method. Individuals with low muscle strength and low muscle mass were accepted as having definitive sarcopenia. Results: The mean age of the 251 older adults included in the study was 72.19 ± 6.11 years. The prevalence of sarcopenia in individuals aged 65 years and over was found to be 5.2%. Serum beta-2 microglobulin levels were statistically significantly lower in sarcopenic participants compared to the control group (p = 0.002). The optimal cut-off value for serum beta-2 microglobulin level was 2.26 mcg/mL, and values lower than this point were found to be diagnostic for sarcopenia. Regarding the cut-off value, the sensitivity was 92.31% and the specificity was 80.77%, the positive predictive value was 70.59%, the negative predictive value was 95.45%, the Youden index was 0.731, and the area under the curve value was 0.901. Individuals who had beta-2 microglobulin levels below 2.26 mcg/mL were found to have a 10.75 times higher risk of sarcopenia. Conclusions: A low serum beta-2 microglobulin level has the potential to be an important candidate biomarker for the diagnosis of sarcopenia.

Meta-analyses of epigenetic age acceleration and GrimAge components of schizophrenia or first-episode psychosis

Schizophrenia is a common chronic psychiatric disorder that causes age-related dysfunction. The life expectancy in patients with schizophrenia is ≥10 years shorter than that in the general population because of the higher risk of other diseases, such as cardiovascular diseases. Aging studies based on DNA methylation status have received considerable attention. Several epigenetic age accelerations and predicted values of aging-related proteins (GrimAge and GrimAge2 components) have been analyzed in multiple diseases. However, no studies have investigated up to GrimAge and GrimAge2 components between patients with schizophrenia and controls. Therefore, we aimed to conduct multiple regression analyses to investigate the association between schizophrenia and epigenetic age accelerations and GrimAge and GrimAge2 components in seven cohorts. Furthermore, we included patients with first-episode psychosis whose illness duration was often shorter than schizophrenia in our analysis. We integrated these results with meta-analyses, noting the acceleration of GrimAge, GrimAge2, and DunedinPACE, and increase in adrenomedullin, beta-2 microglobulin, cystatin C, and plasminogen activation inhibitor-1 levels, in patients with schizophrenia or first-episode psychosis. These results corroborated the finding that patients with schizophrenia had an increased risk of diabetes, cardiovascular disease, and cognitive dysfunction from a biological perspective. Patients with schizophrenia and first-episode psychosis showed differences in the results when compared with controls. Such analyses may lead to the development of novel therapeutic targets to patients with schizophrenia or relevant diseases from the perspective of aging in the future.

Beta-2-Microglobulin Maintains Overall Survival Prediction in Binet A Stage Chronic Lymphocytic Leukemia Patients with Compromised Kidney Function in Both Treatment Eras of Chemoimmunotherapy and Targeted Agents.

Background: Elevated beta-2-microglobulin (B2M) plasma levels commonly imply a higher CLL-IPI risk category for short overall survival (OS), but the risk model was not adjusted for compromised kidney function and not validated in Binet A stage CLL patients. Methods: CLL patients were identified from 2000 to 2022 at Innsbruck University Hospital, Austria. B2M levels, CLL-IPI risk stratification, and kidney function were assessed. Treatment modalities in case of disease progression and OS data during follow-up were evaluated. Results: A total of 259 Binet A stage CLL patients were identified; 16.9% (n = 44/259) presented with concurrent chronic kidney disease (CKD, GFR < 60 mL/min). Median OS was 170 months and was similar in CKD and non-CKD patients (p = 0.25). The CLL-IPI facilitated prognostic segregation in both CKD (p = 0.02) and non-CKD patients (p = 0.008). Although more frequently elevated in CKD patients (44.1% versus 10.6%, p < 0.001), B2M > 3.5 mg/L remained associated with inferior OS in this subgroup (p = 0.03). Contrary to the CLL-IPI, the prognostic value of B2M alone was also maintained in CLL patients diagnosed and potentially treated frontline in the era of targeted agents (2014-2022, p = 0.03). Conclusions: B2M retains its prognostic value for OS in early-stage CLL patients with concurrent CKD and still represents a promising covariate for up-coming prognostic models to identify patients at high risk for inferior OS in the era of targeted agents.

Survival Outcomes of Patients with Primary Plasma Cell Leukemia in the Era of Proteasome Inhibitors and Immunomodulatory Agents: A Real-Life Multicenter Analysis.

In this study, we aimed to obtain real-life data on the use of antimyeloma agents, which significantly increase overall survival (OS) in multiple myeloma (MM) patients, in primary plasma cell leukemia (pPCL) patients with a poor prognosis. Data from 53 patients who were diagnosed with pPCL between 2011-2020 and who used at least one proteasome inhibitor (PI) and/or immunomodulatory (IMID) agent were analyzed retrospectively. Depending on the year of pPCL diagnosis, 20% leukocytes or ≥2×109/L plasma cells in the peripheral blood were used. The median age of the patients was 58 years, and 23 (43.4%) patients were over 65 years of age. For first-line treatment, PI or IMID alone was used in 31 (58.5%) patients, and PI and IMID were used simultaneously in 15 (28.3%) patients. Additionally, 21 (39.6%) patients received transplantation, and 13 (24.5%) patients received maintenance treatment. The median progression-free survival was 4 (1-42) months. When patients whose primary disease was refractory to first-line therapy were excluded, the duration of treatment was 6.5 months. The median OS was 15 months, with a median follow-up of 15 months. Only 7 (13.2%) of the patients were alive at the last follow-up visit. Those with higher beta-2 microglobulin levels and ISS stage 3 and nontransplant patients receiving first-line treatment had shorter OS (p=0.005, p=0.02 and p=0.008, respectively). Otherwise, the concomitant use of PIs and IMIDs, the addition of chemotherapy to induction therapy, and the response to induction therapy or maintenance therapy did not affect OS. In our study, as in previous similar studies, we could not see the increased survival trend in pPCL which is observed in MM. New studies are needed for pPCL patients, which is likely to increase with the new diagnostic criteria, based on current agents and information in MM.

Association of uremic toxins and systemic inflammation with depression and anxiety among hemodialysis patients in Montenegro.

The purpose of this study was to examine the association between uremic toxins, inflammation, depression and anxiety among hemodialysis patients in Montenegro. The cross-sectional study included 88 patients undergoing hemodialysis. Depression and anxiety symptoms were assessed by Patient Health Questionnaire (PHQ-9) and Beck Anxiety Inventory (BAI). The standard laboratory methods were used to measure uremic toxins and systemic inflammation (C-reactive protein, Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR)). Clinically significant depression (PHQ-9 ≥ 10) and anxiety (BAI ≥16) were found in 55.7% and 27.2%, respectively. Logistic regression analyses revealed that serum urea, beta 2-microglobulin (B2M), and systemic inflammation (CRP, NLR, PLR) were significantly and independently associated with depressive symptoms, whereas serum urea, creatinine, uric acid, B2M, and systemic inflammation (CRP nad NLR) were associated with anxiety symptoms. Depressive symptoms and anxiety are common among hemodialysis patients in Montenegro, and are associated with increased levels of systematic inflammation, serum urea, and beta 2-microglobulin.

Evaluation of renal tubulointerstitial damage as a residual renal risk factor for adverse cardiac events in patients with aortic valve stenosis

Abstract Background Renal dysfunction, defined as a lower eGFR, has been shown to be related to cardiovascular events in patients with aortic stenosis treated with transcatheter aortic valve implantation (TAVI). However, the contribution of renal tubulointerstitial damage to the predictive value for cardiovascular events remains unclear. The aim of this study was to elucidate whether renal tubulointerstitial damage is associated with the occurrence of all death and heart failure patients who have had TAVI. Methods and results In a cohort of 155 patients, urinary beta2-microglobulin (beta2MG) levels were measured. Patients were monitored for less than three years or until experiencing all-cause mortality or hospitalization due to heart failure. The cumulative all-cause mortality was 11.5%, and heart failure admission rate stood at 5.4%. Stratifying outcomes by beta2MG levels revealed significantly lower rates of all-cause mortality and heart failure in patients with beta2MG &amp;lt;0.20 mg/gCre compared to those with beta2MG ≥0.20 mg/gCre (10.2% versus 24.2%, p=0.01). When outcomes were stratified according to the beta2MG levels in combination with eGFR levels, Kaplan-Meier analyses showed that all-cause mortality and heart failure rates increased depending on an increase in the beta2MG levels (p&amp;lt;0.05) even if eGFR is above 60 ml/min. Moreover, multivariate Cox analyses revealed that high levels of beta2MG were an independent predictor of adverse events. Conclusion Renal tubulointerstitial damage is associated with the occurrence of all death and hospitalization for heart failure independent of renal glomerular function.

The Vitamin C Level in Cases with Hematological Malignancies

Background: Oxidative stress plays a significant role in the pathogenesis of hematological malignan-cies. Vitamin C, known for its antioxidant properties, has garnered attention in this context. There-fore, we investigated vitamin C levels in patients with hematological malignancies and evaluated the relationship between vitamin C levels and response to treatment. Materials and Methods: Our study examined 150 cases of hematological malignancies and 30 he-althy cases. The vitamin C levels of patients with hematological malignancies were compared with those of the healthy group. Results: Vitamin C levels in cases of acute myeloblastic leukemia (n=30) (p&amp;lt;0.001), acute lympho-blastic leukemia (n=30) (p&amp;lt;0.001), Hodgkin lymphoma (n=30) (p&amp;lt;0.001), diffuse large B-cell lympho-ma (n=30) (p&amp;lt;0.001), and multiple myeloma (n=30) (p&amp;lt;0.001) were significantly lower compared to healthy individuals. There was a significant relationship between vitamin C levels and the response to treatment in cases with acute myeloblastic leukemia, acute lymphoblastic leukemia, Hodgkin lymphoma, diffuse large B-cell lymphoma, and multiple myeloma (p=0.020, p=0.020, p=0.040, p&amp;lt;0.001, p&amp;lt;0.001, respectively). In Hodgkin and non-Hodgkin lymphoma cases, a negative correla-tion was found between vitamin C levels and LDH and beta-2 microglobulin levels (p=0.001; p=0.008; p=0.017; p=0.019, respectively). Conclusions: Our study underscores the lower levels of vitamin C in patients with hematological malignancies compared to healthy individuals. Furthermore, the findings suggest that vitamin C levels could serve as a potential biomarker for predicting the response to treatment in these cases.

Unusual course of glyphosate-induced acute kidney injury: a case report of tubulointerstitial nephritis treated with steroids.

Glyphosate is a widely used herbicide that is generally considered safe; however, acute kidney injury (AKI) caused by glyphosate ingestion can be severe and require hemodialysis. We present a unique case of a 68-year-old Japanese man who developed AKI after accidental ingestion of glyphosate and required hemodialysis. Based on the clinical presentation and findings, the patient was diagnosed with renal AKI with severe tubulointerstitial damage. However, the precise pathogenesis of the tubulointerstitial damage remained unclear. An elevated beta-2 microglobulin level discovered by the urinalysis during admission raised the suspicion of tubulointerstitial nephritis caused by glyphosate. Gallium scintigraphy revealed accumulation in both kidneys. A renal biopsy revealed acute tubulointerstitial nephritis rather than acute tubular necrosis, which is commonly observed with glyphosate-induced renal injury. After initiating steroid therapy, his kidney function gradually improved and he was weaned from hemodialysis. This report is the first to describe glyphosate-induced acute tubulointerstitial nephritis that was successfully treated with immunosuppressive therapy. Furthermore, this report highlights the importance of steroid therapy for cases of persistent kidney injury after the discontinuation of agents associated with acute tubulointerstitial nephritis.

Dal rene all'occhio: che cos'è la TINU?

An eight-year-old boy presenting with interstitial nephritis (abdominal pain, microhematuria, glycosuria, proteinuria, elevated urinary beta2-microglobulin levels) was eventually diagnosed with TINU syndrome (tubulointerstitial nephritis associated with uveitis) following the late onset of uveitis.

A safe and effective protocol for postdilution hemofiltration with regional citrate anticoagulation

BackgroundRegional citrate anticoagulation (RCA) is recommended during continuous renal replacement therapy. Compared to systemic anticoagulation, RCA provides a longer filter lifespan with the risk of metabolic alkalosis and impaired calcium homeostasis. Surprisingly, most RCA protocols are designed for continuous veno-venous hemodialysis or hemodiafiltration. Effective protocols for continuous veno-venous hemofiltration (CVVH) are rare, although CVVH is a standard treatment for high-molecular-weight clearance. Therefore, we evaluated a new RCA protocol for postdilution CVVH.MethodsThis is a monocentric prospective interventional study to evaluate a new RCA protocol for postdilution CVVH. We recruited surgical patients with stage III acute kidney injury who needed renal replacement therapy. We recorded dialysis and RCA data and hemodynamic and laboratory parameters during treatment sessions of 72 h. The primary endpoint was filter patency at 72 h. The major safety parameters were metabolic alkalosis and severe hypocalcemia at any time.ResultsWe included 38 patients who underwent 66 treatment sessions. The mean filter lifespan was 66 ± 12 h, and 44 of 66 (66%) filters were patent at 72 h. After censoring for non-CVVH-related cessation of treatment, 83% of all filters were patent at 72 h. The delivered dialysis dose was 28 ± 5 ml/kgBW/h. The serum levels of creatinine, urea and beta2-microglobulin decreased significantly from day 0 to day 3. Metabolic alkalosis occurred in one patient. An iCa++ below 1.0 mmol/L occurred in four patients. Citrate accumulation did not occur.ConclusionsWe describe a safe, effective, and easy-to-use RCA protocol for postdilution CVVH. This protocol provides a long and sustained filter lifespan without serious adverse effects. The risk of metabolic alkalosis and hypocalcemia is low. Using this protocol, a recommended dialysis dose can be safely administered with effective clearance of low- and middle-molecular-weight molecules.Trial registrationThe study was approved by the medical ethics committee of Heinrich-Heine University Duesseldorf (No. 2018-82KFogU). The trial was registered in the local study register of the university (No: 2018044660) on 07/04/2018 and was retrospectively registered at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT03969966) on 31/05/2019.

Assessment of Serum Beta 2-Microglobulin Levels in Crimean-Congo Hemorrhagic Fever Patients: Implications for Immune Activation and Disease Pathogenesis

Crimean-Congo Hemorrhagic Fever (CCHF) presents a spectrum of clinical manifestations, ranging from asymptomatic cases to severe, life-threatening conditions. Despite extensive research on CCHF pathogenesis, comprehensive understanding remains elusive. Our investigation focused on assessing serum beta 2-microglobulin (β2M) levels in CCHF patients, aiming to elucidate its potential as an immune activation marker and its involvement in disease pathogenesis. The study enrolled 45 CCHF patients and 45 healthy volunteers as a control group. Serum β2M levels were quantified using the immunoturbidimetric analysis method. The patient group was divided into two groups, mild and moderate-severe, using scoring systems. The mean β2M values for the control, mild, and moderate-severe patient groups were 2.27±0.50, 4.37±1.29, and 5.82±2.62 mg/L, respectively (p&amp;lt;0.001). Positive correlations were noted between β2M concentrations and markers such as BUN, creatinine, uric acid, creatine kinase, and aPTT (p&amp;lt;0.001, r=0.684; p&amp;lt;0.001, r=0.602; p=0.003, r=0.439; p=0.008, r=0.392; p=0.019, r=0.348, respectively). Conversely, negative correlations were observed with total protein, albumin, and platelet count (p=0.021, r=-0.342; p=0.003, r=-0.434; p=0.048, r=-0.296, respectively). The findings suggest a prominent inflammatory response in CCHF, indicated by elevated β2M levels, implying its potential role in the molecular mechanisms of the disease

Value of Serum Beta2-Microglobulin Level in Prediction of Acute kidney injury in Critically Ill Neonates.

Value of Serum Beta2-Microglobulin Level in Prediction of Acute kidney injury in Critically Ill Neonates.

Serum beta2-microglobulin acts as a biomarker for severity and prognosis in glioma patients: a preliminary clinical study

BackgroundGliomas are the deadliest malignant tumors of the adult central nervous system. We previously discovered that beta2-microglobulin (B2M) is abnormally upregulated in glioma tissues and that it exerts a range of oncogenic effects. Besides its tissue presence, serum B2M levels serve as biomarkers for various diseases. This study aimed to explore whether serum B2M levels can be used in the diagnosis and prognosis of gliomas.MethodsMedical records from 246 glioma patients were retrospectively analyzed. The relationship between preoperative serum B2M levels and clinicopathological features was examined. Kaplan-Meier analysis, alongside uni- and multivariate Cox regression, assessed the association between B2M levels, systemic inflammatory markers, and glioma patient prognosis. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic significance of these biomarkers specifically for glioblastoma (GBM).ResultsPatients with malignant gliomas exhibited elevated preoperative serum B2M levels. Glioma patients with high serum B2M levels experienced shorter survival times. Multivariate Cox analysis determined the relationship between B2M levels (hazard ratio = 1.92, 95% confidence interval: 1.05–3.50, P = 0.034) and the overall survival of glioma patients. B2M demonstrated superior discriminatory power in distinguishing between GBM and non-GBM compared to inflammation indicators. Moreover, postoperative serum B2M levels were lower than preoperative levels in the majority of glioma patients.ConclusionsHigh preoperative serum B2M levels correlated with malignant glioma and a poor prognosis. Serum B2M shows promise as a novel biomarker for predicting patient prognosis and reflecting the therapeutic response.

Urinary beta-2 microglobulin increases whereas TIMP-2 and IGFBP7 decline after unilateral nephrectomy in healthy kidney donors

Early kidney injury may be detected by urinary markers, such as beta-2 microglobulin (B2M), tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), kidney injury molecule-1 (KIM-1) and/or neutrophil gelatinase-associated lipocalin (NGAL). Of these biomarkers information on pathophysiology and reference ranges in both healthy and diseased populations are scarce. Differences in urinary levels of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL were compared 24 h before and after nephrectomy in 38 living kidney donors from the REnal Protection Against Ischaemia–Reperfusion in transplantation study. Linear regression was used to assess the relation between baseline biomarker concentration and kidney function 1 year after nephrectomy. Median levels of urinary creatinine and creatinine standardized B2M, TIMP-2, IGFBP7, KIM-1, NGAL, and albumin 24 h before nephrectomy in donors were 9.4 mmol/L, 14 μg/mmol, 16 pmol/mmol, 99 pmol/mmol, 63 ng/mmol, 1390 ng/mmol and 0.7 mg/mmol, with median differences 24 h after nephrectomy of − 0.9, + 1906, − 7.1, − 38.3, − 6.9, + 2378 and + 1.2, respectively. The change of donor eGFR after 12 months per SD increment at baseline of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL was: − 1.1, − 2.3, − 0.7, − 1.6 and − 2.8, respectively. Urinary TIMP-2 and IGFBP7 excretion halved after nephrectomy, similar to urinary creatinine, suggesting these markers predominantly reflect glomerular filtration. B2M and NGAL excretion increased significantly, similar to albumin, indicating decreased proximal tubular reabsorption following nephrectomy. KIM-1 did not change considerably after nephrectomy. Even though none of these biomarkers showed a strong relation with long-term donor eGFR, these results provide valuable insight into the pathophysiology of these urinary biomarkers.

#1372 Association of plasma beta-2-microglobulin with risk of cardiovascular disease in patients with chronic kidney disease

Abstract Background and Aims In patients with chronic kidney disease(CKD), beta 2 microglobulin (B2MG) can be used to assess renal function, and predialysis serum B2MG levels can predict mortality risk. In addition to the kidney, B2MG regulates the expression of interleukin 1 and tumor necrosis factor, participates in the pathogenesis of vascular damage, and is a marker that can detect the formation of amyloid, therefore it is important in the diagnosis of cardiovascular disease (CVD). To assess the correlation of serum B2MG levels with some metabolic and cardiovascular function factors in patients with chronic kidney disease. Method 119 people with chronic kidney disease and 52 healthy control groups were selected as a case-control study and blood samples were analyzed for creatinine, urea, cholesterol, triglycerides, LDL, calcium, phosphorus, albumin, total protein, and B2MG with Cobas 6000 fully automatic analyzer and echocardiography was performed. Renal function was evaluated by CKD EPI crea-cys combined calculation. In the group with CKD, a person with eGFR &amp;lt;90 ml/min/1.73 m² was not included in the study due to the study exclusion criteria. Results The average age of the group with CKD was 54.92, and the average age of the healthy group was 50.66. B2MG has a significantly higher (P &amp;lt; 0.000) statistically significant correlation in the group with CKD compared to the control group. B2MG was significantly associated with creatinine (g = 0.516, P &amp;lt; 0.000), phosphorus (g = 0.342, P &amp;lt; 0.000), cystatin C (g = 0.700, P &amp;lt; 0.000), urea (g = 0.326, P &amp;lt; 0.000), and echocardiography with directly indicators LVMI(g = 0.113, P &amp;lt; 0.000), LVESD (r = 0.265, P &amp;lt; 0.000), thus BMI (g = −0.274, P &amp;lt; 0.000), tTSH (r = −0.516, P &amp;lt; 0.000), calcium ( g = −0.137, P &amp;lt; 0.000), albumin (g = −0.180, P &amp;lt; 0.000), total protein (r = −0.080, P &amp;lt; 0.000), cholesterol (g = −0.215, P &amp;lt; 0.000), BNLP (r = −0.163, P &amp;lt; 0.000), triglycerides (g = −0.142, P &amp;lt; 0.000), and EV of echocardiography (g = −0.292, P &amp;lt; 0.000) have inverse statistical significance. Conclusion B2MG levels have been shown to predict CVD risk and CVD-related mortality in all stages of chronic kidney disease. According to our study, B2MG is directly related to kidney function biomarkers, phosphorus, LVMI, and LVESD indicators of cardiac echocardiography, and inversely correlated with parameters of eGFR, protein, triglycerides, calcium, and cardiac echocardiogram EV indicators, which is similar to studies conducted in other countries. Therefore, B2MG can be used to detect the risk of CVD in people with severe CKD. Figure: Will be uploaded on our poster if accepted.

Association of serum protein electrophoresis with clinicopathological characteristics and its prognostic relevance in chronic lymphocytic leukaemia patients.

To assess the association of serum protein electrophoresis abnormalities with clinicopathological characteristics, and its impact on overall survival in chronic lymphocytic leukaemia patients. 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. 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). Abnormal serum protein electrophoresis could be considered a surrogate marker for advanced chronic lymphocytic leukaemia disease.

Primary thyroid lymphoma: a case series

IntroductionPrimary Thyroid Lymphoma (PTL) is defined as lymphoma involving the thyroid gland alone or the thyroid gland and adjacent neck lymph nodes without contiguous spread or distant metastases at the time of diagnosis. Most thyroid lymphomas are B cell lymphomas, and 98% of all PTL cases are non-Hodgkin’s lymphoma. It is a rare disease accounting for around 5% of the thyroid neoplasms and 2% of extranodal lymphomas. If properly diagnosed and treated, the prognosis is favorable.Case presentationFive cases (three men and two women) of PTL were diagnosed and treated in our institute between January 2005 and September 2019. These are 5 cases of Caucasian origin. The mean age was 76.2 (range: 63–95 years); one patient had associated hypothyroid. One patient had a medical history of breast cancer; one was hypothyroid, and four were euthyroid at the diagnosis. In 4 of these patients, PTL started with compressive symptoms. No patients underwent fine needle aspiration cytology (FNAC) or biopsy for the diagnostic only. In sonography, two cases showed bilateral nodules with goiter; in the three cases it showed nodules in the lobe and isthmus. Technetium-99m scintigraphy was performed on only two patients. Bone Marrow Biopsy (BMB) showed normal cellularity in 4 cases and only one case showed tumor cells. LDH levels were increased in all cases. The extension was evaluated in all patients with cervical and thoracic CT scans, Bone Marrow Biopsy (BMB), beta-2 microglobulin, and serum lactate dehydrogenase (LDH) levels. Three cases were staged as IE and two cases as IIE. Three patients underwent total thyroidectomy; two of them underwent cervical lymph node dissection. Two patients underwent lobectomy. All were diagnosed with lymphoma postoperatively and all were diffuse large B cell lymphoma (DLBCL). One patient completed treatment with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone), and two cases received adjuvant chemo-radiotherapy (30 Gy). Two patients died immediately after surgery.ConclusionPTL is a rare disease whose diagnosis should be considered in cases of rapidly growing goitres. Timely needle biopsy in suspected cases can avoid unnecessary surgery. Systemic treatment is required, depending on the stage of the tumour.

B Cell Subsets and Immune Checkpoint Expression in Patients with Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is characterized by dysfunctional B cells. Immune checkpoint molecules such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death-1 (PD-1) are upregulated in patients with CLL and may correlate with prognostic markers such as beta-2 microglobulin (B2M). The aim of this study was to evaluate the levels of immune checkpoints on B cell subsets and to further correlate them with B2M levels in patients with CLL. We recruited 21 patients with CLL and 12 controls. B cell subsets and the levels of immune checkpoint expression were determined using conventional multi-color flow cytometry. Basal levels of B2M in patients with CLL were measured using an enzyme-linked immunosorbent assay. Patients with CLL had increased levels of activated B cells when compared to the control group, p < 0.001. The expression of PD-1 and CTLA-4 were increased on activated B cells and memory B cells, p < 0.05. There were no associations between B2M levels and the measured immune checkpoints on B cell subsets, after adjusting for sex and age. In our cohort, the patients with CLL expressed elevated levels of PD-1 and CTLA-4 immune checkpoints on activated and memory B cell subsets. However, there was no correlation between these immune checkpoint expressions and B2M levels.

Tumor beta2-microglobulin and HLA-A expression is increased by immunotherapy and can predict response to CIT in association with other biomarkers.

Downregulation of MHC class I expression and/or defects in the antigen presentation pathways are commonly reported in human cancers. Numerous studies previously have explored extensively the molecular mechanisms that underlie HLA-class I and Beta2-Microglobulin (B2M) downregulation. However, the techniques presently available to detect expression of MHC class I proteins lack the robustness, specificity and sensitivity needed for systematic integration and analysis in clinical trials. Furthermore, the dynamics of HLA-class I and B2M expression have not been comprehensively studied as a potential biomarker for immunotherapy. Using novel, validated, immunohistochemistry (IHC)-based methods for quantifying B2M and HLA-A in tumor samples from diverse cancer types, we have determined loss of B2M and HLA-A proteins in 336 archived, primary specimens and 329 biopsies from metastatic patients collected during Roche-sponsored Phase 1 clinical trials investigating novel immunotherapy candidates as monotherapy or in combination with CPI. Up to 56% of cases with B2M or HLA-A loss were noted in the investigated tumor types. The frequency of loss was dependent on indication and stage of disease and revealed heterogeneous expression patterns across patients. B2M and HLA-A loss was increased in metastatic lesions compared to primary tumors, indicating selection of MHC class I low clones in metastatic and refractory tumor cells. High on-treatment B2M expression correlated with successful clinical outcome (RECIST), while high baseline B2M did not. A treatment-induced increase of B2M expression was noted in most of the patients with low B2M levels at baseline. The triple biomarker combination of B2M, CD8 and PDL1 strongly improved response prediction to cancer immunotherapy. Our results indicate that B2M and HLA-A loss occurs frequently in tumors and is reversed in most instances following immunotherapy which supports the conclusion that MHC class I loss is not the dominant resistance mechanism to CPI treatment. This investigation reveals a highly dynamic expression of HLA-A and B2M in tumors affected by indication, metastatic status, immunophenotype and immunotherapy treatment. Baseline expression levels of B2M on tumors may be of utility as a constituent of a biomarker panel used for selecting patients for immunotherapy clinical trials.