Did you mean: beta microglobulin
-
American Journal of Hematology Feb 2023Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia,...
DISEASE OVERVIEW
Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity.
DIAGNOSIS
Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in most IgM MGUS patients. MYD88 is not required for the diagnosis.
RISK STRATIFICATION
Age, hemoglobin level, platelet count, β microglobulin, LDH, and monoclonal IgM concentrations are characteristics that are predictive of outcomes.
RISK-ADAPTED THERAPY
Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-monotherapy is inferior to regimens that combine it with bendamustine, an alkylating agent, a proteosome inhibitor, or a BTK inhibitor. The preferred Mayo Clinic induction is either rituximab and bendamustine (without rituximab maintenance) or zanubrutinib.
MANAGEMENT OF REFRACTORY DISEASE
Bortezomib, cyclophosphamide, fludarabine, thalidomide, everolimus, Bruton Tyrosine Kinase inhibitors, carfilzomib, lenalidomide, bendamustine, and venetoclax have all been shown to have activity in relapsed WM. Given WM's natural history, the reduction of therapy toxicity is an important part of treatment selection.
Topics: Humans; Waldenstrom Macroglobulinemia; Rituximab; Bendamustine Hydrochloride; Myeloid Differentiation Factor 88; Antibodies, Monoclonal; Paraproteins; Risk Assessment; Immunoglobulin M
PubMed: 36588395
DOI: 10.1002/ajh.26796 -
American Journal of Hematology Feb 2021Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia,... (Review)
Review
DISEASE OVERVIEW
Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity.
DIAGNOSIS
Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in the majority of IgM MGUS patients.
RISK STRATIFICATION
Age, hemoglobin level, platelet count, β microglobulin, LDH and monoclonal IgM concentrations are characteristics that are predictive of outcomes.
RISK-ADAPTED THERAPY
Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-monotherapy is inferior to regimens that combine it with bendamustine, an alkylating agent, a proteosome inhibitor, or ibrutinib. Purine nucleoside analogues are active but usage is declining in favor of less toxic alternatives. The preferred Mayo Clinic induction is rituximab and bendamustine.
MANAGEMENT OF REFRACTORY DISEASE
Bortezomib, fludarabine, thalidomide, everolimus, Bruton Tyrosine Kinase inhibitors, carfilzomib, lenalidomide, and bendamustine have all been shown to have activity in relapsed WM. Given WM's natural history, reduction of therapy toxicity is an important part of treatment selection.
Topics: Age Factors; Humans; Immunoglobulin M; L-Lactate Dehydrogenase; Mutation, Missense; Myeloid Differentiation Factor 88; Platelet Count; Risk Assessment; Waldenstrom Macroglobulinemia
PubMed: 33368476
DOI: 10.1002/ajh.26082 -
International Journal of... 2022Pott's disease is a vertebral infection caused by Mycobacterium tuberculosis. Indolent nature and subacute course are associated with late diagnosis. A clinical case is...
Pott's disease is a vertebral infection caused by Mycobacterium tuberculosis. Indolent nature and subacute course are associated with late diagnosis. A clinical case is presented whose diagnosis was delayed by atypical presentation with progressive worsening of symptoms. Magnetic resonance imaging (MRI) of the dorsolumbar spine revealed T7-T8 angulation suggestive of secondary injury, with intracanalar extension and spinal cord compression. Gastric aspirate cultures, direct microscopy, and polymerase chain reaction (PCR) were A 79-yearold female came to the emergency department with right back pain, pleuritic, with 12 h of evolution. Anorexia and weight loss,1 month evolution. Computed tomography (CT) of the dorsal spine revealed T7-T8 lytic lesions, suggestive of secondary nature. Objectively:weight loss and pain during thoracic palpation. Annalistically: normocytic/normochromic anemia, hypercalcemia, hepatic cholestasis, C-reactive protein (CRP) 7.12 mg/dL. Chest X-ray and electrocardiogram without alterations. She was admitted in Internal Medicine service. Analytically: hypophosphatemia, parathyroid hormone elevated, CRP 6 mg/dL, Beta-2 microglobulin elevated, dyslipidemia, iron and folicacid deficiency.negative for M. tuberculosis. T8 aspiration CT guided: cultures/direct microscopy negative, PCR positive for M. tuberculosis. Introductionof antitubercular drugs. Worsening of symptomatology, with paraparesia. MRI of the dorsal spine revealed spondylodiscitis and spinal cordcompression in T7-T8. Diagnosis revealed vertebral tuberculosis with spinal cord compression. She was transferred to neurosurgery servicefor surgical treatment. There was clinical and analytical improvement. Draws attention to difficulty in diagnose a treatable disease in a patientwith a rare presentation.
Topics: Aged; Antitubercular Agents; Female; Humans; Mycobacterium tuberculosis; Spinal Cord Compression; Tuberculosis, Spinal; Weight Loss
PubMed: 35295033
DOI: 10.4103/ijmy.ijmy_2_22 -
Immunity Aug 2021As substantial constituents of the multiple myeloma (MM) microenvironment, pro-inflammatory macrophages have emerged as key promoters of disease progression, bone...
As substantial constituents of the multiple myeloma (MM) microenvironment, pro-inflammatory macrophages have emerged as key promoters of disease progression, bone destruction, and immune impairment. We identify beta-2-microglobulin (β2m) as a driver in initiating inflammation in myeloma-associated macrophages (MAMs). Lysosomal accumulation of phagocytosed β2m promotes β2m amyloid aggregation in MAMs, resulting in lysosomal rupture and ultimately production of active interleukin-1β (IL-1β) and IL-18. This process depends on activation of the NLRP3 inflammasome after β2m accumulation, as macrophages from NLRP3-deficient mice lack efficient β2m-induced IL-1β production. Moreover, depletion or silencing of β2m in MM cells abrogates inflammasome activation in a murine MM model. Finally, we demonstrate that disruption of NLRP3 or IL-18 diminishes tumor growth and osteolytic bone destruction normally promoted by β2m-induced inflammasome signaling. Our results provide mechanistic evidence for β2m's role as an NLRP3 inflammasome activator during MM pathogenesis. Moreover, inhibition of NLRP3 represents a potential therapeutic approach in MM.
Topics: Amyloid; Animals; Cells, Cultured; Humans; Inflammation; Interleukin-18; Interleukin-1beta; Lysosomes; Mice; Mice, Inbred C57BL; Mice, Knockout; Multiple Myeloma; NLR Family, Pyrin Domain-Containing 3 Protein; Phagocytosis; Signal Transduction; Tumor Microenvironment; Tumor-Associated Macrophages; beta 2-Microglobulin
PubMed: 34289378
DOI: 10.1016/j.immuni.2021.07.002 -
Kidney360 Feb 2023Incremental peritoneal dialysis (IPD) is a strategy of RRT that is based on the prescription of a lower dose rather than the standard full dose of peritoneal dialysis... (Review)
Review
Incremental peritoneal dialysis (IPD) is a strategy of RRT that is based on the prescription of a lower dose rather than the standard full dose of peritoneal dialysis (PD). The clearance goals are achieved through the combination of residual kidney function (RKF) and peritoneal clearance. The dialysis prescription should be increased as the RKF declines. IPD has been associated with clinical, economic, and environmental advantages. We emphasize possible better quality of life, fewer mechanical symptoms, lower costs, slight adverse metabolic effects, and less plastic waste and water consumption. The potential benefits for RKF preservation and the lower risk of peritonitis have also been discussed. There are some concerns regarding this strategy, such as inadequate clearance of uremic toxins and/or severe electrolyte disturbances due to undetected loss of RKF, lower clearance of medium-sized molecules (such as β-2-microglobulin) which mostly depends on the total PD dwell time, and patients' reluctance to dose adjustments. Current clinical evidence is based on moderate-quality to low-quality studies and suggests that the outcomes of IPD will be at least identical to those of full dose. This review aims to define IDP, discuss strategies for prescription, and review its advantages and disadvantages according to the current evidence.
Topics: Humans; Peritoneal Dialysis; Peritoneum; Prescriptions; Quality of Life; Renal Dialysis
PubMed: 36821618
DOI: 10.34067/KID.0006902022 -
Nature Jan 2023DNA mismatch repair-deficient (MMR-d) cancers present an abundance of neoantigens that is thought to explain their exceptional responsiveness to immune checkpoint...
DNA mismatch repair-deficient (MMR-d) cancers present an abundance of neoantigens that is thought to explain their exceptional responsiveness to immune checkpoint blockade (ICB). Here, in contrast to other cancer types, we observed that 20 out of 21 (95%) MMR-d cancers with genomic inactivation of β2-microglobulin (encoded by B2M) retained responsiveness to ICB, suggesting the involvement of immune effector cells other than CD8 T cells in this context. We next identified a strong association between B2M inactivation and increased infiltration by γδ T cells in MMR-d cancers. These γδ T cells mainly comprised the Vδ1 and Vδ3 subsets, and expressed high levels of PD-1, other activation markers, including cytotoxic molecules, and a broad repertoire of killer-cell immunoglobulin-like receptors. In vitro, PD-1 γδ T cells that were isolated from MMR-d colon cancers exhibited enhanced reactivity to human leukocyte antigen (HLA)-class-I-negative MMR-d colon cancer cell lines and B2M-knockout patient-derived tumour organoids compared with antigen-presentation-proficient cells. By comparing paired tumour samples from patients with MMR-d colon cancer that were obtained before and after dual PD-1 and CTLA-4 blockade, we found that immune checkpoint blockade substantially increased the frequency of γδ T cells in B2M-deficient cancers. Taken together, these data indicate that γδ T cells contribute to the response to immune checkpoint blockade in patients with HLA-class-I-negative MMR-d colon cancers, and underline the potential of γδ T cells in cancer immunotherapy.
Topics: Humans; Colonic Neoplasms; Histocompatibility Antigens Class I; Immune Checkpoint Inhibitors; Immunotherapy; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocytes; beta 2-Microglobulin; DNA Mismatch Repair; Receptors, KIR; Cell Line, Tumor; Organoids; Antigen Presentation; Genes, MHC Class I
PubMed: 36631610
DOI: 10.1038/s41586-022-05593-1 -
Free Radical Biology & Medicine Jul 2022Beta-2-microglobulin (B2M) is synthesized by all nucleated cells and forms part of the major histocompatibility complex (MHC) class-1 present on cell surfaces, which...
Beta-2-microglobulin (B2M) is synthesized by all nucleated cells and forms part of the major histocompatibility complex (MHC) class-1 present on cell surfaces, which presents peptide fragments to cytotoxic CD8 T-lymphocytes, or by association with CD1, antigenic lipids to natural killer T-cells. Knockout of B2M results in loss of these functions and severe combined immunodeficiency. Plasma levels of this protein are low in healthy serum, but are elevated up to 50-fold in some pathologies including chronic kidney disease and multiple myeloma, where it has both diagnostic and prognostic value. High levels of the protein are associated with amyloid formation, with such deposits containing significant levels of modified or truncated protein. In the current study we examine the chemical and structural changes induced of B2M generated by both inflammatory oxidants (HOCl and ONOOH), and photo-oxidation (O) which is linked with immunosuppression. Oxidation results in oligomer formation, with this occurring most readily with HOCl and O, and a loss of native protein conformation. LC-MS analysis provided evidence for nitrated (from ONOOH), chlorinated (from HOCl) and oxidized residues (all oxidants) with damage detected at Tyr, Trp, and Met residues, together with cleavage of the disulfide (cystine) bond. An intermolecular di-tyrosine crosslink is also formed between Tyr10 and Tyr63. The pattern of these modifications is oxidant specific, with ONOOH inducing a greater range of modifications than HOCl. Comparison of the sites of modification with regions identified as amyloidogenic indicate significant co-localization, consistent with the hypothesis that oxidation may contribute, and predispose B2M, to amyloid formation.
Topics: Chromatography, Liquid; Hypochlorous Acid; Oxidants; Oxidation-Reduction; Protein Conformation; Tyrosine
PubMed: 35609861
DOI: 10.1016/j.freeradbiomed.2022.05.012 -
Kidney360 Dec 2020Almost half a century has elapsed since the first description of dialysis-related amyloidosis (DRA), a disorder caused by excessive accumulation of -2 microglobulin... (Review)
Review
Almost half a century has elapsed since the first description of dialysis-related amyloidosis (DRA), a disorder caused by excessive accumulation of -2 microglobulin (B2M). Within that period, substantial advances in RRT occurred. These improvements have led to a decrease in the incidence of DRA. In many countries, DRA is considered a "disappearing act" or complication. Although the prevalence of patients living with RRT increases, not all will have access to kidney transplantation. Consequently, the number of patients requiring interventions for treatment of DRA is postulated to increase. This postulate has been borne out in Japan, where the number of patients with ESKD requiring surgery for carpal tunnel continues to increase. Clinicians treating patients with ESKD have treatment options to improve B2M clearance; however, there is a need to identify ways to translate improved B2M clearance into improved quality of life for patients undergoing long-term dialysis.
Topics: Amyloidosis; Carpal Tunnel Syndrome; Humans; Kidney Transplantation; Quality of Life; Renal Dialysis
PubMed: 35372889
DOI: 10.34067/KID.0004922020 -
Frontiers in Oncology 2022Despite the remarkable success of immunotherapy in the treatment of melanoma, resistance to these agents still affects patient prognosis and response to therapies.... (Review)
Review
Despite the remarkable success of immunotherapy in the treatment of melanoma, resistance to these agents still affects patient prognosis and response to therapies. Beta-2-microglobulin (β2M), an important subunit of major histocompatibility complex (MHC) class I, has important biological functions and roles in tumor immunity. In recent years, increasing studies have shown that B2M gene deficiency can inhibit MHC class I antigen presentation and lead to cancer immune evasion by affecting β2M expression. Based on this, B2M gene defect and T cell-based immunotherapy can interact to affect the efficacy of melanoma treatment. Taking into account the many recent advances in B2M-related melanoma immunity, here we discuss the immune function of the B2M gene in tumors, its common genetic alteration in melanoma, and its impact on and related improvements in melanoma immunotherapy. Our comprehensive review of β2M biology and its role in tumor immunotherapy contributes to understanding the potential of B2M gene as a promising melanoma therapeutic target.
PubMed: 36046045
DOI: 10.3389/fonc.2022.944722