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American Journal of Kidney Diseases :... May 2020Heavy chain deposition disease (HCDD) is a rare consequence of monoclonal immunoglobulin deposition disease that has not been well characterized in non-white...
RATIONALE & OBJECTIVE
Heavy chain deposition disease (HCDD) is a rare consequence of monoclonal immunoglobulin deposition disease that has not been well characterized in non-white populations. To explore the clinicopathologic characteristics and outcomes of HCDD in Chinese individuals, we report on a case series assembled in a single center in China.
STUDY DESIGN
Case series.
SETTING & PARTICIPANTS
25 patients with biopsy-proven HCDD were studied retrospectively.
RESULTS
14 men and 11 women with an average age of 50.3 years were studied. The patients presented with hypertension (76%), edema (96%), anemia (84%), serum creatinine level > 1.2mg/dL (68%), nephrotic-range proteinuria (56%), and microscopic hematuria (80%). One (4%) patient had multiple myeloma diagnosed. Serum immunofixation electrophoresis showed that 10 of 21 (48%) patients were positive for monoclonal immunoglobulin. Hypocomplementemia of C3 was found in 68% of patients. Nodular mesangial sclerosis was identified in all patients by using light microscopy. Using immunofluorescence, all 25 patients had deposition of heavy chains of immunoglobulin G class (γ1, 13; γ2, 2; γ3, 6; γ4, 2; γ1 and γ4, 1; and γ2 and γ4, 1). During an average of 40.1 months of follow-up of 20 patients, 65% had improved kidney function, 10% had worsening kidney function, and 25% progressed to kidney failure. Mean values for kidney and patient survival were 37.8 and 40.1 months, respectively. Kidney survival was higher among patients who received chemotherapy.
LIMITATIONS
Retrospective study, single-center experience.
CONCLUSIONS
In this case series of HCDD in a single center in China, the heavy chain deposits seen in the kidney biopies of all individuals were of immunoglobulin G class. Chemotherapy improved kidney function, especially among individuals in an early stage of the disease.
Topics: Adult; Antibodies, Monoclonal; Arterioles; China; Complement C3; Edema; Female; Glomerular Mesangium; Heavy Chain Disease; Hematuria; Humans; Immunoglobulin G; Kidney Failure, Chronic; Kidney Glomerulus; Male; Middle Aged; Prognosis; Retrospective Studies; Sclerosis
PubMed: 31699519
DOI: 10.1053/j.ajkd.2019.08.013 -
Pharmaceuticals (Basel, Switzerland) Jun 2019Iron is at the forefront of a number of pivotal biological processes due to its ability to readily accept and donate electrons. However, this property may also catalyze... (Review)
Review
Iron is at the forefront of a number of pivotal biological processes due to its ability to readily accept and donate electrons. However, this property may also catalyze the generation of free radicals with ensuing cellular and tissue toxicity. Accordingly, throughout evolution numerous pathways and proteins have evolved to minimize the potential hazardous effects of iron cations and yet allow for readily available iron cations in a wide variety of fundamental metabolic processes. One of the extensively studied proteins in the context of systemic and cellular iron metabolisms is ferritin. While clinicians utilize serum ferritin to monitor body iron stores and inflammation, it is important to note that the vast majority of ferritin is located intracellularly. Intracellular ferritin is made of two different subunits (heavy and light chain) and plays an imperative role as a safe iron depot. In the past couple of decades our understanding of ferritin biology has remarkably improved. Additionally, a significant body of evidence has emerged describing the significance of the kidney in iron trafficking and homeostasis. Here, we briefly discuss some of the most important findings that relate to the role of iron and ferritin heavy chain in the context of kidney-related diseases and, in particular, vascular calcification, which is a frequent complication of chronic kidney disease.
PubMed: 31234273
DOI: 10.3390/ph12020096 -
FEMS Microbiology Reviews Sep 2022The eukaryotic protein CD98hc (also known as 4F2, FRP-1, or SLC3A2) is a membrane glycoprotein and one of the heavy chains of the family of heterodimeric amino acids... (Review)
Review
The eukaryotic protein CD98hc (also known as 4F2, FRP-1, or SLC3A2) is a membrane glycoprotein and one of the heavy chains of the family of heterodimeric amino acids transporters. It can associate with any of 6 different light chains to form distinct amino acid transporters. CD98hc is also involved in mediation of intracellular integrin signaling. Besides its physiological roles in the development of the placenta and the immune system, CD98hc is important during pathological processes such as tumorigenesis and host-pathogen interaction. Since its first identification as Fusion Regulatory Protein 1 regulating cell fusion in cells infected by the Newcastle disease virus, CD98hc has been reported to be mediating many viral, apicomplexan, and bacterial infectious processes. In this review we describe the role of CD98hc and its associated light chains in bacterial, apicomplexan, and viral pathogenesis. We also discuss the consequences of infection on the expression and localization of these proteins. The identification of the cellular processes in which CD98hc is involved during pathogenesis highlights the key role of this host protein in infectious diseases.
Topics: Animals; Fusion Regulatory Protein 1, Heavy Chain; Signal Transduction
PubMed: 35595511
DOI: 10.1093/femsre/fuac023 -
Blood Jul 2017
Topics: Heavy Chain Disease; Humans; Immunoglobulin mu-Chains; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Neoplasm Proteins; Plasma Cells; Vacuoles
PubMed: 28751360
DOI: 10.1182/blood-2017-04-781344 -
Scientific Reports Dec 2023The functionally pleiotropic ectoenzyme CD38 is a glycohydrolase widely expressed on immune and non-hematopoietic cells. By converting NAD to ADP-ribose and...
The functionally pleiotropic ectoenzyme CD38 is a glycohydrolase widely expressed on immune and non-hematopoietic cells. By converting NAD to ADP-ribose and nicotinamide, CD38 governs organismal NAD homeostasis and the activity of NAD-dependent cellular enzymes. CD38 has emerged as a major driver of age-related NAD decline underlying adverse metabolic states, frailty and reduced health span. CD38 is upregulated in systemic sclerosis (SSc), a chronic disease characterized by fibrosis in multiple organs. We sought to test the hypothesis that inhibition of the CD38 ecto-enzymatic activity using a heavy-chain monoclonal antibody Ab68 will, via augmenting organismal NAD, prevent fibrosis in a mouse model of SSc characterized by NAD depletion. Here we show that treatment of mice with a non-cytotoxic heavy-chain antibody that selectively inhibits CD38 ectoenzyme resulted in NAD boosting that was associated with significant protection from fibrosis in multiple organs. These findings suggest that targeted inhibition of CD38 ecto-enzymatic activity could be a potential pharmacological approach for SSc fibrosis treatment.
Topics: Mice; Animals; ADP-ribosyl Cyclase 1; Antigens, CD; Antigens, Differentiation; NAD+ Nucleosidase; NAD; ADP-ribosyl Cyclase; Membrane Glycoproteins; Glycoside Hydrolases; Fibrosis
PubMed: 38086958
DOI: 10.1038/s41598-023-49450-1 -
Diagnosis (Berlin, Germany) Jun 2017
Topics: Aged, 80 and over; B-Lymphocytes; Female; Humans; Immunoglobulin A; Immunoproliferative Small Intestinal Disease; Intestinal Neoplasms; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma
PubMed: 29536914
DOI: 10.1515/dx-2017-0004 -
Journal of Neurophysiology Mar 2022Neuroaxonal damage is a feature of various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Phosphorylated neurofilament heavy chain (pNfH) is a... (Meta-Analysis)
Meta-Analysis Review
Neuroaxonal damage is a feature of various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Phosphorylated neurofilament heavy chain (pNfH) is a cytoskeletal structural protein released as a result of axonal damage into the cerebrospinal fluid (CSF), and subsequently into the blood. Due to high specificity for neuronal cell damage, pNfH is advantageous over other biomarkers, for ALS disease identification. Here, we review the structure and function of neurofilaments and their role in detection of various neurodegenerative conditions. In addition, a retrospective meta-analysis was performed to depict the significance of pNfH as a valuable diagnostic and prognostic biomarker in ALS.
Topics: Amyotrophic Lateral Sclerosis; Biomarkers; Humans; Intermediate Filaments; Neurofilament Proteins; Retrospective Studies
PubMed: 35138963
DOI: 10.1152/jn.00398.2021 -
Cancer Treatment and Research 2015Marginal zone lymphomas (MZL) represent around 8 % of all non-Hodgkin lymphomas. During the last decades a number of studies have addressed the mechanisms underlying the... (Review)
Review
Marginal zone lymphomas (MZL) represent around 8 % of all non-Hodgkin lymphomas. During the last decades a number of studies have addressed the mechanisms underlying the disease development. Extranodal MZL lymphoma usually arises in mucosal sites where lymphocytes are not normally present from a background of either autoimmune processes, such as Hashimoto thyroiditis or Sjögren syndrome or chronic infectious conditions. In the context of a persistent antigenic stimulation, successive genetic abnormalities can progressively hit a B-cell clone among the reactive B-cells of the chronic inflammatory tissue and give rise to a MALT lymphoma. The best evidence of an etiopathogenetic link is available for the association between Helicobacter pylori-positive gastritis and gastric MALT lymphoma. Indeed, a successful eradication of this micro-organism with antibiotics can be followed by gastric MALT lymphoma regression in more than 2/3 of cases. Other microbial agents have been implicated in the pathogenesis of MZL arising in the skin (Borrelia burgdorferi), in the ocular adnexa (Chlamydophila psittaci), and in the small intestine (Campylobacter jejuni). The prevalence of hepatitis C virus (HCV) has also been reported higher in MZL patients (particularly of the splenic type) than in the control population, suggesting a possible causative role of the virus. In non-gastric MALT lymphoma and in splenic MZL the role of the antimicrobial therapy is, however, less clear. This review summarizes the recent advances in Marginal Zone Lymphomas, addressing the critical points in their diagnosis, staging and clinical management.
Topics: Anti-Bacterial Agents; Humans; Immunoproliferative Small Intestinal Disease; Lymphoma, B-Cell, Marginal Zone; Skin Neoplasms; Stomach Neoplasms
PubMed: 25655612
DOI: 10.1007/978-3-319-13150-4_9 -
Frontiers in Immunology 2020Chromosomal translocations linking various oncogenes to transcriptional enhancers of the immunoglobulin heavy chain (IgH) locus are often implicated as the cause of... (Review)
Review
Chromosomal translocations linking various oncogenes to transcriptional enhancers of the immunoglobulin heavy chain (IgH) locus are often implicated as the cause of B-cell malignancies. Two major IgH transcriptional enhancers have been reported so far. The E enhancer located upstream of the C gene controls early events in B-cell maturation such as VDJ recombination. The 3' regulatory region (3'RR) located downstream from the C gene controls late events in B-cell maturation such as IgH transcription, somatic hypermutation, and class switch recombination. Convincing demonstrations of the essential contributions of both E and 3'RR in B-cell lymphomagenesis have been provided by transgenic and knock-in animal models which bring the oncogene under E/3'RR transcriptional control. This short review summarizes the different mouse models so far available and their interests/limitations for progress in our understanding of human -induced B-cell lymphomagenesis.
Topics: Animals; Disease Models, Animal; Enhancer Elements, Genetic; Gene Expression Regulation, Neoplastic; Genes, myc; Humans; Immunoglobulin Heavy Chains; Lymphoma, B-Cell; Mice; Proto-Oncogene Proteins c-myc; Translocation, Genetic
PubMed: 32793219
DOI: 10.3389/fimmu.2020.01564 -
CEN Case Reports Nov 2014We report a case of probable light- and heavy-chain deposition disease (LHCDD) in a diabetic patient, a rare and educational case. The patient was a 71-year-old man...
We report a case of probable light- and heavy-chain deposition disease (LHCDD) in a diabetic patient, a rare and educational case. The patient was a 71-year-old man having a long history of uncontrolled diabetes mellitus with retinopathy. He showed heavy proteinuria and renal insufficiency, and did not have paraproteins. Renal biopsy revealed nodular glomerulosclerosis with severe mesangial widening and microaneurysm. Immunofluorescence (IF) showed weak staining of kappa light chain, IgG and C1q along glomerular basement membrane (GBM). At first, we interpreted these IF findings to be nonspecific, thus we diagnosed as diabetic nodular glomerulosclerosis. Later, we recognized one of a few case reports of monoclonal immunoglobulin deposition disease (MIDD) in diabetic patients, and reconsidered the first diagnosis. The added electron microscopy (EM) showed obvious electron-dense materials in GBM, while tubular basement membrane deposits were not identified. A concurrence of LHCDD and diabetic nodular glomerulosclerosis may be suggested in this case. Like this case, IF staining in MIDD is often weak, so it is difficult to diagnose MIDD accurately without EM. Reports of MIDD in diabetic patients are extremely rare, possibly due to being often overlooked. This case emphasizes that overall pathological examination including IF and EM is important for the accurate differentiation of nodular glomerulosclerosis, even in diabetic patients.
PubMed: 28509191
DOI: 10.1007/s13730-014-0110-9