scholarly journals Predominant Mesangial IgM, C3 and λ Light Chain Depositions and Interstitial Nephritis in a Patient with Overlap Syndrome and Positivity for Anti-Mitochondrial M2 Antibody: A Case Report

2021 ◽  
Author(s):  
Saeko Yamada ◽  
Hiroko Kanda ◽  
Hiroyuki Abe ◽  
Yukako Shintani Domoto ◽  
Ryochi Yoshida ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Dysfunction ◽  
Interstitial Nephritis ◽  
Light Chain ◽  
Lupus Erythematosus ◽  
Plasma Cells ◽  
Overlap Syndrome ◽  
Pathological Findings ◽  
Glucocorticoid Treatment ◽  
Λ Light Chain

Abstract Overlap syndrome refers to a group of conditions that have clinical features of more than one well-characterized rheumatic disease and meet the respective classification criteria. There are no typical renal histological findings in overlap syndrome. When patients with overlap syndrome develop renal dysfunction, various potential causes, including lupus nephritis (LN), renal crisis by systemic sclerosis, interstitial nephritis and so on, need to be distinguished. Here we report a 44-year-old woman with overlap syndrome involving systemic lupus erythematosus (SLE), diffuse cutaneous systemic scleroderma and Sjogren’s syndrome, who was also positive for anti-mitochondrial M2 antibody. She developed glomerular hematuria, proteinuria and increase in creatinine appeared gradually. Suspecting lupus nephritis, renal biopsy was performed. However, in the interstitium, mild infiltration of lymphocytes and plasma cells and very partial fibrosis were observed. Immunofluorescence (IF) microscopy revealed predominant mesangial IgM, C3 and λ light chain staining. Overall, LN was not diagnosed based on these findings. Renal dysfunction was normalized by glucocorticoid treatment for three months. This case suggests the importance of a renal diagnosis based on renal pathological findings, especially in a case of overlap syndrome including SLE.

scholarly journals The Normal Counterpart of IgD Myeloma Cells in Germinal Center Displays Extensively Mutated IgVH Gene, Cμ–Cδ Switch, and λ Light Chain Expression

1998 ◽  
Vol 187 (8) ◽  
pp. 1169-1178 ◽  
Author(s):  
Christophe Arpin ◽  
Odette de Bouteiller ◽  
Diane Razanajaona ◽  
Isabelle Fugier-Vivier ◽  
Francine Brière ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Light Chain ◽  
Germinal Center ◽  
Plasma Cells ◽  
Precursor Cells ◽  
Memory B Cells ◽  
Hematopoietic Stem ◽  
Myeloma Cells ◽  
Λ Light Chain

Human myeloma are incurable hematologic cancers of immunoglobulin-secreting plasma cells in bone marrow. Although malignant plasma cells can be almost eradicated from the patient's bone marrow by chemotherapy, drug-resistant myeloma precursor cells persist in an apparently cryptic compartment. Controversy exists as to whether myeloma precursor cells are hematopoietic stem cells, pre–B cells, germinal center (GC) B cells, circulating memory cells, or plasma blasts. This situation reflects what has been a general problem in cancer research for years: how to compare a tumor with its normal counterpart. Although several studies have demonstrated somatically mutated immunoglobulin variable region genes in multiple myeloma, it is unclear if myeloma cells are derived from GCs or post-GC memory B cells. Immunoglobulin (Ig)D-secreting myeloma have two unique immunoglobulin features, including a biased λ light chain expression and a Cμ–Cδ isotype switch. Using surface markers, we have previously isolated a population of surface IgM−IgD+CD38+ GC B cells that carry the most impressive somatic mutation in their IgV genes. Here we show that this population of GC B cells displays the two molecular features of IgD-secreting myeloma cells: a biased λ light chain expression and a Cμ–Cδ isotype switch. The demonstration of these peculiar GC B cells to differentiate into IgD-secreting plasma cells but not memory B cells both in vivo and in vitro suggests that IgD-secreting plasma and myeloma cells are derived from GCs.

Light Chain Shifting: Identification of a Human Plasma Cell Line Actively Undergoing Light Chain Replacement

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 198-207 ◽  
Author(s):  
Hirofumi Tachibana ◽  
Hirotaka Haruta ◽  
Koji Yamada
Keyword(s):  
Cell Line ◽  
Human Plasma ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
High Rate ◽  
Cell Phenotype ◽  
Recombination Activating Genes ◽  
Λ Light Chain ◽  
Rag 1

Abstract We identified an antibody-secreting human B-cell line (HTD8), which actively replaces the production of the original λ light chain with a new λ chain (light chain shifting) at a high rate. Loss of the original rearranged λ light chain occurs by significantly reducing the amount of transcript expressed. Expression of the new λ chain, which replaces the original λ chain, occurs by rearranging new VJ segments on a previously excluded allele. V λ gene usage of these new rearrangements are biased toward Vλ4, Vλ6, and Vλ10 families, which are known to be the least frequently used. In striking contrast to the plasma cell phenotype, recombination activating genes, RAG-1 and RAG-2, were expressed in the HTD8 cells and were shown to be necessary, but insufficient for inducing expression of the new λ chain. These results suggest that human plasma cells have the potential to actively undergo light chain replacement.

Restrictive usage of monoclonal immunoglobulin λ light chain germline in POEMS syndrome

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 836-839 ◽  
Author(s):  
Daijiro Abe ◽  
Chiaki Nakaseko ◽  
Masahiro Takeuchi ◽  
Hiroaki Tanaka ◽  
Chikako Ohwada ◽  
...  
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Poems Syndrome ◽  
Monoclonal Immunoglobulin ◽  
Variable Regions ◽  
Plasma Cell Disorder ◽  
Λ Light Chain ◽  
V Region ◽  
Restricted Use ◽  
Endothelial Growth Factor

Abstract POEMS syndrome is a rare plasma cell disorder characterized by peripheral neuropathy, monoclonal gammopathy, and high levels of serum vascular endothelial growth factor, the pathogenesis of which remains unclear. A unique feature of this syndrome is that the proliferating monoclonal plasma cells are essentially λ-restricted. Here we determined complete nucleotide sequences of monoclonal immunoglobulin λ light chain (IGL) variable regions in 11 patients with POEMS syndrome. The V-region of the Igλ gene of all 11 patients was restricted to the Vλ1 subfamily. Searching for homologies with IGL germlines revealed that 2 germlines, IGLV1-44*01 (9/11) and IGLV1-40*01 (2/10), were identified, with an average homology of 91.1%. The IGLJ3*02 gene was used in 11 of 11 re-arrangements with an average homology of 92.2%. These data suggest that the highly restricted use of IGL Vλ1 germlines plays an important role in the pathogenesis of POEMS syndrome.

scholarly journals Systemic lupus erythematosus-myositis overlap syndrome with lupus nephritis

2020 ◽  
Vol 9 (4) ◽  
pp. 2104
Author(s):  
Biswajit Dey ◽  
Vandana Rapahel ◽  
Yookarin Khonglah ◽  
Md Jamil
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Overlap Syndrome ◽  
Systemic Lupus

scholarly journals Biases in Ig λ Light Chain Rearrangements in Human Intestinal Plasma Cells

2004 ◽  
Vol 172 (4) ◽  
pp. 2360-2366 ◽  
Author(s):  
Wen Su ◽  
Laurent Boursier ◽  
Archana Padala ◽  
Jeremy D. Sanderson ◽  
Jo Spencer
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Λ Light Chain

scholarly journals Intermittent Fasting Aggravates Lupus Nephritis through Increasing Survival and Autophagy of Antibody Secreting Cells in MRL/lpr Mice

2020 ◽  
Vol 21 (22) ◽  
pp. 8477
Author(s):  
Seung-Min Hong ◽  
Jaeseon Lee ◽  
Se Gwang Jang ◽  
Youngseok Song ◽  
Minjun Kim ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Lupus Nephritis ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Plasma Cells ◽  
Clinicopathological Parameters ◽  
Control Group ◽  
Intermittent Fasting ◽  
Glomerular Injury ◽  
Dsdna Antibody

Systemic lupus erythematosus (SLE) is an autoimmune disease in which the main contributors to organ damage are antibodies against autoantigens, such as double-stranded DNA (dsDNA). Calorie restriction and intermittent fasting (IF) have been shown to improve autoimmune disease symptoms in patients and animal models. Here, we tested the hypothesis that IF might improve symptoms in MRL/lpr mice, which spontaneously develop an SLE-like disease. Groups of mice were fed every other day (IF) or provided food ad libitum (controls), and various lupus-associated clinicopathological parameters were analyzed for up to 28 weeks. Contrary to expectations, anti-dsDNA antibody levels, immune complex deposition in the kidney, and glomerular injury were higher in the IF group than the control group, although there were no differences in spleen and lymph node weights between groups. Proteinuria was also worsened in the IF group. IF also increased the abundance of B cells, plasmablasts, and plasma cells and elevated autophagy in plasma cells in the spleen and lymph nodes. Secretion of anti-dsDNA antibody by splenocytes in vitro was reduced by chloroquine-induced inhibition of autophagy. These results suggest that IF exacerbates lupus nephritis in MRL/lpr mice by increasing autoantibody immune complex formation.

scholarly journals AB0124 NO EFFECTS OF HIGH DOSE 25OH-VITAMIN D SUPPLEMENTATION ON LUPUS NEPHRITIS IN AN ANIMAL MODEL OF SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1362.2-1362
Author(s):  
S. Barsotti ◽  
C. Tani ◽  
A. Kuhl ◽  
S. Pacini ◽  
S. Vagnani ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Vitamin D ◽  
Animal Model ◽  
Lupus Nephritis ◽  
Interstitial Nephritis ◽  
Lupus Erythematosus ◽  
Statistical Significance ◽  
High Dose ◽  
Systemic Lupus ◽  
Renal Histology

Background:25OH Vitamin D (25-OH-D3) is a fat-soluble steroid-derived molecule involved in the calcium homeostasis. Low levels of 25-OH-D3 are commonly found in patients with systemic lupus erythematosus (SLE) and have been correlated to higher disease activity and severity. Several recent studies have demonstrated that high dose Vitamin D may influence several aspects of the innate and adaptive immune response and some authors hypothesized that high dose 25-OH-D3 may have a role in the treatment of SLE. Despite these observations, the immunomodulatory effect of high dose 25-OH-D3in vivostill needs to be demonstrated.Objectives:The aim of our study was to identify the effect of 25-OH-D3 on proteinuria, survival and renal biopsy in New Zealand Black/White F1 mice (NZ), that develop a disease very similar to human SLE nephritis.Methods:We administered to 20 NZ mice a diet enriched with high dose 25-OH-D3 10,000 UI/Kg starting from 8 weeks of age. Mice were divided in 7 experimental groups (5 mice each). The first group was sacrificed before the start of the treatment (8 week of age), three groups were treated (treated mice – TM) with 25-OH-D3 and sacrificed at 16, 26 and 36 weeks of age. The other three groups were enrolled as controls and sacrificed at 16, 26 and 36 weeks of age respectively (untreated mice – UM). The parameters collected included: total urinary protein and kidney histology for the evaluation of lupus nephritis (LN): glomerulonephritis, interstitial nephritis and vascular lesions according to a 5 points scale to obtain a total score (ranging from 0 to 12).Results:In UM, proteinuria tended to increase over 1 mg/day at 12 weeks of age (1.7±0.43mg/day) and further increased until to reach a plateau after 28 weeks of age (10±2.0 mg/day).In TM, a significant increase in proteinuria over 1 mg/day was observed at 24 weeks, when the mean proteinuria was 1.7±1.33 which was lower than controls at the same age although without statistical significance (2.9±2.6); thereafter proteinuria started to increase also in treated mice and at week 30 was higher in TM compared with UM (10,3±8.8 vs 4.3±3.5 p=0.05). Figure 1.Kidney histology showed, in mice sacrificed before the start of the treatment no signs of LN. In mice sacrificed at 16 weeks minimal interstitial nephritis (score 1) was identified in 2 mice only in UM. At 26 weeks of age, a higher total LN score was identified in TM compared with UM (3.4±3.8 vs 0.4 ±0.9) with higher score for all three parameters analyzed. At 36 weeks of age, the TM group maintained a higher total LN score compared to UM (6.5±1.7 vs 6.0±2.6) with higher score for glomerulonephritis and interstitial nephritis.In the TM group, three mice spontaneously died at 26, 30 and 32 weeks of age, while in the UM only one mouse died at 36 weeks of age.Conclusion:Our data suggest that, in this animal model of SLE, 25-OH-D3 administration seems to delay the onset of proteinuria, although has no effect on the overall disease control. In addition, it may have a negative effect on renal histology and survival with earlier development of LN.Figure:Disclosure of Interests:None declared

scholarly journals Bullous Systemic Lupus Erythematosus and Membranous Lupus Nephritis in a Filipino Child

2019 ◽  
Vol 53 (1) ◽  
Author(s):  
Marc Andrew O. Perez ◽  
Candice B. Brillante ◽  
Lourdes Paula R. Resontoc ◽  
Dolores D. Bonzon ◽  
Francisco E. Anacleto ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Basement Membrane ◽  
Lupus Erythematosus ◽  
Plasma Cells ◽  
Kidney Biopsy ◽  
Direct Immunofluorescence ◽  
Systemic Lupus ◽  
Cutaneous Manifestations ◽  
Membranous Lupus Nephritis

Bullous eruptions are rare cutaneous manifestations of systemic lupus erythematosus. We report a case of an 8-year old Filipino girl with vesiculobullous systemic lupus erythematosus (SLE) and membranous lupus nephritis on kidney biopsy who presented with clinical nephrotic features of generalized edema, proteinuria, hypoalbuminemia and hyperlipidemia. The 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE were met. Immunohistopathologic examination of the skin lesion revealed a sub-epidermal split with neutrophilic infiltrates along the dermo-epidermal junction, moderate perivascular, periadnexal and interstitial infiltrates composed of predominantly neutrophils with neutrophilic dusts, lymphocytes, plasma cells, rare eosinophils and increased dermal mucin. Direct immunofluorescence showed strong continuous linear IgG deposits along the basement membrane and weak linear IgM and IgA deposition along the basement membrane zone (BMZ). To our knowledge, this is the first report of vesiculobullous SLE in a Filipino child. This case is a rare form of cutaneous lupus in children. Bullous SLE (BSLE) should be considered in the differential diagnosis of children presenting with generalized bullous eruptions.

Light Chain Shifting: Identification of a Human Plasma Cell Line Actively Undergoing Light Chain Replacement

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 198-207
Author(s):  
Hirofumi Tachibana ◽  
Hirotaka Haruta ◽  
Koji Yamada
Keyword(s):  
Cell Line ◽  
Human Plasma ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
High Rate ◽  
Cell Phenotype ◽  
Recombination Activating Genes ◽  
Λ Light Chain ◽  
Rag 1

We identified an antibody-secreting human B-cell line (HTD8), which actively replaces the production of the original λ light chain with a new λ chain (light chain shifting) at a high rate. Loss of the original rearranged λ light chain occurs by significantly reducing the amount of transcript expressed. Expression of the new λ chain, which replaces the original λ chain, occurs by rearranging new VJ segments on a previously excluded allele. V λ gene usage of these new rearrangements are biased toward Vλ4, Vλ6, and Vλ10 families, which are known to be the least frequently used. In striking contrast to the plasma cell phenotype, recombination activating genes, RAG-1 and RAG-2, were expressed in the HTD8 cells and were shown to be necessary, but insufficient for inducing expression of the new λ chain. These results suggest that human plasma cells have the potential to actively undergo light chain replacement.

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