Immune-mediated chorea in a patient with kappa light-chain monoclonal gammopathy

Monoclonal gammopathy of undetermined significance (MGUS) has been most commonly associated with diseases like multiple myeloma, Waldenstrom's macroglobulinemia, primary systemic amyloidosis, HIV, and other lymphoproliferative disorders. There has been an isolated report of MGUS in patients coinfected with HIV and Hepatitis B, as the work by Amara et al. in 2006. Here, we report a case of IgA-kappa light chain gammopathy secondary to Hepatitis B infection, which resolved after liver transplantation. To our knowledge, this is the first reported case of M protein spike seen in the context of Hepatitis B infection only.

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Immunoglobulin-Storing Histiocytosis: A Case Based Systemic Review

Journal of Clinical Medicine ◽

10.3390/jcm10091834 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1834

Author(s):

Hanne Wiese-Hansen ◽

Friedemann Leh ◽

Anette Lodvir Hemsing ◽

Håkon Reikvam

Keyword(s):

Light Chain ◽

Monoclonal Gammopathy ◽

Rare Event ◽

Systemic Review ◽

Kappa Light Chain ◽

Disease Entity ◽

Gi Tract ◽

Sex Distribution ◽

Organ Systems ◽

Cell Disorder

Crystal-storing histiocytosis (CSH) is a rare event in disorders associated with monoclonal gammopathy and is mostly associated with the accumulation of immunoglobulins (Igs) in the cytoplasm of histiocytes. In this article, we present a case of a 75-year-old female with IgG kappa monoclonal gammopathy of undetermined significance (MGUS) and signs of a non-crystallized version of immunoglobulin-storing histiocytosis (IgSH) in a vertebra corpus. Furthermore, we performed a literature review based on all cases of storing histiocytosis identified by literature search between 1987 and 2020 and identified 140 cases in total. The median age at diagnosis was 60 years (range 18–91), with an equal sex distribution (51% men). The majority of the patients had an underlying neoplastic B-cell disorder, most often multiple myeloma (MM), MGUS, or lymphoplasmacytic lymphoma (LPL). The main affected organ systems or tissue sites were bone (n = 52), followed by head and neck (n = 31), kidney (n = 23), lung (n = 20), and gastrointestinal (GI)-tract (n = 18). IgG was the main immunoglobulin class involved, and most cases were associated with kappa light chain expression. We conclude that IgSH is a rare disease entity but should be considered with unusual findings in several organ systems associated with monoclonal gammopathy, especially with kappa light chain expression.

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Association of kappa light chain restriction with peripheral neuropathy among patients with non-IgM monoclonal gammopathy of undetermined significance.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e20040 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e20040-e20040

Author(s):

Constantin A. Dasanu ◽

Jaspreet Kaur ◽

Shahaf Tuler ◽

Stephanie Farrell ◽

Steven C. Plaxe

Keyword(s):

Statistical Analysis ◽

Peripheral Neuropathy ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Chronic Inflammatory Demyelinating Polyneuropathy ◽

Axonal Neuropathy ◽

Kappa Light Chain ◽

Related Factors ◽

Study Population ◽

Undetermined Significance

e20040 Background: Monoclonal gammopathy of undetermined significance (MGUS) can be associated with significant neurologic morbidity. Of non-IgM MGUS, types IgG and IgA are most commonly associated with peripheral neuropathy (PN). Methods: With IRB approval, we conducted a retrospective cohort study of consecutive patients with non-IgM type MGUS treated at our institution from 2014-2021. Other conditions potentially causing PN were excluded. Statistical analysis: Descriptive statistics were calculated to characterize the study population, and Relative Risk (RR) of PN was evaluated for selected patient, and disease, related factors. P < 0.05 was defined as statistically significant. Results: During the study period, 94 patients with non-IgM type MGUS were seen and comprised the study population. Twenty-two (23.4%) had evidence of PN. Median age was 74; 82% (18/22 ) were Caucasian; 73% (16/22) were women. 82% (18/22) patients had MGUS type IgG kappa or IgA kappa. We identified only 2 patients with each MGUS kappa light chain (LC) and MGUS IgG lambda. Median M-protein size was 0.11 g/dL, and median free LC value was 6.84 mg/L. Incidence/severity of kidney disease was similar in non-IgM MGUS patients with and without PN (p > 0.05). RR of PN was not found to be significantly different based on race or gender, although there appeared to be a tendency for women to be at higher risk compared to men (RR = 1.98, 95% CI = 0.85 to 4.60, p = 0.114.) Kappa LC restriction was strongly associated with PN (RR = 4.31, 95% CI = 1.58 to 11.78; p = 0.004). Electromyographic (EMG) studies identified 14 patients (64%) with distal symmetric axonal neuropathy (DSAN) and 8 patients (36%) with chronic inflammatory demyelinating polyneuropathy (CIDP). Clinically severe PN was identified in 11 (50%) patients; all were subsequently treated with IVIg therapy. Only 5/11 (45%) patients responded to IVIg, and the responses were only partial and transient. Conclusions: This is the first report, to our knowledge, of a significant association of kappa (as opposed to lambda) LC restriction with PN among patients with non-IgM type MGUS. Further investigation is warranted to explain this finding, elucidate pathophysiology and aid in developing more effective therapeutic options. Pending mechanistic characterization of this association, trials of contemporary agents used to treat other plasma cell disorders may be in order. Final statistical analysis, comparison to published series and significance will be presented.

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Monoclonal Gammopathy of Undetermined Significance with an IgE Paraprotein.

Blood ◽

10.1182/blood.v110.11.4744.4744 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4744-4744

Author(s):

Robert M. Ayto ◽

Christopher Lambert ◽

Irvin Lampert ◽

Nina Salooja

Keyword(s):

Bone Marrow ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Plasma Cells ◽

Bone Marrow Examination ◽

Transformation Rate ◽

Kappa Light Chain ◽

Literature Report ◽

Light Chain Restriction ◽

Co Morbidity

Abstract Monoclonal Gammopathy of Unknown Significance (MGUS) is a non-malignant condition characterized by a serum paraprotein, low numbers of plasma cells on bone marrow examination(<10%) and the absence of end organ damage. The transformation rate of MGUS to multiple myeloma is frequently quoted as about 1% per year. IgG, IgM and IgA paraproteins account for virtually all cases of MGUS with only the rare literature report of IgD or IgE isotypes. To our knowledge there is only one published case of IgE MGUS (Ludwig and Vormittag 1980; BMJ, 281:6239, 539–540). IgE Myeloma is an extremely rare entity and reported to have a comparatively poorer prognosis, but the incidence of pre-existing IgE MGUS is unknown. Here we report the case of a 74 year old gentleman with a stable low level IgE paraprotein. The patient presented in March 2003 for investigation of a persistent borderline normocytic anaemia recorded as 13.3g/dl at initial review (lower range of normal 13.5g/dl) with an ESR of 27mm/h. Co-morbidity included hypertension, ischaemic heart disease and hypercholesterolemia but general examination was unremarkable. Screening investigations revealed normal haematinics, renal function and corrected calcium. Analysis of immunoglobulins revealed mild immunoparesis of his IgM titre only (0.33g/l; Reference range 0.5–2.0g/l) and the presence of both a blood and urinary paraprotein. The blood paraprotein was quantified as 3g/l with immunofixation identifying kappa light chain restriction without the presence of one of the commonly encountered heavy chain isotypes (IgG, IgM or IgA). Further probing of the abnormal gamma globulin region revealed the paraprotein to be IgE in isotype. Immunofixation of a spot urine sample revealed kappa light chain restriction with a protein concentration of 0.03g/l. Bone marrow examination demonstrated 1% plasma cells on the aspirate with mild dysplastic change within the erythroid series. Cytogenetics were not performed. The trephine specimen revealed 10% plasma cells with strong immunostaining for IgE, dysplastic features within the megakaryocytic and erythroid lineages together with confirmation of kappa light chain restriction. Interestingly, recent further immunostaining of the original specimen revealed the plasma cells to be CD56-ve but cyclin D1 positive. Skeletal survey was normal. His investigations fulfil the WHO diagnostic criteria for MGUS, although it could be argued that with 10% plasma cells in the trephine biopsy, he could be classified as a borderline smouldering myeloma. Four years later, however, this gentleman remains well on routine follow-up with no evidence of myeloma related organ or tissue impairment. His most recent paraprotein from August 2007 is stable at 4g/l. The reporting of plasma cell dyscrasias with rare immunoglobulin isotypes should be encouraged to contribute to the bank of knowledge of these infrequently encountered entities.

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Kappa light chain restriction correlates with peripheral neuropathy in patients with non‐IgM monoclonal gammopathy of undetermined significance

European Journal Of Haematology ◽

10.1111/ejh.13716 ◽

2021 ◽

Author(s):

Constantin A. Dasanu ◽

Jaspreet Kaur ◽

Stephanie Farrell ◽

Steven C. Plaxe

Keyword(s):

Peripheral Neuropathy ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Kappa Light Chain ◽

Light Chain Restriction ◽

Undetermined Significance

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Development of Renal Failure without Proteinuria in a Patient with Monoclonal Gammopathy of Undetermined Significance: An Unusual Presentation of AL Kappa Amyloidosis

Case Reports in Nephrology ◽

10.1155/2012/573650 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Yijuan Sun ◽

Amarpreet Sandhu ◽

Darlene Gabaldon ◽

Jonathan Danaraj ◽

Karen S. Servilla ◽

...

Keyword(s):

Renal Failure ◽

Renal Biopsy ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Outlet Obstruction ◽

Renal Ultrasound ◽

Al Amyloidosis ◽

Kappa Light Chain ◽

Severe Renal Failure ◽

Undetermined Significance

AL amyloidosis complicating monoclonal gammopathy of undetermined significance (MGUS) has usually a predominant glomerular deposition of lambda light chain. Heavy proteinuria is one of its cardinal manifestations. A 78-year-old man with a 9-year history of IgG kappa light-chain-MGUS and normal urine protein excretion developed severe renal failure. Serum levels of kappa light chain and serum IgG had been stable while proteinuria was absent throughout the nine-year period. For the first eight years, he had stable stage III chronic kidney disease attributed to bladder outlet obstruction secondary to prostatic malignancy. In the last year, he developed progressive serum creatinine elevation, without any increase in the serum or urine levels of paraproteins or any sign of malignancy. Renal ultrasound and furosemide renogram showed no evidence of urinary obstruction. Renal biopsy revealed AL amyloidosis, with reactivity exclusive for kappa light chains, affecting predominantly the vessels and the interstitium. Glomerular involvement was minimal. Melphalan and prednisone were initiated. However, renal function continues deteriorating. Deposition of AL kappa amyloidosis developing during the course of MGUS predominantly in the wall of the renal vessels and the renal interstitium, while the involvement of the glomeruli is minimal, leads to progressive renal failure and absence of proteinuria. Renal biopsy is required to detect both the presence and the sites of deposition of renal AL kappa light chain amyloidosis.

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Inactivation of Nf-κb Pathway by Taxifolin Attenuates Sepsis-Induced Acute Lung Injury

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.18:176-182 ◽

2019 ◽

Vol 18 (2) ◽

pp. 176-182

Author(s):

Chen Weiyan ◽

Deng Wujian ◽

Chen Songwei

Keyword(s):

Acute Lung Injury ◽

B Cells ◽

Lung Injury ◽

Signaling Pathway ◽

Light Chain ◽

Cecal Ligation ◽

Nuclear Factor ◽

Kappa Light Chain ◽

Cecal Ligation And Puncture ◽

Light Chain Enhancer

Acute lung injury is a clinical syndrome consisting of a wide range of acute hypoxemic respiratory failure disorders. Sepsis is a serious complication caused by an excessive immune response to pathogen-induced infections, which has become a major predisposing factor for acute lung injury. Taxifolin is a natural flavonoid that shows diverse therapeutic benefits in inflammation- and oxidative stress-related diseases. In this study, we investigated the role of taxifolin in a mouse model of cecal ligation and puncture-induced sepsis. Cecal ligation and puncture-operated mice presented damaged alveolar structures, thickened alveolar walls, edematous septa, and hemorrhage compared to sham-treated controls. Cecal ligation and puncture mice also showed increased wet-to-dry (W/D) lung weight ratio and elevated total protein concentration and lactate dehydrogenase level in bronchoalveolar lavage fluid. Taxifolin treatment protected animals against sepsis-induced pulmonary damage and edema. Septic mice presented compromised antioxidant capacity, whereas the administration of taxifolin prior to cecal ligation and puncture surgery decreased malondialdehyde concentration and enhanced the levels of reduced glutathione and superoxide dismutase in mice with sepsis-induced acute lung injury. Moreover, cecal ligation and puncture-operated mice showed markedly higher levels of proinflammatory cytokines relative to sham-operated group, while taxifolin treatment effectively mitigated sepsis-induced inflammation in mouse lungs. Further investigation revealed that taxifolin suppressed the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway in cecal ligation and puncture-challenged mice by regulating the phosphorylation of p65 and IκBα. In conclusion, our study showed that taxifolin alleviated sepsis-induced acute lung injury via the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, suggesting the therapeutic potential of taxifolin in the treatment sepsis-induced acute lung injury.

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