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

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.

scholarly journals Hepatitis B Associated Monoclonal Gammopathy That Resolved after Successful Liver Transplant

2009 ◽  
Vol 2009 ◽  
pp. 1-3
Author(s):  
P. Sreenivasan ◽  
S. Nair
Keyword(s):  
Multiple Myeloma ◽  
Liver Transplantation ◽  
Hepatitis B ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Lymphoproliferative Disorders ◽  
M Protein ◽  
Kappa Light Chain ◽  
Hepatitis B Infection ◽  
Undetermined Significance

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.

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

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
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.

scholarly journals Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study

Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5412-5417 ◽  
Author(s):  
Ola Landgren ◽  
Robert A. Kyle ◽  
Ruth M. Pfeiffer ◽  
Jerry A. Katzmann ◽  
Neil E. Caporaso ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Population Based ◽  
Serum Samples ◽  
M Proteins ◽  
Cancer Screening Trial ◽  
Risk Of Progression ◽  
Study Population ◽  
A Prospective Study ◽  
Undetermined Significance

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma-cell proliferative disorder associated with a life-long risk of progression to multiple myeloma (MM). It is not known whether MM is always preceded by a premalignant asymptomatic MGUS stage. Among 77 469 healthy adults enrolled in the nationwide population-based prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we identified 71 subjects who developed MM during the course of the study in whom serially collected (up to 6) prediagnostic serum samples obtained 2 to 9.8 years prior to MM diagnosis were available. Using assays for monoclonal (M)–proteins (electrophoresis/immunofixation) and kappa-lambda free light chains (FLCs), we determined longitudinally the prevalence of MGUS and characterized patterns of monoclonal immunoglobulin abnormalities prior to MM diagnosis. MGUS was present in 100.0% (87.2%-100.0%), 98.3% (90.8%-100.0%), 97.9% (88.9%-100.0%), 94.6% (81.8%-99.3%), 100.0% (86.3%-100.0%), 93.3% (68.1%-99.8%), and 82.4% (56.6%-96.2%) at 2, 3, 4, 5, 6, 7, and 8+ years prior to MM diagnosis, respectively. In approximately half the study population, the M-protein concentration and involved FLC-ratio levels showed a yearly increase prior to MM diagnosis. In the present study, an asymptomatic MGUS stage consistently preceded MM. Novel molecular markers are needed to better predict progression to MM in patients with MGUS.

scholarly journals Prevalence of Monoclonal Gammopathy of Undetermined Significance in a Large Population with Annual Physical Examination in Beijing, China

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5519-5519
Author(s):  
Jinuo Wang ◽  
Jian-Hua Han ◽  
Yue-lun Zhang ◽  
Xin-xin Cao ◽  
Dao-Bin Zhou ◽  
...  
Keyword(s):  
Physical Examination ◽  
Light Chain ◽  
Chinese Population ◽  
Monoclonal Gammopathy ◽  
Conflicts Of Interest ◽  
Large Population ◽  
M Protein ◽  
Monoclonal Protein ◽  
Significant Difference ◽  
Undetermined Significance

Introduction Monoclonal gammopathy of undetermined significance (MGUS) is a clinically asymptomatic premalignant plasma cell disorder. Previous studies in Western countries have described the prevalence of MGUS in Caucasians. However, data is limited in Chinese population. We therefore performed this study to ascertain the prevalence and characteristics of MGUS among Chinese population. Methods A total of 154597 consecutive healthy participants from Beijing who underwent annual physical examination between December 2013 and April 2019 at Peking Union Medical College Hospital were enrolled. Serum M protein was evaluated by capillary electrophoresis. Patients with a positive or suspicious serum M protein were suggested to be referred to the hematological clinic for immunofixation electrophoresis (IFE) and free light chain (FLC) assays. MGUS was defined in accordance with previous definitions. We calculated age-specific and sex-specific prevalence and described laboratory characteristics of patients with MGUS among those participants. Results MGUS were diagnosed in 843 patients (0.55%, 95%CI 0.51% to 0.59%). The median age at presentation was 58 years, with a range of 25-96 years. The overall prevalence of MGUS was 1.14% among participants aged 50 years or older and 2.6% among those aged 70 years or older. In both sexes, the prevalence increased with age: 0.1% (<40 years), 0.36% (40-49 years), 0.78% (50-59 years), 1.28% (60-69 years), 2.19% (70-79 years), and 3.77% (≥80 years) separately (Figure 1). The prevalence among men were higher than that among women (0.67% vs. 0.40%, OR =1.719, 95% CI 1.490 to 1.983, P<0.001) (Figure 1). The median concentration of serum Monoclonal protein was 1.4 g/L (0.1 -27.8 g/L). M protein level was less than 0.5g/L in 220 patients (26.1%), less than 5 g/L in 81.1% and more than 15 g/L in only 1.9% of 843 persons. There was no significant difference in the concentration of the monoclonal protein among the age groups. Of the 519 patients who were tested for IFE, the isotype of the monoclonal immunoglobulin was IgG in 344 (66.3%), IgA 112 (21.6%), IgM in 48 (9.2%), IgD in 2 (0.4%), light-chain in 3 (0.6%) and biclonal in 10 (1.9%). The serum light-chain type was kappa in 260 (50.1%), lambda in 255 (49.1%) patients, while 4 patients (0.8%) with biclonal M protein have both kappa and lambda light-chain. Of the 180 people who were tested for FLC, 42 (23.3%) had an abnormal FLC ratio. IgG isotype, M protein <15 g/L and normal FLC ratio were found in 102 patients (56.7%) and the remaining 78 people (43.4%) had 1(30.6%) or 2(12.8%) abnormal factors. Conclusions MGUS was found in 1.14% of persons 50 years of age or older and 2.6% among those 70 years of age or older among healthy Chinese population. The prevalence of MGUS increases with age. Males have a higher frequency of MGUS than Females. These observations offer the overall situation of MGUS epidemiology in a large Chinese population. Disclosures No relevant conflicts of interest to declare.

A 68-Year-Old Male with Progressive Numbness and Gait Difficulties

2016 ◽  
Author(s):  
Jeffrey A. Cohen ◽  
Justin J. Mowchun ◽  
Victoria H. Lawson ◽  
Nathaniel M. Robbins
Keyword(s):  
Peripheral Neuropathy ◽  
Monoclonal Gammopathy ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Peripheral Neuropathies ◽  
Hematologic Disease ◽  
Monoclonal Protein ◽  
Inflammatory Demyelinating Polyneuropathy ◽  
Management Approaches ◽  
Hematological Evaluation

Paraproteinemic demyelinating peripheral neuropathies require specific diagnostic and management approaches. The clinical features as well as the type of monoclonal protein and possible associated antibodies are all important considerations in evaluation and management of these complex presentations. It is important to recognize anti-myelin associated glycoproteins positive peripheral neuropathy, which is associated with IgM gammopathy, and typically presents with a sensory ataxia. Hematologic disease may mimic chronic inflammatory demyelinating polyneuropathy. This chapter also describes the role of hematological evaluation for patients with peripheral neuropathy and a monoclonal gammopathy.

Light Chain Predominant Intact Immunoglobulin Monoclonal Gammopathy Disorders: Shorter Survival in Light Chain Predominant Multiple Myelomas

2020 ◽  
Author(s):  
Gurmukh Singh ◽  
Hongyan Xu
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Change Point ◽  
Monoclonal Gammopathy ◽  
Biological Significance ◽  
Data Set ◽  
Serum Free ◽  
Associated Lesions ◽  
Multiple Myelomas ◽  
Undetermined Significance

Abstract Background A proportion of intact immunoglobulin (Ig)–producing multiple myelomas (MMs) was observed to secrete much higher amounts of free light chains (LCs) than usual. Objectives To determine the change point between usual and LC-predominant intact Ig-secreting MMs and other monoclonal gammopathic manifestations and the biological significance of the observation. Methods We conducted retrospective examination of laboratory findings in 386 MM, 27 smoldering MM, and 179 monoclonal gammopathy of undetermined significance (MGUS) cases that secreted intact Igs. We recorded the highest levels of involved serum free LC, highest ratio of involved to uninvolved LC, highest concentration of involved LC per g of monoclonal Ig, and highest value for ratio of involved to uninvolved LCs divided by the monoclonal Ig concentration. Each data set was sorted into kappa- and lambda LC-associated lesions. Length of time, in months, between diagnosis and last contact with the patients having myeloma was recorded. Results Change point analysis of data revealed a subgroup of cases with distinctly higher levels of free LCs. In myelomas, including plasma cell leukemias, 16.4% of myelomas with kappa LCs and 22.3% of myelomas with lambda LCs, the LC secretion was distinctly higher than in the remaining cases, by a combination of 4 parameters, listed herein. Corresponding figures for smoldering myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS) were 12.5, 27.3, 3.8, and 6.8, respectively. Ten of the 13 (77%) cases of plasma cell leukemia) and all cases of IgD myeloma (n = 4) showed excess secretion of serum free LCs. Among IgG and IgA myelomas, including plasma cell leukemias, the LC-predominant lesions had shorter survival, by an average of 22.5 months. Conclusions In total, 18.4% of MMs, including plasma cell leukemias, secrete distinctly higher amounts of serum free LCs than other intact Ig-secreting myelomas and confer significantly lower survival. Quantification of monoclonal serum free LCs may be useful in this subgroup in monitoring progress and potentially in ascertaining minimal residual disease. The findings also stress the need for separate criteria for kappa and lambda LC associated monoclonal gammopathic manifestations. The significantly shorter survival of patients with LC-predominant myelomas warrants consideration in prospective trials of treatments.

Seeking Diagnostic Confidence in Typing Amyloidosis: Prospective Results with an Algorithm To Minimize Misdiagnosis of Immunoglobulin Light-Chain (AL) Amyloidosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5099-5099
Author(s):  
Raymond L. Comenzo ◽  
Ping Zhou ◽  
Limin Wang ◽  
Bradly D. Clark ◽  
Martin Fleisher ◽  
...  
Keyword(s):  
African American ◽  
Peripheral Neuropathy ◽  
African Americans ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Cardiac Amyloid ◽  
Hereditary Amyloidosis ◽  
The Usa

Abstract In order to treat patients with symptomatic amyloidosis, the amyloidosis must be typed with confidence. Immunohistochemical techniques for light-chain isotype identification of amyloid are not reliable, and techniques to type fibrils extracted from clinical specimens are neither widely available nor validated. Retrospectively, investigators in the United Kingdom have shown that hereditary amyloidosis can be misdiagnosed as AL in 10% of cases because family history is often not relevant and because a monoclonal gammopathy (MG) and an hereditary variant can be present in the same patient (NEJM2002;346). The most common types of amyloidosis in the USA are AL and hereditary, the latter due to mutations in proteins such as transthyretin (TTR), fibrinogen A α-chain (FnAα), apolipoprotein AI or AII, and lysozyme. The genes for these proteins are not routinely examined in all cases of likely AL amyloidosis, and clinical genetics laboratories do not offer screening for all of them. The most common hereditary variant in the USA is the V122I transthyretin mutation found in 4% of African-Americans. In addition, a common presentation of both AL and hereditary amyloidosis is peripheral neuropathy. Furthermore, in the case of FnAα nephropathy, patients usually have isolated renal amyloid without marrow involvement. To minimize the risk of misdiagnosis of AL at our center, we prospectively tested four categories of patients with a tissue diagnosis of amyloidosis for hereditary variants whether or not MG was present: African-Americans, patients with dominant peripheral neuropathy (PN), patients with isolated renal amyloidosis (RA) without marrow involvement, and patients referred for hereditary testing or lack of MG. Testing was by PCR amplification and sequencing of genomic DNA. From 6/1/02 to 8/1/05, we evaluated 178 patients referred for amyloidosis, and 30% (n=54) were screened according to this algorithm: 20 African-Americans (16 with MG), 16 with PN (11 with MG), 7 with RA without marrow amyloid (all with MG), 7 referred for hereditary testing and 4 without MG. Of those with amyloidosis and monoclonal gammopathies, 6% (2/34) had both a monoclonal gammopathy and heterozygosity for a mutant TTR: a 45 year-old African-American man (V122I) with cardiac amyloid and a 59 year-old man (F64L) with polyneuropathy. Of the 9 African-American and PN patients without MG, 4 had mutant TTR. Of 7 sent for hereditary testing, 6 had mutant TTR, one of whom also was found to have undiagnosed stage I lambda light-chain myeloma. Of 4 without MG, 2 had senile cardiac amyloid, 1 AA and 1 had amyloid that could not be typed. For those with mutant TTR and MG, TTR tissue-staining resolved the type of amyloid. These results justify further study of screening for hereditary variants in patients with apparent AL, including those with AL associated with multiple myeloma. Myelotoxic therapies such as stem cell transplant are not appropriate treatments for patients with hereditary amyloidosis. These results also highlight the need for the development, validation and dissemination of reliable techniques for identifying fibrils extracted from tissue, and raise the question as to whether or not hereditary amyloid proteins increase the risk of developing MG.

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