77:. The variable (V) domain of light chains has a high degree of structural diversity, particularly the antigen-binding region. In addition, the first 23 amino acids of the 1st variable domain framework region have a number of variations known as subgroups. Four kappa (Vκ1–Vκ4) and six lambda subgroups (Vλ1–Vλ6) can be identified. The subgroup structures of FLCs influence their ability to polymerize (combine) and form proteins like amyloid fibrils. For example, the Vλ6 subgroup of FLCs is associated with a type of amyloidosis called AL amyloidosis, while the Vκ1 and Vκ4 subgroups are associated with a different type of amyloidosis called light-chain deposition disease.
170:" or "myeloma kidney" and is typically found in patients with multiple myeloma. This can block the flow of urine causing the death of the respective nephrons. Rising concentrations of light chains are filtered by the remaining nephrons leading to a cycle of accelerating renal damage with rising concentrations of free light chains in the blood. At the same time, the amount of free light chains entering the urine will be decreased and will be zero if the patient stops producing urine (
102:
proper structure of the intact immunoglobulin molecules, but it is also possible that free light chains have an immunological function. There are approximately twice as many kappa-producing plasma cells as lambda plasma cells. Kappa free-light chains are normally monomeric, while lambda free-light chains tend to be dimeric, joined by disulphide bonds. Polymeric forms of both types of free light chain can also occur.
190:
of the re-absorption of free light chains in the kidneys, creating a threshold of light chain production which must be exceeded before measurable quantities overflow into the urine. While there are a number of publications indicating that serum free light chain analysis is preferable to urine analysis at diagnosis, there is currently no consensus on whether urine tests for monitoring should be replaced.
189:
Serum free light-chain assays have been used in a number of published studies which have indicated superiority over the urine tests, particularly for patients producing low levels of monoclonal free light chains, as seen in nonsecretory multiple myeloma and AL amyloidosis. This is primarily because
101:
The production of free immunoglobulin light chains in normal individuals is approximately 500 mg/day from bone marrow and lymph node cells. The production of immunoglobulin light chains is about 40% greater than the production of immunoglobulin heavy chains. This may simply be to allow for the
246:
Serial serum free light-chain measurement should be routinely performed in patients with AL amyloidosis and multiple myeloma patients with oligosecretory disease. It should also be done in all patients who have achieved a complete response to treatment to determine whether they have attained a
110:
In normal individuals, free light chains are rapidly cleared from the blood and catabolised by the kidneys. Monomeric free light chains are cleared in 2–4 hours, and dimeric light chains in 3–6 hours. Removal may be prolonged to 2–3 days in people with complete renal failure. Human kidneys are
85:
Kappa light-chain molecules are constructed from approximately 40 functional Vκ gene segments (chromosome 2), five Jκ gene segments and a single Cκ gene. Lambda molecules (chromosome 22) are constructed from about 30 Vλ gene segments and four pairs of functional Jλ gene segments and a Cλ gene.
2207:
Gertz MA, Comenzo R, Falk RH, et al. (August 2005). "Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): A consensus opinion from the 10th
International Symposium on Amyloid and Amyloidosis, Tours, France, 18–22 April 2004".
181:, however, flows through the glomeruli and is completely processed by the proximal tubules. If the proximal tubules of the nephrons are damaged or stressed (such as in hard exercise), filtered FLCs may not be completely metabolised and small amounts may then appear in the urine.
174:). Conversely, urine concentrations of free light chains could increase if renal function improved in a multiple myeloma patient receiving treatment. This could account for the poor correlation frequently seen when urine and serum free light-chain concentrations are compared.
52:
are immunoglobulin light chains that are found in the serum (blood) in an unbound (free) state. In recent decades, measuring the amount of free light chains (FLCs) in the blood has become a practical clinical test. FLC tests can be used to diagnose and monitor diseases like
145:
If immunoglobulin light chains are produced in sufficient amounts to overwhelm the proximal tubules' absorption mechanisms (usually due to the presence of a plasma cell tumour) the light chains enter the distal tubules and can appear in the urine
142:) and prevents the loss of large amounts of protein into the urine. It is very efficient and can process 10–30 g of low-molecular-weight proteins per day, so under normal conditions no light chains pass beyond the proximal tubules.
1229:
Drayson M, Tang LX, Drew R, Mead GP, Carr-Smith H, Bradwell AR, Tang, Drew, Mead, Carr-Smith, Bradwell (May 2001). "Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma".
1649:
Katzmann JA, Dispenzieri A, Kyle RA, et al. (December 2006). "Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays".
165:
of 20–30 molecules. It contains a short amino-acid sequence that can specifically bind to some free light chains. Together they can form an insoluble precipitate which blocks the distal part of the nephrons. This is termed
2080:
Pratt G, Harding S, Holder R, et al. (January 2009). "Abnormal serum free light chain ratios are associated with poor survival and may reflect biological subgroups in patients with chronic lymphocytic leukaemia".
1384:
Lachmann HJ, Gallimore R, Gillmore JD, et al. (July 2003). "Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy".
237:
electrophoresis is sufficient to screen for pathological monoclonal plasmaproliferative disorders other than AL amyloidosis which requires all the serum tests as well as 24 h urine immunofixation electrophoresis.
250:
Other guidelines for the use of serum free light chain measurement in the management of AL amyloidosis, plasmacytoma and the comparison of treatment responses in clinical trials have also been published.
69:
Each immunoglobulin light-chain molecule contains approximately 220 amino acids in a single polypeptide chain that is folded to form constant and variable region domains. Each domain comprises two
93:
development and are expressed initially on the surface of pre B-cells. Production of light chains occurs throughout the rest of B-cell development and in plasma cells, where secretion is highest.
161:). This is the dominant protein in normal urine and is thought to be important in preventing ascending urinary infections. It is a relatively small glycoprotein (80 kDa) that aggregates into
221:
In 2009, the
International Myeloma Working Group published guidelines making recommendations of when serum free light-chain analysis should be used in the management of multiple myeloma.
130:
Filtered molecules are either excreted in the urine or may be specifically re-absorbed. Protein molecules that pass through the glomerular pores are either absorbed unchanged (such as
1134:
Nowrousian MR, Brandhorst D, Sammet C, et al. (December 2005). "Serum free light chain analysis and urine immunofixation electrophoresis in patients with multiple myeloma".
1004:
Bradwell AR, Carr-Smith HD, Mead GP, Harvey TC, Drayson MT, Carr-Smith, Mead, Harvey, Drayson (February 2003). "Serum test for assessment of patients with Bence Jones myeloma".
197:, have indicated that patients with an abnormal free kappa to free lambda ratio have an increased risk of progression to active myeloma from precursor conditions including
401:"The renal handling of low molecular weight proteins: II. Disorders of serum protein catabolism in patients with tubular proteinuria, the nephrotic syndrome, or uremia"
134:), degraded in the proximal tubular cells and absorbed (such as free light chains), or excreted as fragments. This re-absorption is mediated by a receptor complex (
1068:"Free immunoglobulin light-chain serum levels in the follow-up of patients with monoclonal gammopathies: correlation with 24-hr urinary light-chain excretion"
2253:"Guidelines on the diagnosis and management of solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas: 2009 update"
1622:
Abadie JM, Bankson DD, Bankson (2006). "Assessment of serum free light chain assays for plasma cell disorder screening in a
Veterans Affairs population".
1939:
Kyrtsonis MC, Vassilakopoulos TP, Kafasi N, et al. (May 2007). "Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma".
2033:"High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis"
1469:
Akar H, Seldin DC, Magnani B, et al. (December 2005). "Quantitative serum free light chain assay in the diagnostic evaluation of AL amyloidosis".
198:
17:
2252:
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Redegeld FA, Nijkamp FP, Nijkamp (April 2003). "Immunoglobulin free light chains and mast cells: pivotal role in T-cell-mediated immune reactions?".
2376:
Jagannath S (September 2007). "Value of serum free light chain testing for the diagnosis and monitoring of monoclonal gammopathies in hematology".
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730:
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448:
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589:
Russo LM, Bakris GL, Comper WD, Bakris, Comper (May 2002). "Renal handling of albumin: a critical review of basic concepts and perspective".
150:). The passage of large amounts of immunoglobulin light chains through the kidneys may cause inflammation or blockage of the kidney tubules.
372:
Janeway CA, Travers P, Walport M, Slomchik MJ, "Immunobiology; the immune system in health and disease" (2005); Garland
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209:
of the bone. Abnormal free light chain production has also been reported to be prognostic of a worse outcome in multiple myeloma and
1843:"Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma"
559:
Miettinen, T, Kekki M (1967). "Effect of impaired hepatic and renal function on bence jones protein catabolism in human subjects".
2284:
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1731:"Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance"
2126:"International Myeloma Working Group guidelines for serum-free light-chain analysis in multiple myeloma and related disorders"
1569:"Serum free light chain (FLC) measurement can aid capillary zone electrophoresis in detecting subtle FLC-producing M proteins"
1430:"Quantitative analysis of serum free light chains: A new marker for the diagnostic evaluation of primary systemic amyloidosis"
1687:"Correlation of serum immunoglobulin free light chain quantification with urinary Bence Jones protein in light chain myeloma"
977:
295:
532:
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254:
Technical and clinical reviews of serum free light-chain measurement have recently been written by Pratt and
Jagannath.
384:
213:. An abnormal light-chain ratio has been defined as a kappa to lambda chain ratio of less than 0.26 or more than 1.65.
1514:"Serum free light chains: An alternative to the urine Bence Jones proteins screening test for monoclonal gammopathies"
377:
1566:
1567:
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1066:
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1003:
230:
210:
123:
pores that allow filtration of immunoglobulin light chains and other small molecules from the blood into the
73:. The sheets are linked by a disulfide bridge and together form a roughly barrel-shaped structure known as a
1289:"Nonsecretory plasma cell myeloma—becoming even more rare with serum free light-chain assay: A brief review"
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2008:
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1968:
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1414:
1033:
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2340:
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1892:"Immunoglobulin free light chains and solitary plasmacytoma of bone"
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162:
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Light chains are incorporated into immunoglobulin molecules during
2329:"The evolving use of serum free light chain assays in haematology"
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1179:
2030:
1840:
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959:
177:
The 500 mg of FLCs produced per day by the normal
2123:
2283:
229:
The serum free light-chain assay in combination with
1728:
2250:
157:
of the kidneys secrete large amounts of uromucoid (
2079:
1981:
1889:
1684:
199:monoclonal gammopathy of undetermined significance
1468:
558:
2422:
2206:
2258:. UKMF Guidelines Working Group. Archived from
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640:The American Journal of the Medical Sciences
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1122:
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1754:
1702:
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111:composed of approximately half a million
2182:
1319:
994:
552:
2326:
1286:
841:
674:
631:
584:
582:
14:
2423:
1573:American Journal of Clinical Pathology
1434:American Journal of Clinical Pathology
389:
264:
43:Measurement of the serum level of FLCs
917:The Journal of Clinical Investigation
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737:
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2369:
2320:
2277:
2244:
2200:
2176:
2117:
2073:
2024:
1975:
1932:
1883:
1834:
1771:
1678:
1642:
1615:
1560:
1505:
1462:
1421:
1377:
1280:
1222:
953:
904:
184:
2333:British Journal of Haematology
2210:American Journal of Hematology
2083:British Journal of Haematology
1941:British Journal of Haematology
1387:British Journal of Haematology
1072:American Journal of Hematology
525:
490:
455:
366:
13:
1:
1148:10.1158/1078-0432.CCR-05-0486
1018:10.1016/S0140-6736(03)12457-9
817:10.1016/S0002-9440(10)64142-9
476:10.1016/S1471-4906(03)00059-0
288:10.1016/S0076-6879(85)16008-8
257:
247:stringent complete response.
241:
231:serum protein electrophoresis
216:
211:chronic lymphocytic leukaemia
105:
96:
2049:10.1182/blood-2007-01-067728
1908:10.1182/blood-2006-04-015784
1859:10.1182/blood-2007-08-108357
1531:10.1373/clinchem.2006.069104
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1305:10.5858/2006-130-1212-NPCMEM
1198:10.1182/blood-2008-02-138602
573:10.1016/0009-8981(67)90036-8
546:10.1016/0009-8981(67)90036-8
224:
80:
64:
7:
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1447:10.1309/LYWM-47K2-L8XY-FFB3
10:
2447:
1796:10.1016/j.blre.2007.01.002
1747:10.1182/blood-2005-03-1038
115:. Each nephron contains a
1704:10.1093/clinchem/48.4.655
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511:10.3109/00365517609054462
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464:Trends in Immunology
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2417:at Lab Tests Online
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203:smouldering myeloma
148:Bence Jones protein
2194:10.53347/rid-73043
1691:Clinical Chemistry
1664:10.4065/81.12.1575
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343:10.1038/ki.2011.94
27:Aspect of medicine
2222:10.1002/ajh.20381
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970:10.1159/000096761
929:10.1172/JCI115629
866:10.1172/JCI114474
591:Am. J. Kidney Dis
417:10.1172/JCI107023
336:(12): 1289–1301.
297:978-0-12-182016-9
121:basement membrane
47:
46:
16:(Redirected from
2438:
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2401:
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2324:
2318:
2317:
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2265:on 13 April 2009
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127:of the nephron.
71:β-pleated sheets
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1850:
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1741:(3): 812–7.
1738:
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1623:
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1603:cite journal
1576:
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1548:cite journal
1521:
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1477:(4): 210–5.
1474:
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1390:
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1009:
1005:
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860:(2): 570–6.
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207:plasmacytoma
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185:Clinical use
176:
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2431:Blood tests
540:: 395-407.
195:Mayo Clinic
59:amyloidosis
2153:2318/70035
567:(3): 395.
258:References
242:Monitoring
233:and serum
217:Guidelines
117:glomerulus
106:Metabolism
97:Production
352:0085-2538
225:Diagnosis
81:Synthesis
65:Structure
2425:Category
2398:18021469
2363:40081613
2355:18318757
2314:14838196
2306:16855634
2286:Leukemia
2238:21769919
2230:16044444
2170:28720792
2162:19020545
2130:Leukemia
2111:28394748
2103:19016722
2067:17416735
2018:18596742
1988:Leukemia
1969:36047195
1961:17408464
1926:16741249
1877:17942755
1814:17367905
1765:15855274
1713:11901068
1672:17165636
1636:16682511
1595:16040291
1540:16858075
1491:16399645
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1026:12583950
988:17075224
835:11337384
668:26350666
611:11979334
484:12697449
360:21490587
201:(MGUS),
163:polymers
113:nephrons
75:β-barrel
2058:1924775
2009:2614406
1917:1895544
1868:2200851
1805:3904304
1756:1895159
1499:7839338
1471:Amyloid
1260:8779162
1207:2964259
1164:1290359
1102:1067413
947:1737851
884:2298921
826:1891942
717:4165739
708:2138312
660:4217565
435:5054468
306:3937021
140:cubulin
136:megalin
132:albumin
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2166:S2CID
2107:S2CID
2037:Blood
1965:S2CID
1896:Blood
1847:Blood
1735:Blood
1495:S2CID
1411:S2CID
1256:S2CID
1232:Blood
1186:Blood
1160:S2CID
1098:S2CID
1030:S2CID
664:S2CID
119:with
2394:PMID
2351:PMID
2302:PMID
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2226:PMID
2158:PMID
2099:PMID
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2014:PMID
1957:PMID
1922:PMID
1873:PMID
1828:link
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