Cellular and Molecular Medicine Research, ISSN 2817-6359 online, Open Access
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Original Article

Volume 3, Number 1, August 2025, pages 1-12


Screening for Light Chain Monoclonal Gammopathy of Undetermined Significance: Pseudo Epidemic Based on Current Diagnostic Criteria

Tables

↓  Table 1. Categorization of Urine Immunofixation Analysis
 
UIFE Age in years Race Gender
Range Average SD White Black Hispanic Other Female Male
UIFE-0 specimens were from patients without any indication of monoclonal gammopathy, except isolated presence of monoclonal light chain in urine. UIFE-1 specimens were from patients with extant monoclonal gammopathy or history of monoclonal gammopathy. UIFE-3 specimens were from patients with ambiguous results and UIFE-4 specimens were from one patient with polymorphus sarcoma. The number of specimens for which κ/λ ratio results were available are given in parentheses. UIFE: urine protein immunofixation electrophoresis.
UIFE-0 (with κ/λ ratio) 3,230 (1,740) 18 - 96 61.2 14.6 1,556 1,505 46 123 1,795 1,435
UIFE-1 (with κ/λ ratio) 1,723 (1,589) 27 - 97 65.3 11.3 695 972 18 38 780 943
UIFE-3 42
UIFE-4 3
Total UIFE 4,998

 

↓  Table 2. Numbers and Percentage of Specimens in the UIFE-0 Category With Available SFLC Levels (N = 1,740) With Monoclonal Light Chains in Groups With Various Ranges of κ/λ Ratios
 
Kappa, N Kappa, % Lambda, N Lambda, %
More than 80% of the specimens with associated serum κ/λ ratio of > 3.0 or 3.15 did not exhibit monoclonal light chains in urine, or any other evidence of a monoclonal lesion. aUIFE Neg for kappa specimen with κ/λ ratio 11.53, patient with cirrhosis and creatinine 2.17. bFurther breakdown and data on these seven specimens are presented below in Table 3. cAdditional data for this group are shown in Table 4. FMLC: free monoclonal light chain; MG: monoclonal gammopathy; SFLC: serum free light chain; UIFE: urine protein immunofixation electrophoresis; UIFE-0: specimens from patients without evidence or history of MG, except solitary finding of FMLC in urine.
Total UIFE-0 with κ/λ ratio 1,740
κ/λ ratio of ≤ 0.25 7b 0 0 3 42.9
κ/λ ratio of 0.26 to ≤ 1.65 1,133 8 0.7 13 1.1
κ/λ ratio of 1.66 to 2.99 547 13 2.4 1 0.2
κ/λ ratio of 3 to 353c 53 10 18.8 0 0
κ/λ ratio of 3 to 10 46 4 8.7 0 0
κ/λ ratio of 10 to 353 7a 6 85.7 0 0
κ/λ ratio 0.26 - 0.75 45 0 0 12 26.7

 

↓  Table 3. Additional Laboratory Data for the Seven Instructive Specimens With κ/λ Ratio of ≤ 0.25
 
UIFE-0 with κ/λ ratio ≤ 0.25
UIFE κ/λ ratio Gamma globulin, g/dL Urine protein, mg/dL
aSpecimens from same patient. One of the three urines without monoclonal lambda light chains was from a patient who had two urine specimens with monoclonal lambda light chain in urine; the serum specimens corresponding to the lambda monoclonal positive urine specimens had lower κ/λ ratios of 0.14 and 0.19 and higher urine protein levels, while the negative urine specimen was associated with a κ/λ ratio of 0.22 and lower total urine protein of ≤ 4.0 mg/dL. The negative result on UIFE for this patient was likely due to a combination low levels of free monoclonal lambda chains and a dilute urine that may not have been concentrated optimally. bThis specimen with κ/λ ratio of 0.22 and urine negative for monoclonal light chains was from a 21-year-old patient with acute myeloid leukemia treated with stem cell transplantation. FMLC: free monoclonal light chain; MG: monoclonal gammopathy; UIFE: urine protein immunofixation electrophoresis; UIFE-0: specimens from patients without evidence or history of MG, except solitary finding of FMLC in urine.
Negative 0.11 3.54 33
Negative 0.12 2.24 1,221
Lambdaa 0.14 0.81 11
Lambdaa 0.19 0.89 5
Lambda 0.21 1.9 19
Negativea 0.22 1.02 ≤ 4
Negativeb 0.22 0.49 26

 

↓  Table 4. Data From Patients With κ/λ Ratio 3 to 353 Regarding Average Total Urine Protein, dK, Gamma Globulins and eGFR to Contrast the Findings in Specimens Positive for Kappa Monoclonal Light Chains and Those Negative by UIFE
 
UIFE-0 with κ/λ ratio 3 to 353
Kappa UFLC Negative UFLC P value
Specimens with monoclonal Kappa in urine had higher dK, lower gamma globulins, and higher eGFR. The higher total protein in negative specimens may have interfered with concentration of urine. eGFR: estimated glomerular filtration rate; FMLC: free monoclonal light chain; MG: monoclonal gammopathy; UIFE: urine protein immunofixation electrophoresis; UIFE-0: specimens from patients without evidence or history of MG, except solitary finding of FMLC in urine.
Average total protein 74 173 < 0.23
Average dK 30.73 12.18 < 0.0092
Average γ globulin 0.92 1.82 < 0.01
eGFR 65.67 43.65 < 0.023

 

↓  Table 5. The Range of Total Urine Protein and the Number and Percentage of Specimens With Monoclonal Light Chains, Kappa or Lambda, in the UIFE-0 Group
 
UIFE in UIFE-0 and total urine protein, mg/dL
Urine protein, mg/dL Number UIFE positive, N UIFE positive, %
UIFE: urine protein immunofixation electrophoresis; UIFE-0: specimens from patients without evidence or history of MG, except solitary finding of FMLC in urine.
≤ 4 270 0 0.0
5 - 10 972 11 1.1
11 - 15 377 5 1.3
16 - 20 213 6 2.8
21 - 25 156 6 3.8
26 - 30 126 3 2.4
31 - 7,408 1,108 37 3.19
Total 3,222 68 2.11

 

↓  Table 6. UIFE Data for Specimens From Patients With or History of Monoclonal Gammopathy
 
UIFE-1 total 1,723 (light chain type unresolved = 49)b
Kappa, N Kappa, % Lambda, N Lambda, %
The number and percentage of specimens exhibiting monoclonal light chains in urine. a*Upper observed limits of κ/λ ratio for kappa and lambda chain lesions, respectively. bDespite a history of prior monoclonal gammopathy, the light chain type could not be ascertained from the records as many patients were referred to this institution for consideration of autologous bone marrow transplantation and the referral materials did not include the isotype of the involved immunoglobulin and one was not ascertained at this institution. cUIFE results did not display an unambiguous monoclonal light chain band, had a biclonal or oligoclonal pattern, or displayed heavy chain only. UIFE: urine protein immunofixation electrophoresis; UIFE-1 specimens were from patients with extant monoclonal gammopathy or history of monoclonal gammopathy.
Total UIFE-1 with κ/λ ratio 1,589
κ/λ ratio of < 0.25 222 0 0.0 186 83.8
κ/λ ratio of 0.26 to ≤ 1.65 532 47 8.8 108 20.3
κ/λ ratio of 1.66 to 3.0 257 65 25.3 9 3.5
κ/λ ratio of 3 to 8,285a/317a 478 393 82.2 0 0
Unresolvedc 25 26

 

↓  Table 7. Subtypes of Specimens From Patient With Lambda Chain Associated Monoclonal Gammopathy or History of Such Lesion
 
UIFE-1 lambda Number
SFLC: serum free light chain; UIFE: urine protein immunofixation electrophoresis; UIFE-1 specimens were from patients with extant monoclonal gammopathy or history of monoclonal gammopathy.
Total specimens 658
Specimens with SFLC data 599
Lambda UIFE positive total 329
Lambda UIFE positive with SFLC 302
Neg UIFE for lambda 292
UIFE positive for kappa 5
Unresolved 27

 

↓  Table 8. Numbers and percentages of UIFE-1 Lambda Specimens Displaying Monoclonal Light Chains at Various κ/λ Ratio Categories
 
UIFE-1 lambda UIFE positive by κ/λ ratio, number and percentage
κ/λ ratio Total in category Number positive Percentage positive
UIFE: urine protein immunofixation electrophoresis; UIFE-1 specimens were from patients with extant monoclonal gammopathy or history of monoclonal gammopathy.
κ/λ ratio ≤ 0.25 230 185 30.9
κ/λ ratio 0.26 to ≤ 0.75 120 64 10.7
κ/λ ratio 0.75 to ≤ 1.65 195 44 7.3
κ/λ ratio 1.66 to 3.1 54 9 1.5

 

↓  Table 9. Numbers and Percentages of UIFE-1 Lambda Specimens Displaying Monoclonal Light Chains in Various dL Categories
 
UIFE-1 lambda by net lambda (dL)
dL range Number in category Number positive % positive
Lowest dL = -8.1 with positive UIFE; lambda total level 11.65; κ/λ ratio 1.7. Lowest observed dL = -20.34, UIFE was neg; highest dL with Neg UIFE = 324.33. Lowest lambda total with pos UIFE = 0.24 Urine IgG L. UIFE: urine protein immunofixation electrophoresis; UIFE-1 specimens were from patients with extant monoclonal gammopathy or history of monoclonal gammopathy.
dL ≤ 1 273 64 10.7
dL 1 - 2 30 16 2.7
dL 2 - 3 26 11 1.8
dL ≥ 3.0 270 214 35.7
dL 3 - 10 78 53 8.8

 

↓  Table 10. Numbers and Percentages of UIFE-1 Lambda Specimens Displaying Monoclonal Light Chains in Various Categories by Total Urine Protein Levels
 
UIFE-1 lambda and total urine protein, mg/dL
Urine protein, mg/dL Number in category Number positive % positive
The kappa marked with * was IgG kappa. Other kappas were monoclonal kappa light chain bands. UIFE: urine protein immunofixation electrophoresis; UIFE-1 specimens were from patients with extant monoclonal gammopathy or history of monoclonal gammopathy.
≤ 4.0 54 5 9.3
5 to 10 171 41 + 1K* 24.0
11 to 15 52 30 + 3K 57.7
16 to 20 42 23 54.8
21 to 25 42 22 + 1K 59.1
26 to 30 22 13 59.1
31 to 5,445 267 192 71.9

 

↓  Table 11. Subtypes of Specimens From Patient With Kappa Chain Associated Monoclonal Gammopathy or History of Such Lesion, i.e., UIFE-1 Kappa
 
UIFE-1 kappa Number
SFLC: serum free light chain; UIFE-1 specimens were from patients with extant monoclonal gammopathy or history of monoclonal gammopathy.
Total specimens 1,024
Specimens with SFLC data 946
Kappa UIFE positive total 544
Kappa UIFE positive with SFLC 502
Neg UIFE for kappa 450
UIFE positive for lambda 0
Unresolved 30

 

↓  Table 12. Numbers and Percentages of UIFE-1 Kappa Specimens Displaying Monoclonal Light Chains at Various κ/λ Ratio Categories
 
UIFE-1 kappa UIFE positive by κ/λ ratio, % from total of 946
κ/λ ratio Number in category Number positive Percentage positive
aPositive for both Kappa and Lambda monoclonal light chains with kappa being the dominant band. UIFE-1 specimens were from patients with extant monoclonal gammopathy or history of monoclonal gammopathy.
κ/λ ratio ≤ 0.25 1 1a 100.0
κ/λ ratio ≤ 0.75 19 1 5.3
κ/λ ratio ≤ 1.65 222 45 19.4
κ/λ ratio 1.66 to 2.99 162 104 63.6
κ/λ ratio 3 - 10 214 63 29.9
κ/λ ratio 10 - 8,285 328 290 88.4
κ/λ ratio 3 - 8,285 542 353 65.1

 

↓  Table 13. Numbers and Percentages of UIFE-1 Kappa Specimens Displaying Monoclonal Light Chains in Various dK Categories
 
UIFE-1 kappa by net kappa (dK)
dK range Number in category Number positive % positive
Lowest dK = -44.72 with positive UIFE; kappa total level 6.46; κ/λ ratio 0.13. Lowest observed dK = -44.72, UIFE was positive for both kappa and lambda. Highest dK with Neg UIFE = 317.3. Lowest kappa total with pos UIFE = 0.23 Urine IgG kappa. UIFE-1 specimens were from patients with extant monoclonal gammopathy or history of monoclonal gammopathy.
dK ≤ 1 296 61 20.6
dK 1 - 2 103 28 27.2
dK 2 - 3 66 29 43.9
dK 3.0 - 6,280 483 384 79.5
dK 3 - 10 162 92 56.8

 

↓  Table 14. Numbers and Percentages of UIFE-1 Kappa Specimens Displaying Monoclonal Light Chains in Various Categories by Total Urine Protein Levels
 
UIFE-1 kappa; total urine protein, mg/dL, N = 1,024
Urine protein, mg/dL Number in category Number positive % positive
UIFE-1 specimens were from patients with extant monoclonal gammopathy or history of monoclonal gammopathy.
≤ 4 94 7 7.4
5 to 10 259 69 26.6
11 to 15 114 47 41.2
16 to 20 87 56 64.4
20 to 25 56 40 71.4
26 to 30 40 28 70.0
31 to 4,880 374 297 79.4

 

↓  Table 15. Regression Report for UIFE-0
 
Estimate Std. error z value U Pr. (> |z|)
(Intercept) -4.678425 0.279579 -16.734 < 2 × 10-16***
U Pr. -0.006437 0.00261 -2.466 0.0137*
Lambda 0.088108 0.021271 4.142 3.44 × 10-5***
Ratio 0.52679 0.097425 5.407 6.40 × 10-8***
Number of positive and negative predictions (prediction accuracy rate is 0.977) Prediction_Neg Prediction_Pos
To improve the diagnosis accuracy, we fitted a multivariable logistic regression that includes urine protein (U Pr.), lambda and kappa/lambda ratio as independent variables. *P < 0.05; ***P < 0.001. UIFE-0: specimens from patients without evidence or history of MG, except solitary finding of FMLC in urine.
UIFE_Neg 1,693 0
UIFE_Pos 40 6