Table of Contents

Locator Record

Title: Monoclonal gammopathy of undetermined significance (MGUS) (SSNH3OL )
Contact Number: 1-866-441-NCHS
Years of Content: 1988 - 1994
First Published: August, 2012
Revised: NA
Access Constraints: None
Use Constraints: None
Geographic Coverage: National
Subject:Monoclonal gammopathy of undetermined significance (MGUS)
Record Source: NHANES 1988 - 1994
Survey Methodology: NHANES 1988 - 1994 is a stratified multistage probability sample of the civilian non-institutionalized population of the U.S.
Medium: NHANES Web site; SAS transport files

Component Description

Conduct serum protein electrophoresis, immunofixation analyses, and kappa and lambda free light chain (FLC) assays in serum, to determine the age-adjusted prevalence and monoclonal protein size distribution of MGUS by ethnic/racial group. Using our results from applied serum analyses, in combination with available information from the NHANES surveys (such as data from medical exams; routine blood samples; questionnaires covering medical history, drug intake, nutrition, smoking, and demographics), we will be able to dissect etiologic mechanisms involved in MGUS development and transformation to full-blown multiple myeloma.

Because the mucosal immune system is a a major site of extrinsic immune stimuation, and celiac disease is associated with a potent stimulation of the gut immune system, elaborating both T cell and B cell mediated immune responses, typically associated with an increase in expansion of B cells and plasma cells within the gut the assays also include serologic testing for celiac disease. Immune responses in celiac disease include both IgA and IgG and possibly IgM responses. Celiac disease may affect as many as 1% of the population but most remain undiagnosed. Celiac disease has also occasionally been reported in association with multiple myeloma. Using the celiac assays we are evaluating if there is any correlation between seropositivity for celiac disease and markers for plasma protein abnormalities.

Eligible Sample

Participants ≥ 50 years of age from NHANES III and NHANES 1999-2004.

Description of Laboratory Methodology

Measurement of Serum Protein Markers

 A total of 250 microliter of serum was used for each study subject to perform the analyses to detect and quantify M protein and FLC (described below). For those individuals where an abnormal protein band or equivocal pattern with conventional agarose-gel electrophoresis was found, an additional 250 microliter serum was used to perform immunofixation for validation purposes (see below).

Electrophoresis

First, serum samples were analyzed for all identified subjects (described above) by using conventional agarose-gel electrophoresis, which has been described in detail previously. This revealed the occurrence and pattern (including determination of the size) of M proteins in the study cohort. If there was an abnormal band or equivocal pattern, immunofixation was performed to validate and to specify type of M protein.

Free light chains

FLC levels were determined in all positive study samples (described above) using the FLC assay (Freelite; The Binding Site, Birmingham, United Kingdom) performed on a Dade-Behring Nephelometer (Deerfield, IL). It consists of two separate measurements, one to detect free-kappa (normal range, 3.3-19.4 mg/L) and the other to detect free-lambda (normal range, 5.7-26.3 mg/L) light chains. In addition to measuring the absolute levels of FLC, the test also allows the assessment of clonality based on the ratio of kappa-lambda light chain levels (normal reference range, 0.26-1.65). Subjects with a kappa-lambda FLC ratio less than 0.26 are typically defined as having monoclonal lambda FLC and those with ratios greater than 1.65 are defined as having a monoclonal kappa FLC. If the FLC ratio is greater than 1.65, kappa is considered to be the “involved” FLC and lambda the “uninvolved” FLC, and vice versa if the ratio is less than 0.26. The normal reference range of 0.26 to 1.65 for the free-kappa-lambda ratio in the FLC assay reflects a higher serum level of free-lambda light chains than would be expected given the usual kappa-lambda ratio of two intact immuno¬globulins. This occurs because the renal excretion of free kappa (which exists usually in a monomeric state) is much faster than free lambda (which is usually in a dimeric state).

Celiac assays

Testing consists of a sequential test strategy, which has proven both sensitive and specific for establishing a serologic diagnosis of celiac disease. The first level test consists of a tissue transglutaminase IgA ELISA test and, for patients who’s test exceeds the normal range, a confirmatory test with endomysial antibody by immunofluorescence is then carried out.

Description of Laboratory Methodology

All protein analyses in this study will be performed at the Protein Immunology Laboratory at Mayo Clinic, Rochester, Minnesota. The Protein Immunology Laboratory is the leading laboratory in the world with regard to protein studies on MGUS and multiple myeloma. Since the early 1960’s Mayo Clinic have published extensively in this field. In order to assess accuracy and precision before study start, we performed quality control (QC) analyses of serum from 2 positive MGUS subjects (known to have MGUS), 2 negative MGUS subject (known not to have MGUS), 2 positive FLC subjects (known to have FLC), and 2 negative FLC subject (known not to have FLC). Briefly, for each of these six QC individuals, we aliquoted serum into 5 tubes at an NCI laboratory and thereafter sent the serum in blinded tubes to the Protein Immunology Laboratory at Mayo Clinic for analyses of M protein and FLC, respectively. The results were very stable.

In terms of sample storage and potential influence on results; the Mayo Clinic lab has analyzed over 1,100 sera collected up to 35 years before testing, without any problems to perform the assays. The practice in the laboratory is to repeat the assay following a variety of storage activities. For example, serum is stored at room temperature for one week and the assays are repeated on days 1, 3, 5, and 7. Also, samples are refrigerated at 0 to 4 degrees Celsius for 7 days and then assays are repeated on days 1, 3, 5, and 7. Further, they freeze serum sample at -20 degrees Celsius for 1 and 2 weeks, then they thaw and run the assays. In addition, they subject samples to 3 cycles of freeze/thaw and then repeat the assays (personal communication, Dr. Kyle, December 2006). Thus, freeze/thaw steps will not have an adverse impact on the methods being used in our proposed study.

Data Processing and Editing

Data was received after all the laboratory testing was complete. The data were not edited.

Data Access: All data are publicly available.

References

Codebook and Frequencies

SEQN - Respondent sequence number

Variable Name:
SEQN
SAS Label:
Respondent sequence number
English Text:
Respondent sequence number.
Target:
Both males and females 1 YEARS - 150 YEARS

SSIMP - PEL_Impression

Variable Name:
SSIMP
SAS Label:
PEL_Impression
English Text:
PEL_Impression
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
PEL_Impression Value was recorded 6573 6573
< blank > Missing 1 6574

SSRES - IF_Result

Variable Name:
SSRES
SAS Label:
IF_Result
English Text:
IF_Result
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
IF_Result Value was recorded 508 508
< blank > Missing 6066 6574

SSSPIKE - Size of peak if available

Variable Name:
SSSPIKE
SAS Label:
Size of peak if available
English Text:
Size of peak if available
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0 to 3.2 Range of Values 320 320
. Missing 6254 6574

SSSPIKE2 - Size of 2nd peak if available

Variable Name:
SSSPIKE2
SAS Label:
Size of 2nd peak if available
English Text:
Size of 2nd peak if available
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0.5 0.5 1 1
1.2 1.2 1 2
< blank > Missing 6572 6574

SSTOTAL - Total_Protein

Variable Name:
SSTOTAL
SAS Label:
Total_Protein
English Text:
Total_Protein
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
2.6 to 17.1 Range of Values 503 503
. Missing 6071 6574

SSALB - Albumin

Variable Name:
SSALB
SAS Label:
Albumin
English Text:
Albumin
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1.5 to 6.8 Range of Values 503 503
. Missing 6071 6574

SSA1 - Alpha1

Variable Name:
SSA1
SAS Label:
Alpha1
English Text:
Alpha1
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0.1 to 0.8 Range of Values 503 503
. Missing 6071 6574

SSA2 - Alpha2

Variable Name:
SSA2
SAS Label:
Alpha2
English Text:
Alpha2
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0.3 to 2.1 Range of Values 503 503
. Missing 6071 6574

SSBETA - Beta

Variable Name:
SSBETA
SAS Label:
Beta
English Text:
Beta
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0.4 to 3.6 Range of Values 503 503
. Missing 6071 6574

SSGAM - Gamma

Variable Name:
SSGAM
SAS Label:
Gamma
English Text:
Gamma
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0.3 to 4.2 Range of Values 503 503
. Missing 6071 6574

SSAG_R - Albumin/Gamma

Variable Name:
SSAG_R
SAS Label:
Albumin/Gamma
English Text:
Albumin/Gamma
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0.52 to 5.83 Range of Values 503 503
. Missing 6071 6574

SSK_FLC - Kappa FLC

Variable Name:
SSK_FLC
SAS Label:
Kappa FLC
English Text:
Kappa FLC
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0.149 to 285 Range of Values 483 483
. Missing 6091 6574

SSL_FLC - Lambda FLC

Variable Name:
SSL_FLC
SAS Label:
Lambda FLC
English Text:
Lambda FLC
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0.362 to 67.5 Range of Values 483 483
. Missing 6091 6574

SSKL_R - K/L Ratio

Variable Name:
SSKL_R
SAS Label:
K/L Ratio
English Text:
K/L Ratio
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0.0051 to 47.9 Range of Values 483 483
. Missing 6091 6574

SSK_FLCX - Denotes imprecise kappa (n=2)

Variable Name:
SSK_FLCX
SAS Label:
Denotes imprecise kappa (n=2)
English Text:
Denotes imprecise kappa (n=2)
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
< blank > Missing 6574 6574

SSKL_RX - Denotes imprecise k/l (n=2)

Variable Name:
SSKL_RX
SAS Label:
Denotes imprecise k/l (n=2)
English Text:
Denotes imprecise k/l (n=2)
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
< blank > Missing 6574 6574

SSIS - Flag:Insufficient sample

Variable Name:
SSIS
SAS Label:
Flag:Insufficient sample
English Text:
Flag:Insufficient sample
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 1 78 78
< blank > Missing 6496 6574

SSTTGV - TTG IGA value

Variable Name:
SSTTGV
SAS Label:
TTG IGA value
English Text:
TTG IGA value
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
0.26 to 332.2 Range of Values 6051 6051
. Missing 523 6574

SSTTGR - TTG IGA result

Variable Name:
SSTTGR
SAS Label:
TTG IGA result
English Text:
TTG IGA result
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
NEG NEG 5966 5966
POS POS 11 5977
WKPOS WKPOS 74 6051
< blank > Missing 523 6574

SSEMA - EMA result

Variable Name:
SSEMA
SAS Label:
EMA result
English Text:
EMA result
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
NA NA 5963 5963
NEG NEG 81 6044
POS POS 7 6051
< blank > Missing 523 6574

SSSERO - Serology result (associated with CD)

Variable Name:
SSSERO
SAS Label:
Serology result (associated with CD)
English Text:
Serology result (associated with CD)
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
IND IND 78 78
NEG NEG 5966 6044
POS POS 7 6051
< blank > Missing 523 6574

SSOL_H - Heavy chain MGUS

Variable Name:
SSOL_H
SAS Label:
Heavy chain MGUS
English Text:
Heavy chain MGUS
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
A IgA 15 15
BI Biclonal 14 29
G IgG 146 175
M IgM 25 200
< blank > Missing 6374 6574

SSOL_L - Light chain MGUS

Variable Name:
SSOL_L
SAS Label:
Light chain MGUS
English Text:
Light chain MGUS
Target:
Both males and females 1 YEARS - 150 YEARS
Code or Value Value Description Count Cumulative Skip to Item
BI Biclonal 14 14
K Kappa 116 130
L Lambda 70 200
< blank > Missing 6374 6574