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We measured immunosuppression at myeloma diagnosis and assessed the impact on survival in 5826 UK myeloma trial patients. Polyclonal immunoglobulin levels were below normal in 85% of patients and above normal in only 0.4% of cases for IgA, 0.2% for IgM and no cases for IgG. Immunoparesis had a greater impact in recent trials: median overall survival (OS) was up to 3 years longer for patients without immunoparesis compared to the old trials, less than 1 year longer. Median progression-free survival (PFS) was 39%, 36% and 57% longer for patients with normal IgG, IgA and IgM levels, respectively. The depth of IgM suppression, but not the depth of IgG or IgA suppression, was prognostic for survival: the most severely suppressed IgM tertile of patients OS was 0.9 years shorter than those in the top tertile, and 2.6 years shorter than OS of those with normal IgM levels (p = .007). The degree of suppression of polyclonal IgM levels below normal was associated with worse PFS (p = .0002). Infection does not appear to be the main mechanism through which immunoparesis affects survival. We hypothesise that IgM immunoparesis impacts through a combination of being associated with more aggressive disease and reduced immune surveillance against relapse.

Background: Immunoglobulins (Ig) are essential for combating infectious disease. However, high levels are associated with a range of diseases and/or poor health behaviours, such as autoimmune diseases, chronic infection, HIV and excessive alcohol consumption. In the present analyses, we extend this body of work by examining whether higher levels of serum Ig G, A and M are associated with increased mortality risk., Methods: Participants were 4255 Vietnam-era, former US army personnel (the Vietnam Experience Study). From military service files, telephone interviews in 1983 and a medical examination in 1986, sociodemographic, and health data were collected. Contemporary morning fasted blood samples were taken from which IgG, IgA and IgM concentrations were determined. Mortality surveillance over 15 years gave rise to deaths ascribed to all-causes, cardiovascular disease mortality, all cancers combined mortality, external cause and 'other' causes (predominantly comprising deaths due to infectious disease). Cox proportional hazard models were utilised to compute HRs per SD increase in Ig which were first adjusted for age and then additionally adjusting for a range of candidate confounders., Results: In multiply adjusted analyses, in general, the higher the immunoglobulin concentration, the greater the risk of death. Thus, IgA (HR=2.0 95% CI 1.47 to 2.73), IgM (HR=1.5 95% CI 1.11 to 1.91) and IgG (HR=5.8 95% CI 3.38 to 9.95) were positively related to all-cause mortality. Corresponding results for 'other' causes of mortality were 4.7 (2.64 to 8.19), 3.5 (2.29 to 5.45) and 33.4 (15.13 to 73.64)., Conclusions: In the present study, high levels of Ig are associated with an elevated risk of death from total and 'other' causes, mainly infectious disease. High levels of Ig, particularly IgG, may signal subclinical disease., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Antibodies specific for the spike glycoprotein (S) and nucleocapsid (N) SARS-CoV-2 proteins are typically present during severe COVID-19, and induced to S after vaccination. The binding of viral antigens by antibody can initiate the classical complement pathway. Since complement could play pathological or protective roles at distinct times during SARS-CoV-2 infection we determined levels of antibody-dependent complement activation along the complement cascade. Here, we used an ELISA assay to assess complement protein binding (C1q) and the deposition of C4b, C3b, and C5b to S and N antigens in the presence of antibodies to SARS-CoV-2 from different test groups: non-infected, single and double vaccinees, non-hospitalised convalescent (NHC) COVID-19 patients and convalescent hospitalised (ITU-CONV) COVID-19 patients. C1q binding correlates strongly with antibody responses, especially IgG1 levels. However, detection of downstream complement components, C4b, C3b and C5b shows some variability associated with the subject group from whom the sera were obtained. In the ITU-CONV, detection of C3b-C5b to S was observed consistently, but this was not the case in the NHC group. This is in contrast to responses to N, where median levels of complement deposition did not differ between the NHC and ITU-CONV groups. Moreover, for S but not N, downstream complement components were only detected in sera with higher IgG1 levels. Therefore, the classical pathway is activated by antibodies to multiple SARS-CoV-2 antigens, but the downstream effects of this activation may differ depending the disease status of the subject and on the specific antigen targeted. [ABSTRACT FROM AUTHOR]

Objectives: Myeloma is characterised by the presence of monoclonal immunoglobulin (M‐protein) and the free light chain (FLC) in blood. We investigated whether these M‐proteins and FLC are detectable in myeloma patients' saliva to evaluate its utility for non‐invasive screening and monitoring of haematological malignancies. Methods: A total of 57 patients with monoclonal gammopathy and 26 age‐matched healthy participants provided paired serum and saliva samples for immunoglobulin characterisation and quantification. Results: Myeloma patients had IgG or IgA M‐protein levels ranging up to five times and FLC levels up to a thousand times normal levels of polyclonal immunoglobulins. Despite these highly elevated levels, only two IgG and no IgA M‐proteins or FLC could be detected in paired saliva samples. Most patients had reduced levels of serum polyclonal immunoglobulins, but all had normal levels of salivary IgA. Conclusions: Immunoglobulin transfer from blood is not determined by levels in the systemic circulation and more likely dictated by periodontal inflammation and the integrity of the oral epithelium. Immunoglobulins secreted by bone marrow plasma cells do not substantially enter saliva, which represents a poor medium for myeloma diagnosis. These findings, along with normal salivary IgA levels despite systemic immunoparesis, support a strong partitioning of oral from systemic humoral immunity. [ABSTRACT FROM AUTHOR]

Background: Myeloma is consistently preceded by premalignant monoclonal gammopathy of undetermined significance (MGUS). In >5% of MGUS patients there is a second MGUS clone (biclonal gammopathy of undetermined significance; BGUS), yet, at myeloma diagnosis, presentation of biclonal gammopathy myeloma (BGMy) is considered less frequent, implying that myeloma eradicates coexisting MGUS.Methods: In the largest study of its kind, we assessed BGMy frequency amongst 6399 newly diagnosed myeloma patients enrolled in recent UK clinical trials.Results: Compared to expected prevalence (i.e., >5% of MGUS have BGUS), only 58 of 6399 (0.91%) newly diagnosed myeloma patients had BGMy, indicating myeloma typically eliminates coexistent MGUS. In these 58 BGMy cases, the MGUS plasma cell clone was greatly suppressed in size compared to typical levels observed in conventional MGUS; contrarily, the MGUS clone did not inhibit the myeloma plasma cell clone in BGMy.Conclusion: Myeloma eliminates the majority of competing MGUS, and when it does not, the MGUS clone is substantially reduced in size. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common in patients with multiple myeloma (MM). Whether serum free light chain (sFLC) measurements can distinguish between myeloma and other causes of AKI requires confirmation to guide early treatment. A rapid and portable sFLC test (Seralite®) is newly available and could reduce delays in obtaining sFLC results and accelerate diagnosis in patients with unexplained AKI. This study evaluated the accuracy of Seralite® to identify MM as the cause of AKI.Method: sFLCs were retrospectively analysed in patients with AKI stage 3 as per KDIGO criteria (i.e. serum creatinine ≥354 μmol/L or those on dialysis treatment) (n = 99); 45/99 patients had a confirmed MM diagnosis.Results: The Seralite® κ:λ FLC ratio accurately diagnosed all MM patients in the presence of AKI: a range of 0.14-2.02 returned 100% sensitivity and specificity for identifying all non-myeloma related AKI patients. The sFLC difference (dFLC) also demonstrated high sensitivity (91%) and specificity (100%): an optimal cut-off of 399 mg/L distinguished between myeloma and non-myeloma AKI patients. We propose a pathway of patient screening and stratification in unexplained AKI for use of Seralite® in clinical practice, with a κ:λ ratio range of 0.14-2.02 and dFLC 400 mg/L as decision points.Conclusions: Seralite® accurately differentiates between AKI due to MM and AKI due to other causes in patients considered at risk of myeloma. This rapid test can sensitively screen for MM in patients with AKI and help inform early treatment intervention. [ABSTRACT FROM AUTHOR]

Background: Serum free light chains (FLC) are sensitive biomarkers used for the diagnosis and management of plasma cell dyscrasias, such as multiple myeloma (MM), and are central to clinical screening algorithms and therapy response criteria. We have developed a portable, near-patient, lateral-flow test (Seralite®) that quantitates serum FLC in 10 min, and is designed to eliminate sample processing delays and accelerate decision-making in the clinic. Methods: Assay interference, imprecision, lot-to-lot variability, linearity, and the utility of a competitive-inhibition design for the elimination of antigen-excess ('hook effect') were assessed. Reference ranges were calculated from 91 healthy donor sera. Preliminary clinical validation was conducted by retrospective analysis of sera from 329 patients. Quantitative and diagnostic results were compared to Freelite®. Results: Seralite® gave a broad competitive-inhibition calibration curve from below 2.5 mg/L to above 200 mg/L, provided good assay linearity (between 1.6 and 208.7 mg/L for κ FLC and between 3.5 and 249.7 mg/L for λ FLC) and sensitivity (1.4 mg/L for κ FLC and 1.7 mg/L for λ FLC), and eliminated anomalous results from antigen-excess. Seralite® gave good diagnostic concordance with Freelite® (Roche Hitachi Cobas C501) identifying an abnormal FLC ratio and FLC difference in 209 patients with newly diagnosed MM and differentiating these patients from normal healthy donors with polyclonal FLC. Conclusions: Seralite® sensitively quantitates FLC and rapidly identifies clinical conditions where FLC are abnormal, including MM. [ABSTRACT FROM AUTHOR]

Background: Free light chains (FLCs) have a range of biological functions and may act as a broad marker of immune suppression and activation and inflammation. Measurement of salivary FLCs may provide practical advantages in a range of clinical populations. The aim of the present study was to develop normal reference ranges of FLCs in saliva and assess the effects of acute exercise on FLC levels in younger and older adults. Methods: Saliva FLC concentrations and secretion rates were measured in young (n = 88, aged 18-36) and older (n = 53, aged 60-80) adults. To assess FLC changes in response to acute exercise, young adults completed a constant work-rate cycling exercise trial at 60% VO2max (n = 18) or a 1 h cycling time trial (TT) (n = 10) and older adults completed an incremental submaximal treadmill walking exercise test to 75% HRmax (n = 53). Serum FLCs were measured at baseline and in response to exercise. Results: Older adults demonstrated significantly higher levels of salivary FLC parameters compared with young adults. Median (5-95th percentile) concentrations were 0.45 (0.004-3.45) mg/L for kappa and 0.30 (0.08-1.54) mg/L for lambda in young adults; 3.91 (0.75-19.65) mg/L for kappa and 1.00 (0.02-4.50) mg/L for lambda in older adults. Overall median concentrations of salivary kappa and lambda FLCs were 10-fold and 20-fold lower than serum, respectively. Reductions in salivary FLC concentrations and secretion rates were observed immediately post- and at 1 h post exercise, but were only significant for the older cohort; FLCs began to recover between post and 1 h post-exercise. No changes in serum FLCs were observed in response to exercise. Conclusions: The ability to assess FLCs in saliva and the reference ranges provided will likely broaden the use of this biomarker in healthy and clinical populations. The elevated salivary FLCs in older adults may relate to a deterioration of oral health and be important in the context of inflammatory processes and diseases associated with ageing. Exercise did not affect serum FLCs, but reduced salivary FLCs, most notably in older adults, which may reflect reduced transport of FLCs from serum into saliva. [ABSTRACT FROM AUTHOR]

Background: Bacterial infections in the elderly are common and associated with high morbidity and mortality, with pneumonia the second commonest cause of death. Reductions in antibodies against specific bacterial antigens in saliva and serum could contribute to infection risk in older adults, although they have yet to be examined in relation to age.Method: IgG, IgA and IgM antibody levels in paired saliva and serum samples were measured against 12 pneumococcal, 4 meningococcal and haemophilus polysaccharide antigens and diphtheria and tetanus toxoids in healthy younger (n = 28, 21-34 years) and older (n = 44, 60-80 years) adults.Results: Older adults had lower antibody concentrations in saliva than young adults, with the most striking differences observed for salivary antibody secretion rates. In serum, older adults registered lower concentrations for only a minority of antibodies. Young adults who had previously received a polysaccharide pneumococcal vaccination (PPV23) had higher levels of anti-pneumococcal antibodies in serum and in saliva. Only minor differences were observed in antibody levels between older adults who had/had not received PPV23, and there was no evidence of memory in saliva.Conclusions: Age differences were much greater in salivary antibodies than in serum; older adults had reduced salivary secretion rates of antibodies across bacterial antigens. This decline in local immunity may contribute to increased infection risk in the elderly. The poor memory from pneumococcal vaccination in serum and saliva suggests that PPV23 may be ineffective in older adults for both systemic and local protection. [ABSTRACT FROM AUTHOR]

Bacteremia caused by nontyphoidal strains of Salmonella is endemic among African children. Case-fatality rates are high and antibiotic resistance increasing, but no vaccine is currently available. T cells are important for clearance of Salmonella infection within macrophages, but in Africa, invasive Salmonella disease usually manifests in the blood and affects children between 4 months and 2 y of age, when anti-Salmonella antibody is absent. We have previously found a role for complement-fixing bactericidal antibody in protecting these children. Here we show that opsonic activity of antibody and complement is required for oxidative burst and killing of Salmonella by blood cells in Africans. Induction of neutrophil oxidative burst correlated with anti-Salmonella lgG and 1gM titers and C3 deposition on bacteria and was significantly lower in African children younger than 2 y compared with older children. Preopsonizing Salmonella with immune serum overcame this deficit, indicating a requirement for antibody and/or complement. Using different opsonization procedures, both antibody and complement were found to be necessary for optimal oxidative burst, phagocytosis and killing of nontyphoidal Salmonella by peripheral blood cells in Africans. Although most strains of African nontyphoidal Salmonella can be killed with antibody and complement alone, phagocytes in the presence of specific antibody and complement can kill strains resistant to killing by immune serum. These findings increase the likelihood that an antibody-inducing vaccine will protect against invasive nontyphoidal Salmonella disease in African children. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor focusing on serum free light chains for monitoring multiple myeloma.

In 728 Swedish cases of monoclonal gammopathy of undetermined significance (MGUS), followed up to 30 years (median, 10 years), we estimated the cumulative risk of hematologic disorders originating from lymphoid and myeloid lineages. Using Cox regression models, we examined associations of demographic and laboratory factors with progression and determined the discriminatory power of 3 prediction models for progression. Eighty-four MGUS cases developed a lymphoid disorder, representing a cumulative risk of 15.4%. Multiple myeloma (MM) occurred in 53 patients, and the 30-year cumulative risk was 10.6%; an ∼0.5% annual risk. Three factors were significantly associated with progression: abnormal free light-chain (FLC) ratio (<0.26 or >1.65), M-protein concentration (⩾1.5 g/dL), and reduction of 1 or 2 noninvolved immunoglobulin isotype levels (immunoparesis). A prediction model with separate effects for these 3 factors and the M-protein isotype had higher discriminatory power than other models, although the differences were not statistically significant. The 30-year cumulative risk for myeloid malignancies was <2%. Our study confirms that abnormal FLC ratio and M-protein concentration >1.5 g/dL, factors previously considered by Mayo Clinic researchers, are predictors for MM progression and suggests that separate consideration of immunoparesis and the Mayo Clinic risk factors could improve identification of MGUS patients at high risk for progression. [ABSTRACT FROM AUTHOR]

Abstract: Monoclonal κ and λ immunoglobulin free light chain (FLC) paraproteins in serum and urine are important markers in the diagnosis and monitoring of B cell dyscrasias. Current nephelometric and turbidimetric methods that use sheep polyclonal antisera to quantify serum FLC have a number of well-observed limitations. In this report, we describe an improved method using specific mouse anti-human FLC monoclonal antibodies (mAbs). Anti-κ and anti-λ FLC mAbs were, separately, covalently coupled to polystyrene Xmap® beads and assayed, simultaneously, in a multi-plex format by Luminex® (mAb assay). The mAbs displayed no cross-reactivity to bound LC, the alternate LC type, or other human proteins and had improved sensitivity and specificity over immunofixation electrophoresis (IFE) and Freelite™. The assay gives good linearity and sensitivity (<1mg/L), and the competitive inhibition format gave a broad calibration curve up to 437.5mg/L and prevented anomalous results for samples in antigen excess i.e. high FLC levels. The mAbs displayed good concordance with Freelite™ for the quantitation of normal polyclonal FLC in plasma from healthy donors (n=249). The mAb assay identified all monoclonal FLC in serum from consecutive patient samples (n=1000; 50.1% with monoclonal paraprotein by serum IFE), and all FLC in a large cohort of urine samples tested for Bence Jones proteins (n=13090; 22.8% with monoclonal κ, 9.0% with monoclonal λ, and 0.8% with poly LC detected by urine IFE). Importantly this shows that the mAbs are at least close to the ideal of detecting FLC from all patients and neoplastic plasma cell clones. Given the overall effectiveness of the anti-FLC mAbs, further clinical validation is now warranted on serial samples from a range of patients with B cell disorders. Use of these mAbs on other assay platforms should also be investigated. [Copyright &y& Elsevier]

Abstract: The measurement of antibody responses to vaccination is useful in the assessment of immune status in suspected immune deficiency. Previous reliance on enzyme-linked immunoabsorbent assays (ELISA) has been cumbersome, time-consuming and expensive. The availability of flow cytometry systems has led to the development of multiplexed assays enabling simultaneous measurement of antibodies to several antigens. We optimized a flow cytometric bead-based assay to measure IgG and IgM concentrations in serum to 19 antigens contained in groups of bacterial subunit vaccines: pneumococcal vaccines, meningococcal vaccines, Haemophilus influenzae b (Hib), and tetanus and diphtheria toxoid vaccines. 89-SF was employed as the standard serum. The assay was used to determine specific antibody levels in serum from 193 healthy adult donors. IgG and pneumococcal IgM antibody concentrations were measurable across 3 log10 ranges encompassing the threshold protective IgG antibody levels for each antigen. There was little interference between antibody measurements by the 19-plexed assay compared with monoplexed assays, and a lack of cross-reactive IgG antibody, but evidence for cross-reacting IgM antibody for 3/19 pneumococcal antigens. 90th centile values for 15/19 IgG concentrations and 12/12 IgM concentrations of the 193 adult sera were within these ranges and percentages of sera containing protective IgG antibody levels varied from 4% to 95% depending on antigen. This multiplexed assay can simultaneously measure antibody levels to 19 bacterial vaccine antigens. It is suitable for use in standard clinical practice to assess the in vivo immune response to test vaccinations and measure absolute antibody levels to these antigens. [Copyright &y& Elsevier]

Abstract: Acute exercise prior to vaccination can improve the antibody response to influenza vaccination. However, both the optimal exercise protocol and the mechanisms underpinning this adjuvant effect remain unclear. The aim of the current study was to determine whether exercise intensity influenced the efficacy of the intervention. One hundred and sixty healthy young adults were randomly assigned to a resting control group or one of three intervention groups, who exercised at an intensity of 60%, 85%, or 110% of their pre-determined concentric one repetition maxima. The exercise groups performed 50 repetitions of the eccentric portion of both bicep curl and lateral raise movements. All participants then immediately received a reduced dose (50% recommended dose) influenza vaccine. Antibody titres to the three viral strains contained in the vaccine were measured at baseline and at 28days post-vaccination. Compared to the control group, exercise enhanced the antibody response to the least immunogenic of the three strains (B/Florida). In addition, the exercise groups showed an augmented response to the A/Uruguay strain compared to control; however, this effect was observed only in men. The intervention had no effect on the antibody responses to the most immunogenic strain, A/Brisbane. Finally, antibody responses were unrelated to the intensity of the exercise bout. In conclusion, our findings provide further evidence of exercise as an adjuvant to enhance vaccination responses. The results further show that responses to the low-immunogenic antigens are particularly responsive to augmentation by acute eccentric exercise. [Copyright &y& Elsevier]

Nontyphoidal Salmonellae are a major cause of life-threatening bacteremia among HIV-infected individuals. Although cell-mediated immunity controls intracellular infection, antibodies protect against Salmonella bacteremia. We report that high-titer antibodies specific for Salmonella lipopolysaccharide (LPS) are associated with a lack of Salmonella-killing in HIV-infected African adults. Killing was restored by genetically shortening LPS from the target Salmonella or removing LPS-specific antibodies from serum. Complement-mediated killing of Salmonella by healthy serum is shown to be induced specifically by antibodies against outer membrane proteins. This killing is lost when excess antibody against Salmonella LPS is added. Thus, our study indicates that impaired immunity against nontyphoidal Salmonella bacteremia in HIM infection results from excess inhibitory antibodies against Salmonella LPS, whereas serum killing of Salmonella is induced by antibodies against outer membrane proteins. [ABSTRACT FROM AUTHOR]

Nontyphoidal strains of Salmonella (NTS) are a common cause of bacteremia among African children. Cell-mediated immune responses control intracellular infection, but they do not protect against extracellular growth of NTS in the blood. We investigated whether antibody protects against NTS bacteremia in Malawian children, because we found this condition mainly occurs before 2 years of age, with relative sparing of infants younger than 4 months old. Sera from all healthy Malawian children tested aged more than 16 months contained anti-Salmonella antibody and successfully killed NTS. Killing was mediated by complement membrane attack complex and not augmented in the presence of blood leukocytes. Sera from most healthy children less than 16 months old lacked NTS-specific antibody, and sera lacking antibody did not kill NTS despite normal complement function. Addition of Salmonella-specific antibody, but not mannose-binding lectin, enabled NTS killing. All NTS strains tested had long-chain lipopolysaccharide and the rck gene, features that resist direct complement-mediated killing. Disruption of lipopolysaccharide biosynthesis enabled killing of NTS by serum lacking Salmonella-specific antibody. We conclude that Salmonella-specific antibody that overcomes the complement resistance of NTS develops by 2 years of life in Malawian children. This finding and the age-incidence of NTS bacteremia suggest that antibody protects against NTS bacteremia and support the development of vaccines against NTS that induce protective antibody. [ABSTRACT FROM AUTHOR]

• Salivary FLC were significantly decreased in relation to an exam period. • Salivary IgA also decreased while cortisol increased. • Depression and anxiety increased and well-being decreased at exams. • Salivary FLCs are responsive to life events stress and corroborate with IgA. • FLCs may serve as a new salivary biomarker in stress research. Measurement of immunoglobulin free light chains (FLCs) in saliva can serve as a non-invasive biomarker in health and behavioural research. FLCs have been explored in relation to physiological stress but FLC responses to psychological stress and their relationship with infections remain unknown. This study aimed to investigate the impact of exam period stress on salivary FLCs alongside other established biomarkers of stress and whether FLCs relate to symptoms of infection. 58 healthy adults studying at university completed saliva samples and questionnaires in a period without exams (baseline), and again prior to the start of an exam period. Saliva samples were assessed for FLCs, IgA, cortisol and dehydroepiandrosterone (DHEA). Measures of life events stress, perceived stress, anxiety and depression were completed. Students also reported incidence and severity of symptoms of infection and rated general well-being at baseline, prior to, during and after the exam period. Exercise, sleep and alcohol consumption were also assessed at both timepoints. FLCs secretion rates were significantly lower at the exam period compared to baseline (p <.01), with reductions of 26% and 25% for κ FLC and λ FLC, respectively. In agreement, salivary IgA secretion rate was lower at exams (non-significant trend, p =.07). Cortisol concentration significantly increased at exams (p <.05) while DHEA did not change, leading to an increase in the cortisol:DHEA ratio (p =.06). Depression (p <.05) and anxiety increased from baseline to exams and life stress reported in the build up to the exam period was higher compared with baseline (p <.001). Well-being significantly decreased from baseline to exams (p <.01). The proportion of participants reporting infection symptoms (70%) was unchanged between baseline and prior to exams. No significant relationships were found between FLCs or other saliva parameters and infection symptoms, well-being or stress/psychological measures. Changes in saliva parameters between timepoints were independent of health behaviours. Salivary FLCs are responsive to life events stress and corroborate with IgA. This preliminary study highlights the potential utility of FLCs as a new salivary biomarker in stress research. [ABSTRACT FROM AUTHOR]

Bence Jones protein in urine (immunoglobulin free-light-chains) is characteristic of light-chain multiple myeloma. We aimed to compare a quantitative immunoassay for serum free-light-chains with urine tests. Of 224 patients with light-chain myeloma tested at entry to clinical trials, all were correctly identified from serum samples. During monitoring of 82 patients, changes in serum and urine free-light-chains corresponded, but urine became negative for free-light-chains in 26 patients, whereas it remained abnormal in serum in 73 patients. Serum assays could replace Bence Jones protein urine tests for patients with light-chain multiple myeloma. [ABSTRACT FROM AUTHOR]