Publications by authors named "Jennifer L J Heaney"

24 Publications

  • Page 1 of 1

Anti-bacterial antibodies in multiple myeloma patients at disease presentation, in response to therapy and in remission: implications for patient management.

Blood Cancer J 2020 11 4;10(11):114. Epub 2020 Nov 4.

Institute of Immunology and Immunotherapy, Clinical Immunology Service, University of Birmingham, Birmingham, UK.

Multiple myeloma (MM) is associated with increased risk of infection, but little is known regarding antibody levels against specific bacteria. We assessed levels of polyclonal immunoglobulin and antibacterial antibodies in patients recruited to the TEAMM trial, a randomised trial of antibiotic prophylaxis at the start of anti-myeloma treatment. Polyclonal IgG, IgA and IgM levels were below the reference range in 71%, 83% and 90% of 838 MM patients at diagnosis. Anti-vaccine targeted tetanus toxoid antibodies were protective in 95% of 193 healthy controls but only 41% of myeloma patients. In healthy controls, protective antibodies against 6/12 pneumococcal serotypes, haemophilus and meningococcus A were present in 67%, 41% and 56% compared to just 15%, 21% and 17% of myeloma patients. By 1 year, myeloma patients IgG levels had recovered for 57% of patients whilst the proportion with protective levels of IgG against thymus-dependent protein antigen tetanus toxoid had changed little. In contrast the proportions of patients with protective levels against thymus independent polysaccharide antigens pneumococcus, haemophilus and meningococcus had fallen from 15 to 7%, 21 to 0% and 17 to 11%. Findings highlight the need for strategies to protect patients against bacterial infections during therapy and vaccination programmes during remission.
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http://dx.doi.org/10.1038/s41408-020-00370-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642409PMC
November 2020

Salivary free light chains as a new biomarker to measure psychological stress: the impact of a university exam period on salivary immunoglobulins, cortisol, DHEA and symptoms of infection.

Psychoneuroendocrinology 2020 12 15;122:104912. Epub 2020 Oct 15.

Institute of Immunology and Immunotherapy, University of Birmingham, UK. Electronic address:

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.psyneuen.2020.104912DOI Listing
December 2020

Evaluation of two serum free light chain quantitation methods, Freelite and Seralite, in the clinical laboratory with a view to switching immunoassay.

Clin Chim Acta 2020 Nov 21;510:235-241. Epub 2020 Jul 21.

Clinical Biology Department and INSERM UMR_S 1176, Hospital Foch, Suresnes, France. Electronic address:

Background: Serum free light chain (sFLC) quantitation is central for plasma cell dyscrasias. Several assays are available and switching sFLC methods may be advantageous in certain laboratories. This study performed Freelite and Seralite simultaneously for samples received by the clinical laboratory over a 10 month period and compared quantitation and its impact on interpretation of patient results.

Methods: Patients (N = 189) included multiple myeloma (MM) and related plasma cell cancers, monoclonal gammopathy of unknown significance (MGUS), AL amyloidosis and renal impairment. sFLC quantitation and clinical agreement was assessed between methods.

Results: Clinical agreement was substantial at diagnosis (κ = 0.647, p < .01) and moderate for monitoring (κ = 0.591, p < .01). Good concordance was seen for MM and related plasma disorders and MGUS, with poorer agreement seen for AL amyloidosis. Case studies illustrated agreement in pattern of myeloma disease activity. Bland-Atman plots showed small mean bias but increasing variation between methods with increasing FLC concentrations. Passing-Bablok analysis confirmed systematic differences in quantitation between methods.

Conclusions: Despite differences in quantitation, overall, agreement was seen between the different sFLC platforms in relation to the clinical interpretation. As a rapid test without the need for large and expensive analysers, Seralite may be highly applicable in certain laboratories to enable in-house testing.
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http://dx.doi.org/10.1016/j.cca.2020.07.034DOI Listing
November 2020

Analytical validation of new ELISAs for the quantitation of polyclonal free light chains and comparison to existing assays for healthy and patient samples.

J Immunol Methods 2020 03 26;478:112713. Epub 2019 Nov 26.

Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.

Background: Polyclonal FLCs can be used as a biomarker of inflammation and immune activation in a range of diseases. This study evaluated the performance of new FLC ELISAs (Seralite FLC ELISA) for the quantitation of polyclonal κ and λ FLC, including comparisons to existing assays.

Methods: Technical performance was assessed for the ELISA and reference ranges were generated using healthy donor serum (N = 91). Patients with a range of conditions associated with polyclonal FLC dysregulation (N = 164) were measured across platforms.

Results: The ELISAs generated references ranges of: 8.72-23.0 mg/L κ FLC, and 8.52-25.24 mg/L for λ FLC. ELISAs demonstrated linearity across the calibration range and intra-assay (≤ 8.7%) and inter-assay (≤ 12.3%) imprecision was low. The limit of detection was 0.63 mg/L for κ and 0.57 mg/L for λ FLC. Minimal cross-reactivity was observed for interference agents, alternate FLC and whole immunoglobulin (median change ≤3.6 mg/L). Assays showed good batch-to-batch consistency. For patient samples, methods generated different κ and λ FLC concentrations and differences were seen between methods for the number of patients classified as below, with and above references ranges for κ and λ FLC. There was no significant difference in the FLC sum between the different techniques.

Conclusions: The ELISAs displayed good analytical and technical performance. The quantification of individual κ and λ FLC appears inherently different between platforms. These differences are attenuated if using the FLC sum, which was similar between methods and provided agreement in relation to patients having normal or elevated FLCs.
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http://dx.doi.org/10.1016/j.jim.2019.112713DOI Listing
March 2020

Free light chains as an emerging biomarker in saliva: Biological variability and comparisons with salivary IgA and steroid hormones.

Brain Behav Immun 2020 01 23;83:78-86. Epub 2019 Sep 23.

Institute of Immunology and Immunotherapy, University of Birmingham, UK. Electronic address:

Background: Salivary free light chains (FLCs) are an emerging biomarker in health and behavioural research. However, little is known regarding biological variability of salivary FLCs and how they relate to other established salivary biomarkers. This study aimed to investigate the diurnal and day-to-day variation of salivary FLCs and their relationship with salivary IgA and steroid hormones.

Methods: A total of 46 healthy adults participated in studies exploring the biological variability of FLCs. Diurnal variation was investigated by collecting saliva samples immediately upon waking, 0.5 h, 3 h, 6 h, 9 h and 14 h post-waking. Saliva samples were assessed for FLCs, IgA, cortisol and dehydroepiandrosterone (DHEA). Between-day variation in FLCs and IgA was assessed by collecting saliva samples immediately upon waking for seven consecutive days. Participants underwent a dental examination to exclude oral health as a potential confounding variable. Within and between-person day-to day variation was explored in relation to a range of different factors: awakening time, sleep, exercise, well-being and alcohol consumption.

Results: Salivary secretion rates of FLCs decreased following waking and up to 3 h post-waking and then plateaued. This same pattern was observed for IgA. DHEA was stable upon waking and higher levels were seen in the morning with significantly lower levels thereafter. Cortisol levels significantly increased 0.5 h post-waking then continued to decline across the day. FLCs were significantly correlated with IgA but not cortisol or DHEA. Both FLCs and IgA parameters showed day-to-day variability, with coefficients of variation ≥ 40%. Earlier waking time was significantly correlated with higher FLC and IgA secretion rates. Inter-person differences in saliva parameter variability were observed but the degree of variation in FLCs and IgA was related within person. Inter-person day-to-day variation appeared to be uninfluenced by lifestyle or behavioural factors.

Conclusions: Saliva FLCs secretion exhibits diurnal fluctuation that mirrors IgA fluctuation. Findings strongly indicate salivary FLC secretion is orchestrated by local plasma cells. FLCs and IgA both showed notable variability day-to-day, which was similar within person and influenced by awakening time. FLCs offer a promising adjunct to IgA in the measurement of oral immune activation.
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http://dx.doi.org/10.1016/j.bbi.2019.09.018DOI Listing
January 2020

Characterisation of immunoparesis in newly diagnosed myeloma and its impact on progression-free and overall survival in both old and recent myeloma trials.

Leukemia 2018 08 20;32(8):1727-1738. Epub 2018 Jun 20.

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.

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.
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http://dx.doi.org/10.1038/s41375-018-0163-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087716PMC
August 2018

Intensified training increases salivary free light chains in trained cyclists: Indication that training volume increases oral inflammation.

Physiol Behav 2018 05 7;188:181-187. Epub 2018 Feb 7.

Department for Health, University of Bath, UK.

Periods of short-term intensified training (IT) are often used by athletes during training cycles over the season and undergoing phases of increased physical stress may impact upon the immune system. This study investigated the effects of a period of IT on free light chains (FLCs) in saliva - an emerging immune biomarker of oral inflammation - and matched serum samples in well-trained athletes. It also examined if IT influences basal FLC levels and FLC flux during acute exercise. Highly trained male cyclists (n = 10) underwent a 9-day period of IT; before and after IT participants performed a 1 h time trial (TT) on a cycle ergometer, with blood and saliva samples collected pre- and post-exercise. FLCs were assessed in serum and saliva, and IgG, IgA, IgM and creatinine were also measured in serum. Weekly training volume increased by 143% (95% CI 114-172%), p < 0.001, during IT compared with pre-trial baseline training. Following IT, the cyclists demonstrated higher salivary FLC levels. Both salivary lambda FLC concentrations (p < 0.05, η = 0.384) and secretion rates, and kappa FLC concentrations and secretion rates increased after IT. Salivary FLCs concentration and secretion rates decreased in response to the TT following IT (p < 0.05, η = 0.387-0.428), but not in response to the TT prior to IT. No significant effects of IT on serum FLCs were observed. There were no significant changes in serum FLCs in response to the TT, before or after the IT period, nor did IT impact upon other serological responses to the TT. In conclusion, IT increased basal salivary FLC parameters and amplified decreases in salivary FLCs in response to acute exercise. Increases in salivary FLC concentration likely reflects alterations to oral inflammation during times of heavy training, and we show for the first time that FLCs may have utility as a marker of exercise stress and oral health status.
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http://dx.doi.org/10.1016/j.physbeh.2018.02.013DOI Listing
May 2018

Response comparison of multiple myeloma and monoclonal gammopathy of undetermined significance to the same anti-myeloma therapy: a retrospective cohort study.

Lancet Haematol 2017 Dec 13;4(12):e584-e594. Epub 2017 Nov 13.

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. Electronic address:

Background: Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS), which is usually only treated by a form of anti-multiple myeloma therapy if it is causing substantial disease through deposition of secreted M proteins. However, studies comparing how MGUS and multiple myeloma plasma cell clones respond to these therapies are scarce. Biclonal gammopathy multiple myeloma is characterised by the coexistence of an active multiple myeloma clone and a benign MGUS clone, and thus provides a unique model to assess the responses of separate clones to the same anti-multiple myeloma therapy, in the same patient, at the same time. We aimed to identify how MGUS and multiple myeloma plasma cell clones responded to anti-multiple myeloma therapy in patients newly diagnosed with biclonal gammopathy multiple myeloma.

Methods: In this retrospective cohort study, we identified patients with biclonal gammopathy multiple myeloma by central laboratory analysis of 6399 newly diagnosed patients with multiple myeloma enrolled in three UK clinical trials (Myeloma IX, Myeloma XI, and TEAMM) between July 7, 2004, and June 2, 2015. In addition to the inclusion criteria of these trials, our study necessitated at trial entry the presence of two distinct M proteins in immunofixation electrophoresis. The primary endpoint was difference in response achieved with anti-multiple myeloma therapy on MGUS (which we defined as M2) and multiple myeloma (M1) clones-overall, within patients, and between therapy types-with international therapy response criteria assessed with χ analyses. We analysed by intention to treat.

Findings: 44 patients with biclonal gammopathy multiple myeloma with IgG or IgA MGUS clones were subsequently identified from the three trials and then longitudinally monitored. 41 (93%) of M1 clones had a response to therapy (either complete response, very good partial response, partial response, or minor response) compared with only 28 (64%) of M2 clones (p=0·0010). For the 20 patients who received intensive therapy, there was no difference between the proportion of responding clones in M1 (19 [95%]) and M2 (15 [75%], p=0·13). However, for the 17 patients who received non-intensive therapy, 16 (94%) of M1 clones had a response compared with ten [59%] of M2 clones (p=0·031). When examining clones within the same patient, 30 (68%) of 44 individual patients had different levels of responses within the M1 and M2 clones. One patient exhibited M2 progression to myeloma and subsequently died.

Interpretation: These results show that, in patients with biclonal gammopathy multiple myeloma, anti-multiple myeloma therapies exert a greater depth of response against multiple myeloma plasma cell clones than MGUS plasma cell clones. Although some MGUS clones exhibited a complete response, many did not respond, which suggests that the underlying features that render multiple myeloma plasma cells susceptible to therapy are present in only some MGUS plasma cell clones. To determine MGUS clone susceptibly to therapy, future studies might seek to identify, with biclonal gammopathy multiple myeloma as an investigative model, the genetic and epigenetic alterations that affect whether MGUS plasma cell clones are responsive to anti-multiple myeloma therapy.

Funding: National Institute of Health Research, Medical Research Council, and Cancer Research UK.
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http://dx.doi.org/10.1016/S2352-3026(17)30209-0DOI Listing
December 2017

Multiple myeloma can be accurately diagnosed in acute kidney injury patients using a rapid serum free light chain test.

BMC Nephrol 2017 Jul 20;18(1):247. Epub 2017 Jul 20.

Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK.

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.
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http://dx.doi.org/10.1186/s12882-017-0661-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520226PMC
July 2017

Active multiple myeloma suppresses and typically eliminates coexisting MGUS.

Br J Cancer 2017 Sep 20;117(6):835-839. Epub 2017 Jul 20.

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.

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.
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http://dx.doi.org/10.1038/bjc.2017.229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589985PMC
September 2017

Diagnosis and monitoring for light chain only and oligosecretory myeloma using serum free light chain tests.

Br J Haematol 2017 07 1;178(2):220-230. Epub 2017 Jun 1.

Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.

This study aims to guide the integration of serum free light chain (sFLC) tests into clinical practice, including a new rapid test (Seralite ). Blood and urine analysis from 5573 newly diagnosed myeloma patients identified 576 light chain only (LCO) and 60 non-secretory (NS) cases. Serum was tested by Freelite and Seralite at diagnosis, maximum response and relapse. 20% of LCO patients had urine FLC levels below that recommended for measuring response but >97% of these had adequate sFLC levels (oligosecretory). The recommended Freelite sFLC ≥100 mg/l for measuring response was confirmed and the equivalent Seralite FLC difference (dFLC) >20 mg/l identified. By both methods, ≥38% of NS patients had measurable disease (oligosecretory). Higher sFLC levels were observed on Freelite at all time points. However, good clinical concordance was observed at diagnosis and in response to therapy. Achieving at least a very good partial response according to either sFLC method was associated with better patient survival. Relapse was identified using a Freelite sFLC increase >200 mg/l and found 100% concordance with a corresponding Seralite dFLC increase >30 mg/l. Both Freelite and Seralite sensitively diagnose and monitor LCO/oligosecretory myeloma. Rapid testing by Seralite could fast-track FLC screening and monitoring. Response by sFLC assessment was prognostic for survival and demonstrates the clinical value of routine sFLC testing.
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http://dx.doi.org/10.1111/bjh.14753DOI Listing
July 2017

The utility of saliva for the assessment of anti-pneumococcal antibodies: investigation of saliva as a marker of antibody status in serum.

Biomarkers 2018 Mar 12;23(2):115-122. Epub 2016 Dec 12.

a Clinical Immunology Service, School of Immunity and Infection, University of Birmingham , Birmingham , UK.

Context: Salivary antibodies may act as non-invasive marker of systemic immunity enabling assessment of vaccination and protection against bacterial infections.

Objective: To assess if levels of anti-pneumococcal (Pn) antibodies in saliva reflect concentrations in serum and determine whether saliva can accurately identify protective concentrations in serum.

Methods: IgG, IgA and IgM antibody levels in paired saliva and serum samples were measured against 12 Pn polysaccharide antigens in 72 healthy adults.

Results: Antibody levels in saliva correlated positively with serum across immunoglobulin classes, most strongly for IgA. Individuals who had protective antibody levels in serum demonstrated significantly higher IgG and IgA salivary antibody concentrations/secretion rates. Salivary IgG and IgA Pn antibodies were able to distinguish between those with/without protective levels in serum for the majority of serotypes. Salivary IgM antibodies were not able to differentiate protective status. Median IgG and IgA Pn salivary parameters were able to identify individuals who had protective levels in serum on ≥8/12 serotypes with moderate accuracy: median IgA secretion rates provided the best sensitivity (73%) and specificity (71%).

Conclusions: These findings suggest that IgG and IgA Pn specific antibodies in saliva may be useful surrogate markers of antibody status in serum.
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http://dx.doi.org/10.1080/1354750X.2016.1265009DOI Listing
March 2018

Development of a rapid and quantitative lateral flow assay for the simultaneous measurement of serum κ and λ immunoglobulin free light chains (FLC): inception of a new near-patient FLC screening tool.

Clin Chem Lab Med 2017 Mar;55(3):424-434

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.
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http://dx.doi.org/10.1515/cclm-2016-0194DOI Listing
March 2017

Serum free light chains are reduced in endurance trained older adults: Evidence that exercise training may reduce basal inflammation in older adults.

Exp Gerontol 2016 May 26;77:69-75. Epub 2016 Feb 26.

Clinical Immunology Service, University of Birmingham, Birmingham, UK.

Traditionally, free light chains (FLCs) are used as key serum biomarkers in the diagnosis and monitoring of plasma cell malignancies, but polyclonal FLCs can also be used as an accurate real-time indicator of immune-activation and inflammation. The primary aim of the present study was to assess the effects of exercise training status on serum FLCs in older adults, and secondly, to examine if training status moderated serum FLC responses to acute exercise. Kappa and lambda serum FLC levels were measured in 45 healthy older adults (aged ≥ 60 years) who were either sedentary, physically active or endurance trained. FLCs were measured at baseline and in response to an acute bout of submaximal exercise. The endurance trained group had significantly lower levels of kappa and lambda serum FLCs compared with physically active or sedentary elderly adults; these effects were independent of age, BMI and renal function. There was no significant difference in whole immunoglobulins between groups. Exercise training status had no effect on serum FLC responses to acute exercise, which were marginal. In conclusion, endurance training was associated with lower FLC levels compared with less physically active individuals. These findings suggest that long-term endurance training may be beneficial in reducing basal inflammation in older adults as well as elevated FLCs present in inflammatory and autoimmune conditions, often associated with ageing. FLCs may serve as a useful biomarker for monitoring the efficacy of exercise intervention studies in healthy and clinical populations.
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http://dx.doi.org/10.1016/j.exger.2016.02.011DOI Listing
May 2016

Salivary immunoglobulin free light chains: reference ranges and responses to exercise in young and older adults.

Exerc Immunol Rev 2016;22:28-41

Clinical Immunology Service, University of Birmingham, Birmingham, UK.

Background: Free light chains (FLCs) have a range of biological functions and may act as a broad marker of immunesuppression 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 measuredin 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) concentrationswere 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 ad ults. 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.
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October 2018

Salivary Functional Antibody Secretion Is Reduced in Older Adults: A Potential Mechanism of Increased Susceptibility to Bacterial Infection in the Elderly.

J Gerontol A Biol Sci Med Sci 2015 Dec 31;70(12):1578-85. Epub 2015 Aug 31.

Clinical Immunology Service, School of Immunity and Infection and.

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.
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http://dx.doi.org/10.1093/gerona/glv085DOI Listing
December 2015

Physical activity, life events stress, cortisol, and DHEA: preliminary findings that physical activity may buffer against the negative effects of stress.

J Aging Phys Act 2014 Oct 1;22(4):465-73. Epub 2013 Oct 1.

School of Sport and Exercise Sciences, University of Birmingham, Birmingham, West Midlands, England, UK.

The present study examined the relationship between habitual physical activity, life events stress, the diurnal rhythms of cortisol and DHEA, and the cortisol:dehydroepiandrosterone (DHEA) ratio in older adults. Thirty-six participants aged ≥ 65 reported their habitual physical activity, and indicated if a particular event happened to them in the past year (stress incidence) and how stressful they perceived the event to be (stress severity). Older adults with higher stress severity demonstrated a significantly higher cortisol:DHEA ratio. Individuals with higher stress incidence scores and who did not participate in aerobic exercise had a significantly higher cortisol:DHEA ratio and flatter DHEA diurnal rhythm compared with those who regularly participated in aerobic exercise. In conclusion, life events stress may have a negative impact on the cortisol:DHEA ratio in older adults. Under conditions of high stress exposure, exercise may protect older adults from an increased cortisol:DHEA ratio and flatter DHEA diurnal rhythm.
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http://dx.doi.org/10.1123/japa.2012-0082DOI Listing
October 2014

Aging, health behaviors, and the diurnal rhythm and awakening response of salivary cortisol.

Exp Aging Res 2012 ;38(3):295-314

School of Sport and Exercise Sciences, University of Birmingham, Birmingham, West Midlands, England, UK.

Unlabelled: BACKGROUND/STUDY CONTEXT: The cortisol diurnal rhythm has previously been examined in relation to age and health behaviors. However, less is known about the relationship between multiple health behaviors and diurnal cortisol in the context of aging, where it is possible that the impact of health behaviors on cortisol varies as a function of age. This study compared the awakening response and diurnal rhythm of cortisol in young versus older adults in relation to health behaviors.

Methods: Twenty-four young students (aged 18-22) and 48 community-dwelling older adults (aged 65-88) completed an assessment of health behaviors (exercise, smoking, sleep, diet, alcohol) over the past year. Salivary cortisol was measured over the course of 1 day: immediately upon awakening, 30 min later, and then 3, 6, 9, and 12 h post awakening. Repeated measures/univariate analysis of variance (ANOVA) was used to test main effects of age and health behaviors, and any interaction effects in relation to diurnal cortisol.

Results: Older adults displayed significantly reduced cortisol upon awakening, a lower cortisol awakening response, and a flatter diurnal profile represented by a reduced area under the curve and cortisol slope. There was also a significant interaction of age, cortisol, and diet; younger adults with a higher fat and lower fruit and vegetable intake exhibited the flattened diurnal cortisol phenotype of the older adults.

Conclusion: These findings suggest that the diurnal rhythm and awakening response of salivary cortisol is significantly reduced in older adults and that variations in the cortisol diurnal rhythm of younger adults are associated with dietary factors. Younger adults with a poor quality of food intake may be vulnerable to a reduction in the amplitude of the cortisol diurnal profile and this may have implications for other aspects of health.
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http://dx.doi.org/10.1080/0361073X.2012.672134DOI Listing
August 2012

DHEA, DHEA-S and cortisol responses to acute exercise in older adults in relation to exercise training status and sex.

Age (Dordr) 2013 Apr 22;35(2):395-405. Epub 2011 Nov 22.

School of Sport and Exercise Sciences, University of Birmingham, Birmingham, West Midlands, England, UK, B15 2TT.

The aim of the present study was to investigate resting measures of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEA-S) and cortisol, and the response and recovery of these hormones to acute exercise, in male and female older adults of different exercise training status. Participants were 49 community-dwelling older adults (23 females) aged between 60 and 77 years who were either sedentary (n=14), moderately active (n=14) or endurance trained (n=21). Participants undertook an acute bout of exercise in the form of an incremental submaximal treadmill test. The exercise lasted on average 23 min 49 s (SD=2 min 8 s) and participants reached 76.5% (SD=5.44) of the predicted maximal heart rate. Blood samples were collected prior to exercise, immediately, and 1 h post-exercise. DHEA levels significantly increased immediately post-exercise; however, DHEA-S levels only significantly increased in females. Cortisol significantly decreased immediately post-exercise and 1 h post-exercise compared to pre-exercise. There were no significant differences in resting hormone levels or hormonal responses to exercise between training status groups. The findings suggest that exercise can stimulate DHEA production in older adults and that hormonal responses to exercise differ between male and female older adults.
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http://dx.doi.org/10.1007/s11357-011-9345-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3592957PMC
April 2013

Disordered eating behaviour is associated with blunted cortisol and cardiovascular reactions to acute psychological stress.

Psychoneuroendocrinology 2012 May 29;37(5):715-24. Epub 2011 Sep 29.

School of Sport and Exercise Sciences, University of Birmingham, Birmingham B15 2TT, UK.

Research suggests a potential dysregulation of the stress response in individuals with bulimia nervosa. This study measured both cardiovascular and cortisol reactions to a standardised laboratory stress task in individuals identified as showing disordered eating behaviour to determine whether dysregulation of the stress response is characteristic of the two branches of the stress response system. Female students (N=455) were screened using two validated eating disorder questionnaires. Twelve women with disordered eating, including self-induced vomiting, and 12 healthy controls were selected for laboratory stress testing. Salivary cortisol and cardiovascular activity, via Doppler imaging and semi-automatic blood pressure monitoring, were measured at resting baseline and during and after exposure to a 10-min mental arithmetic stress task. Compared to controls the disordered eating group showed blunted cortisol, cardiac output, heart rate, and stroke volume reactions to the acute stress, as well as an attenuated vasodilatory reaction. These effects could not be accounted for in terms of group differences in stress task performance, subjective task impact/engagement, age, BMI, neuroticism, cardio-respiratory fitness, or co-morbid exercise dependence. Our findings suggest that disordered eating is characterised by a dysregulation of the autonomic stress-response system. As such, they add further weight to the general contention that blunted stress reactivity is characteristic of a number of maladaptive behaviours and states.
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http://dx.doi.org/10.1016/j.psyneuen.2011.09.004DOI Listing
May 2012

Ageing, physical function, and the diurnal rhythms of cortisol and dehydroepiandrosterone.

Psychoneuroendocrinology 2012 Mar 29;37(3):341-9. Epub 2011 Jul 29.

School of Sport and Exercise Sciences, University of Birmingham, Birmingham, West Midlands, B15 2TT, UK.

The present study examined the relationship between ageing, physical function and the diurnal rhythms of cortisol and dehydroepiandrosterone (DHEA). Participants were 36 community dwelling older adults aged between 65 and 86 years old. Salivary cortisol and DHEA were measured over the course of one day: immediately upon awakening, 30 min later, and then 3 h, 6 h, 9 h and 12 h post-awakening. Participants completed the Nottingham extended activities of daily living index, the Berg Balance Scale and their handgrip strength was assessed. Older participants had a significantly higher cortisol area under the curve (AUC), lower overall DHEA levels, lower DHEA AUC, a decreased diurnal slope of decline and increased cortisol:DHEA ratio. Lower diurnal cortisol levels were associated with poorer performance on the Berg Balance Scale and lower handgrip strength, and those with a flattened DHEA diurnal profile reported less independence in carrying out daily tasks. These associations withstood adjustment for age. In conclusion, this study suggests an association between cortisol, DHEA, ageing and physical function.
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http://dx.doi.org/10.1016/j.psyneuen.2011.07.001DOI Listing
March 2012

Preliminary evidence that exercise dependence is associated with blunted cardiac and cortisol reactions to acute psychological stress.

Int J Psychophysiol 2011 Feb 8;79(2):323-9. Epub 2010 Dec 8.

School of Sport and Exercise Sciences, University of Birmingham, UK.

Low or blunted cardiovascular and cortisol reactions to acute psychological stress have been shown to characterise those with a tobacco or alcohol dependency. The present study tested the hypothesis that exercise dependency would be similarly associated with blunted reactivity. Young female exercisers (N=219) were screened by questionnaire for exercise dependence. Ten women with probable exercise dependence and 10 non dependent controls were selected for laboratory stress testing. Cardiovascular activity and salivary cortisol were measured at rest and in response to a 10-min mental arithmetic stress task. The exercise dependent women showed blunted cardiac reactions to the stress task and blunted cortisol at 10, 20, and 30 minute post stress exposure. These effects could not be accounted for in terms of group differences in stress task performance, nor could the cardiac effects be attributed to group differences in cardio-respiratory fitness. It would seem that low stress reactivity is characteristic of a wide range of dependencies, and is not confined to substance dependence. Our results offer further support for the hypothesis that blunted stress reactivity may be a peripheral marker of a central motivational dysregulation.
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http://dx.doi.org/10.1016/j.ijpsycho.2010.11.010DOI Listing
February 2011

Ageing, depression, anxiety, social support and the diurnal rhythm and awakening response of salivary cortisol.

Int J Psychophysiol 2010 Dec 3;78(3):201-8. Epub 2010 Aug 3.

School of Sport and Exercise Sciences, University of Birmingham, Birmingham, West Midlands, England, UK.

The present study compared the cortisol awakening response and diurnal rhythm in 24 young healthy students and 48 community-dwelling older adults. The associations with diurnal cortisol and depression, anxiety and social support were also examined in relation to age. Salivary cortisol was measured over the course of one day: immediately upon awakening, 30 min later, and then 3h, 6h, 9h and 12h post-awakening. Participants completed a questionnaire measuring symptoms of anxiety and depression and social support was assessed. Older adults exhibited a significantly reduced awakening response, overall cortisol levels, area under the curve (AUC) and diurnal slopes than younger adults, resulting in a flatter diurnal rhythm. Younger adults with higher depression scores had significantly higher overall cortisol and higher levels upon awakening and 30 min post-awakening. In the younger adults, anxiety and depression correlated positively with AUC and the cortisol awakening response (CAR). Older adults with lower social support had a reduced AUC where younger adults with lower social support displayed a larger AUC. These findings suggest that the diurnal rhythm and awakening response of salivary cortisol are significantly reduced in older adults and the associations between anxiety, depression and social support and diurnal cortisol vary with age.
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http://dx.doi.org/10.1016/j.ijpsycho.2010.07.009DOI Listing
December 2010