IgG Subclass Concentrations in Certified Reference Material 470 and Reference Values for Children and Adults Determined with The Binding Site Reagents

Abstract Background: There is currently no international reference preparation for IgG subclass (IgGSc) quantification. This situation has led to calibration differences among assays and a variety of reference interval values with consequential difficulties in comparing results. We therefore evaluated IgGSc concentrations in Certified Reference Material 470 (CRM 470). Methods: Pure, polyclonal IgG1, -2, -3, and -4 were prepared from a large serum pool for use as primary standards. The IgG mass in each preparation was calculated from amino-acid analysis data. IgGSc concentrations were assessed in CRM 470 by nephelometry with modern analytical techniques, using these reference preparations. Subsequently, IgGSc concentrations were measured in 380 healthy individuals (250 males and 130 females), and age-dependent reference intervals were established. Results: IgGSc concentrations in CRM 470 were as follows: IgG1, 5028 mg/L; IgG2, 3418 mg/L; IgG3, 579 mg/L, and IgG4, 381 mg/L, with a total IgG concentration of 9406 mg/L, 2.83% below the certified total IgG value of 9680 mg/L. Age-dependent percentile curves for the four IgGSc were constructed using a Box–Cox transformation. Maximum median values were as follows: IgG1, 6.02 g/L at 11 years; IgG2, 3.45 g/L at 31 years; IgG3, 0.63 g/L at 17 years; and IgG4, 0.48 g/L at 14 years. No significant sex-related differences were observed. Conclusions: The correlation between the summation of individual IgGSc and separate measurements of total IgG concentrations was good and supports the accuracy of the results. The results are based on The Binding Site assays and should not be considered appropriate for other assays unless so demonstrated.

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Variable and inaccurate serum IgG4 levels resulting from lack of standardization in IgG subclass assay calibration

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-0261 ◽

2019 ◽

Vol 57 (11) ◽

pp. 1777-1783 ◽

Cited By ~ 2

Author(s):

Luca Bernasconi ◽

Esther Mundwiler ◽

Stephan Regenass ◽

Vincent Aubert ◽

Angelika Hammerer-Lercher ◽

...

Keyword(s):

Reference Material ◽

Binding Site ◽

Certified Reference Material ◽

Recent Literature ◽

Elevated Serum ◽

Method Comparison ◽

Igg Subclasses ◽

Igg Subclass ◽

Serum Igg4 ◽

Assay Result

Abstract Background The quantification of serum IgG4 is commonly performed during the diagnostic workup of IgG4-related diseases (IgG4-RD). According to recent literature, IgG4 values above 1.35 g/L are characteristic of IgG4-RD and support its diagnosis at initial presentation. The purpose of this study was to evaluate comparability and accuracy of the two main commercially available IgG4 assays (Siemens Healthineers and The Binding Site). Methods Method comparison was performed for IgG and IgG subclasses using a collective of selected samples with elevated serum IgG4. In addition, we assessed the accuracy of both assays using purified polyclonal and monoclonal IgG4 preparations. Results Our data show significant discrepancies between the two IgG subclass assays for the measurement of IgG4 and, to a lesser extent, IgG3. Conclusions The lack of standardization between the two main providers of commercially available IgG4 assays leads to significant inter-assay result discrepancies, which might potentially cause unnecessary clinical workup. We conclude that serum IgG4 assay-specific decision limits, and not an assay-independent single cut-off level for IgG4 (e.g. 1.35 g/L), should be used when assessing patients for IgG4-RD. An internationally recognized, certified reference material for IgG subclasses is urgently needed, and assay manufactures are encouraged to undertake steps toward standardization of measurements of IgG4 and other IgG subclasses.

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Indirect methods for reference interval determination – review and recommendations

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2018-0073 ◽

2018 ◽

Vol 0 (0) ◽

Cited By ~ 6

Author(s):

Graham R.D. Jones ◽

Rainer Haeckel ◽

Tze Ping Loh ◽

Ken Sikaris ◽

Thomas Streichert ◽

...

Keyword(s):

Clinical Chemistry ◽

Direct Methods ◽

Analytical Techniques ◽

Reference Interval ◽

Reference Population ◽

Reference Intervals ◽

Statistical Techniques ◽

Indirect Methods ◽

Indirect Approach ◽

Patient Health

Abstract Reference intervals are a vital part of the information supplied by clinical laboratories to support interpretation of numerical pathology results such as are produced in clinical chemistry and hematology laboratories. The traditional method for establishing reference intervals, known as the direct approach, is based on collecting samples from members of a preselected reference population, making the measurements and then determining the intervals. An alternative approach is to perform analysis of results generated as part of routine pathology testing and using appropriate statistical techniques to determine reference intervals. This is known as the indirect approach. This paper from a working group of the International Federation of Clinical Chemistry (IFCC) Committee on Reference Intervals and Decision Limits (C-RIDL) aims to summarize current thinking on indirect approaches to reference intervals. The indirect approach has some major potential advantages compared with direct methods. The processes are faster, cheaper and do not involve patient inconvenience, discomfort or the risks associated with generating new patient health information. Indirect methods also use the same preanalytical and analytical techniques used for patient management and can provide very large numbers for assessment. Limitations to the indirect methods include possible effects of diseased subpopulations on the derived interval. The IFCC C-RIDL aims to encourage the use of indirect methods to establish and verify reference intervals, to promote publication of such intervals with clear explanation of the process used and also to support the development of improved statistical techniques for these studies.

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Nomogram of age-specific anti-Müllerian hormone levels in healthy Egyptian females

PLoS ONE ◽

10.1371/journal.pone.0254858 ◽

2021 ◽

Vol 16 (7) ◽

pp. e0254858

Author(s):

Eman Ahmed El-Attar ◽

Tamer A. Hosny ◽

Kiyoshi Ichihara ◽

Rania N. Bedair ◽

Ahmed Salah El-Din Tork

Keyword(s):

Reference Interval ◽

Reference Intervals ◽

Specific Reference ◽

Clinical Settings ◽

Power Transformation ◽

Serum Samples ◽

Female Age ◽

Age Related ◽

Age Dependent ◽

Age Range

Background Anti-Müllerian hormone (AMH) is an important determinant of ovarian reserve in fertility workups in many clinical settings. Thus, we investigated the age dependent decline in AMH specific to the Egyptian population and sought to establish an age dependent reference interval parametrically. Methods Serum samples were collected from 841 apparently healthy women. AMH was measured using an electro-chemiluminescent technique. Box-Cox power transformation was used to make the AMH distribution Gaussian for parametric derivation of reference intervals. Results Power of 0.4 was found optimal for Gaussian transformation of AMH reference values. We demonstrate the strong negative relation between circulating AMH and female age with Spearman’s correlation coefficient of rS = −0.528. Age-specific reference interval was determined for every 5 years of age from 16 to 49, and nomogram was constructed by smoothing the lines connecting adjacent lower and upper reference limits. Conclusion The age-specific reference intervals and the age-AMH nomogram could be valuable in the clinical practice of in reproductive medicine. To our knowledge, this is the first study to confirm AMH levels in Egyptian females. We were able to explore age-related AMH levels specific to Egyptian females in the fertile age group and to treat skewed AMH data in a multi-step scheme using power transformation. Thus, a more accurate nomogram was constructed accommodating a profile delineated for a wide age range and a rescaled AMH axis improving its usability.

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Qualitative identification of impurities and principal component quantitative analysis of zearalanone on purity certified reference material

Chinese Journal of Chromatography ◽

10.3724/sp.j.1123.2019.04028 ◽

2019 ◽

Vol 37 (8) ◽

pp. 911

Author(s):

Mengyu FENG ◽

Shuan LIU ◽

Yan GAO ◽

Shukun ZHOU ◽

Zhen GUO ◽

...

Keyword(s):

Quantitative Analysis ◽

Reference Material ◽

Certified Reference Material ◽

Principal Component

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Simplified process of candidate certified reference material development for the analysis of Andrographis paniculata derived therapeutics

Microchemical Journal ◽

10.1016/j.microc.2021.106140 ◽

2021 ◽

pp. 106140

Author(s):

Iti Gaur ◽

Pooja Gaur ◽

Parul Gautam ◽

Neerja Tiwari ◽

Puja Khare ◽

...

Keyword(s):

Reference Material ◽

Certified Reference Material ◽

Andrographis Paniculata ◽

Material Development

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EXPRESS: Method dependent variation in TSH and FT4 reference intervals in pregnancy: a systematic review

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/00045632211026955 ◽

2021 ◽

pp. 000456322110269

Author(s):

O E Okosieme ◽

Medha Agrawal ◽

Danyal Usman ◽

Carol Evans

Keyword(s):

Systematic Review ◽

Reference Interval ◽

First Trimester ◽

Reference Intervals ◽

Assay Method ◽

Specific Reference ◽

Upper Limits ◽

Wide Range ◽

Assay Methods ◽

In Pregnancy

Background: Gestational TSH and FT4 reference intervals may differ according to assay method but the extent of variation is unclear and has not been systematically evaluated. We conducted a systematic review of published studies on TSH and FT4 reference intervals in pregnancy. Our aim was to quantify method-related differences in gestation reference intervals, across four commonly used assay methods, Abbott, Beckman, Roche, and Siemens. Methods: We searched the literature for relevant studies, published between January 2000 and December 2020, in healthy pregnant women without thyroid antibodies or disease. For each study, we extracted trimester-specific reference intervals (2.5â97.5 percentiles) for TSH and FT4 as well as the manufacturer provided reference interval for the corresponding non-pregnant population. Results: TSH reference intervals showed a wide range of study-to-study differences with upper limits ranging from 2.33 to 8.30 mU/L. FT4 lower limits ranged from 4.40â13.93 pmol/L, with consistently lower reference intervals observed with the Beckman method. Differences between non-pregnant and first trimester reference intervals were highly variable, and for most studies the TSH upper limit in the first trimester could not be predicted or extrapolated from non-pregnant values. Conclusions: Our study confirms significant intra and inter-method disparities in gestational thyroid hormone reference intervals. The relationship between pregnant and non-pregnant values is inconsistent and does not support the existing practice in some laboratories of extrapolating gestation references from non-pregnant values. Laboratories should invest in deriving method-specific gestation reference intervals for their population.

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Evaluation of Thyroid Function in Pregnant Women Using Automated Immunoassays

Clinical Chemistry ◽

10.1093/clinchem/hvab009 ◽

2021 ◽

Author(s):

K Aaron Geno ◽

Matthew S Reed ◽

Mark A Cervinski ◽

Robert D Nerenz

Keyword(s):

Pregnant Women ◽

Equilibrium Dialysis ◽

Reference Interval ◽

First Trimester ◽

Reference Intervals ◽

Free Thyroxine ◽

Specific Reference ◽

Childbearing Age ◽

Thyroid Autoantibody ◽

The Impact

Abstract Introduction Automated free thyroxine (FT4) immunoassays are widely available, but professional guidelines discourage their use in pregnant women due to theoretical under-recoveries attributed to increased thyroid hormone binding capacity and instead advocate the use of total T4 (TT4) or free thyroxine index (FTI). The impact of this recommendation on the classification of thyroid status in apparently euthyroid pregnant patients was evaluated. Methods After excluding specimens with thyroid autoantibody concentrations above reference limits, thyroid-stimulating hormone (TSH), FT4, TT4, and T-uptake were measured on the Roche Cobas® platform in remnant clinical specimens from at least 147 nonpregnant women of childbearing age and pregnant women at each trimester. Split-sample comparisons of FT4 as measured by the Cobas and equilibrium dialysis were performed. Results FT4 decreased with advancing gestational age by both immunoassay and equilibrium dialysis. TSH declined during the first trimester, remained constant in the second, and increased throughout the third, peaking just before delivery. Interpretation of TT4 concentrations using 1.5-times the nonpregnant reference interval classified 13.6% of first trimester specimens below the lower reference limit despite TSH concentrations within trimester-specific reference intervals. Five FTI results from 480 pregnant individuals (about 1.0%) fell outside the manufacturer’s reference interval. Conclusions Indirect FT4 immunoassay results interpreted in the context of trimester-specific reference intervals provide a practical and viable alternative to TT4 or FTI. Declining FT4 and increasing TSH concentrations near term suggest that declining FT4 is not an analytical artifact but represents a true physiological change in preparation for labor and delivery.

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Reference values of plasma homocysteine in Cuban children and adults

LaboratoriumsMedizin ◽

10.1515/labmed-2019-0195 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Alina Concepción Alvarez ◽

Ivette Camayd Viera ◽

Lisy Vento Buigues ◽

Yanet Fernández Martínez ◽

Eraida Hernández ◽

...

Keyword(s):

Reference Values ◽

High Performance ◽

Age Groups ◽

Coffee Consumption ◽

Reference Interval ◽

Reference Intervals ◽

Multifactorial Diseases ◽

Weak Association ◽

Different Populations ◽

Cuban Population

AbstractObjectivesHomocysteine (Hcy) is a nonessential amino acid, produced by the demethylation of methionine. High Hcy levels, or hyperhomocysteinemia, have been associated with genetic and multifactorial diseases. Hcy reference values may vary between different populations, as Hcy levels are affected by factors such as sex, age, diet, smoking, and coffee consumption. The estimation reference interval (RI) allows to establish the normal values of this marker in population. At present, these levels are unknown in Cuba. The aim of this work is to estimate the Hcy reference intervals in Cuban children and adults.MethodsTotal Hcy concentration was quantified by high performance liquid chromatography (HPLC) in plasma. Hcy levels were evaluated in samples from 507 healthy individuals (260 children, 247 adults).ResultsRIs were estimated by nonparametric methods. We found significant differences between both age groups, but we did not find significant differences between sexes, within these groups. The established ranges were 2.56–14.55 µM and 3.63–17.19 µM for children and adults, respectively. Also, we observed a weak association between Hcy levels and age in both sex groups.ConclusionsThis is the first study that assesses Hcy reference values in Cuban population. Our results will allow the introduction of Hcy as a biochemical marker in laboratory testing.

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Reference intervals for venous blood gas measurement in adults

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-1224 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Kirsty L. Ress ◽

Gus Koerbin ◽

Ling Li ◽

Douglas Chesher ◽

Phillip Bwititi ◽

...

Keyword(s):

Partial Pressure ◽

Meta Analysis ◽

Venous Blood ◽

Reference Interval ◽

Reference Intervals ◽

Published Data ◽

Blood Gas ◽

Arterial Blood Gas ◽

Arterial Blood ◽

Venous Blood Gas

AbstractObjectivesVenous blood gas (VBG) analysis is becoming a popular alternative to arterial blood gas (ABG) analysis due to reduced risk of complications at phlebotomy and ease of draw. In lack of published data, this study aimed to establish reference intervals (RI) for correct interpretation of VBG results.MethodsOne hundred and 51 adult volunteers (101 females, 50 males 18–70 y), were enrolled after completion of a health questionnaire. Venous blood was drawn into safePICO syringes and analysed on ABL827 blood gas analyser (Radiometer Pacific Pty. Ltd.). A non-parametric approach was used to directly establish the VBG RI which was compared to a calculated VBG RI based on a meta-analysis of differences between ABG and VBGResultsAfter exclusions, 134 results were used to derive VBG RI: pH 7.30–7.43, partial pressure of carbon dioxide (pCO2) 38–58 mmHg, partial pressure of oxygen (pO2) 19–65 mmHg, bicarbonate (HCO3−) 22–30 mmol/L, sodium 135–143 mmol/L, potassium 3.6–4.5 mmol/L, chloride 101–110 mmol/L, ionised calcium 1.14–1.29 mmol/L, lactate 0.4–2.2 mmol/L, base excess (BE) −1.9–4.5 mmol/L, saturated oxygen (sO2) 23–93%, carboxyhaemoglobin 0.4–1.4% and methaemoglobin 0.3–0.9%. The meta-analysis revealed differences between ABG and VBG for pH, HCO3−, pCO2 and pO2 of 0.032, −1.0 mmol/L, −4.2 and 39.9 mmHg, respectively. Using this data along with established ABG RI, calculated VBG RI of pH 7.32–7.42, HCO3− 23 – 27 mmol/L, pCO2 36–49 mmHg (Female), pCO2 39–52 mmHg (Male) and pO2 43–68 mmHg were formulated and compared to the VBG RI of this study.ConclusionsAn adult reference interval has been established to assist interpretation of VBG results.

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