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Reference standards for the detection of anti-mitochondrial and anti-rods/rings autoantibodies

  • S. John Calise , Bing Zheng , Tomoko Hasegawa , Minoru Satoh , Natasa Isailovic , Angela Ceribelli , Luis E.C. Andrade , Katherine Boylan , Ilaria Cavazzana , Marvin J. Fritzler , Ignacio Garcia de la Torre , Falk Hiepe , Kathryn Kohl , Carlo Selmi , Yehuda Shoenfeld , Angela Tincani , Edward K.L. Chan EMAIL logo and the IUIS Autoantibody Standardization Committee
Published/Copyright: February 26, 2018
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 56 Issue 10

Abstract

Background:

Anti-mitochondrial antibodies (AMA) are found in >90% of primary biliary cholangitis patients. Anti-rods/rings antibodies (anti-RR) are most commonly associated with interferon-α and ribavirin treatment in hepatitis C patients. Clinical laboratories routinely screen for AMA and anti-RR using indirect immunofluorescence on HEp-2 cells (HEp-2-IFA). Therefore, we sought to establish reference materials for use in AMA and anti-RR testing.

Methods:

AMA-positive and anti-RR-positive human plasma samples (AMA-REF and RR-REF), identified as potential reference materials based on preliminary data, were further validated by multiple laboratories using HEp-2-IFA, immunoprecipitation (IP), western blotting, IP-western, line immunoassay (LIA), addressable laser bead immunoassay (ALBIA) and enzyme-linked immunosorbent assay (ELISA).

Results:

AMA-REF showed a strong positive cytoplasmic reticular/AMA staining pattern by HEp-2-IFA to ≥1:1280 dilution and positive signal on rodent kidney/stomach/liver tissue. AMA-REF reacted with E2/E3, E3BP, E1α and E1β subunits of the pyruvate dehydrogenase complex by IP and western blotting and was positive for AMA antigens by LIA, ALBIA and ELISA. RR-REF showed a strong positive rods and rings staining pattern by HEp-2-IFA to ≥1:1280 dilution. RR-REF reacted with inosine monophosphate dehydrogenase by IP, IP-western and ALBIA. RR-REF also produced a nuclear homogenous staining pattern by HEp-2-IFA, immunoprecipitated proteins associated with anti-U1RNP antibody and reacted weakly with histones, nucleosomes, Sm and nRNP/Sm by LIA.

Conclusions:

AMA-REF and RR-REF are useful reference materials for academic or commercial clinical laboratories to calibrate and establish internal reference standards for immunodiagnostic assays. AMA-REF and RR-REF are now available for free distribution to qualified laboratories through Plasma Services Group.

Keywords: anti-mitochondrial antibody; anti-rods/rings antibody; autoantibody; autoimmunity; hepatitis C; primary biliary cholangitis
Corresponding author: Professor Edward K.L. Chan, Department of Oral Biology, University of Florida, 1395 Center Drive, Gainesville, FL 32610-0424, USA, Phone: (+1) 352-273-8849; Fax: (+1) 352-273-8829
aThe IUIS Autoantibody Standardization Committee:www.AutoAb.org; echan@ufl.edu

Acknowledgments

The authors would like to thank Nice Carabellese, Franco Franceschini, Boris Gilburd, Haiyan Hou, Justin Nicholas and Meifeng Zhang for their technical support.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: SJC is supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1315138 and was previously supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under Award No. 2T90DE021990-06 while this work was performed. MS is supported by JSPS KAKENHI (Grants-in-Aid for Scientific Research) grant number 15K08790. MJF is a coinvestigator on the UCAN-CANDU project funded by the Canadian Institutes of Health Research. IGDLT receives support from the Mexican National Research System (SNI) from Conacyt (National Council of Science and Technology). CS is supported by the Italian Ministry of Foreign Affairs (PGR00807) and receives research funding from AESKU.Diagnostics GmbH and Menarini Diagnostics (Florence, Italy). The IUIS Autoantibody Standardization Committee has received unrestricted grants from Bio-Rad, Inova Diagnostics and Euroimmun. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation or the National Institutes of Health.

  3. Employment or leadership: None declared.

  4. Honorarium: LECA has received speaking honoraria from Inova Diagnostics and Werfen International (Barcelona, Spain). MJF has received speaking honoraria from Inova Diagnostics, Werfen International, Amgen Canada (Mississauga, ON, Canada) and Alexion Pharmaceuticals (New Haven, CT, USA). CS has received speaking honoraria from AESKU.Diagnostics GmbH, Menarini Diagnostics and Grifols (Barcelona, Spain). AC and EKLC have also received speaking honoraria from Grifols.

  5. Competing interests: MJF was and/or continues to be a consultant to Inova Diagnostics, Werfen International, Alexion Pharmaceuticals and Bio-Rad. CS is a consultant for AESKU.Diagnostics GmbH and Grifols. The funding organizations played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2017-12-10
Accepted: 2018-01-24
Published Online: 2018-02-26
Published in Print: 2018-09-25

©2018 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Harmonization in laboratory medicine: Blowin’ in the wind
  4. Standardization and harmonization of autoimmune diagnostics
  5. On the complexity of hemostasis and the need for harmonization of test practice
  6. Harmonization of laboratory hematology: a long and winding journey
  7. Section 1: Current Harmonization Activities at Global Level
  8. Harmonization in laboratory medicine: more than clinical chemistry?
  9. Harmonization of External Quality Assessment Schemes and their role – clinical chemistry and beyond
  10. An overview of EFLM harmonization activities in Europe
  11. Metrological traceability and harmonization of medical tests: a quantum leap forward is needed to keep pace with globalization and stringent IVD-regulations in the 21st century!
  12. Assessment of bone turnover in osteoporosis: harmonization of the total testing process
  13. Recent initiatives in harmonization of hemostasis practice
  14. EASI – European Autoimmunity Standardisation Initiative: facing the challenges of diagnostics in autoimmunity
  15. Harmonization of microbiology processes and standards: work in progress
  16. Harmonization initiatives in the generation, reporting and application of biological variation data
  17. Harmonization of accreditation to ISO15189
  18. External quality assessment programs in the context of ISO 15189 accreditation
  19. Section 2: Pre-Pre and Pre-Analytical Phase
  20. Laboratory testing in the emergency department: an Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) and Academy of Emergency Medicine and Care (AcEMC) consensus report
  21. The EFLM strategy for harmonization of the preanalytical phase
  22. Section 3: The Analytical Phase
  23. The roadmap for harmonization: status of the International Consortium for Harmonization of Clinical Laboratory Results
  24. The quest for equivalence of test results: the pilgrimage of the Dutch Calibration 2.000 program for metrological traceability
  25. Current state and recommendations for harmonization of serum/plasma 17-hydroxyprogesterone mass spectrometry methods
  26. International normalized ratio (INR) testing in Europe: between-laboratory comparability of test results obtained by Quick and Owren reagents
  27. Detecting molecular forms of antithrombin by LC-MRM-MS: defining the measurands
  28. A design for external quality assessment for the analysis of thiopurine drugs: pitfalls and opportunities
  29. Harmonization of PCR-based detection of intestinal pathogens: experiences from the Dutch external quality assessment scheme on molecular diagnosis of protozoa in stool samples
  30. Harmonization of urine albumin/creatinine ratio (ACR) results: a study based on an external quality assessment program in Polish laboratories
  31. Standardization of autoimmune testing – is it feasible?
  32. Diagnostic laboratory tests for systemic autoimmune rheumatic diseases: unmet needs towards harmonization
  33. Clinically relevant discrepancies between different rheumatoid factor assays
  34. An international survey on anti-neutrophil cytoplasmic antibodies (ANCA) testing in daily clinical practice
  35. Predictive autoimmunity using autoantibodies: screening for anti-nuclear antibodies
  36. Harmonization in autoimmune thyroid disease diagnostics
  37. International consensus on antinuclear antibody patterns: definition of the AC-29 pattern associated with antibodies to DNA topoisomerase I
  38. Reference standards for the detection of anti-mitochondrial and anti-rods/rings autoantibodies
  39. International Consensus on Antinuclear Antibody Patterns: defining negative results and reporting unidentified patterns
https://doi.org/10.1515/cclm-2017-1152
Keywords for this article
anti-mitochondrial antibody; anti-rods/rings antibody; autoantibody; autoimmunity; hepatitis C; primary biliary cholangitis

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Harmonization in laboratory medicine: Blowin’ in the wind
  4. Standardization and harmonization of autoimmune diagnostics
  5. On the complexity of hemostasis and the need for harmonization of test practice
  6. Harmonization of laboratory hematology: a long and winding journey
  7. Section 1: Current Harmonization Activities at Global Level
  8. Harmonization in laboratory medicine: more than clinical chemistry?
  9. Harmonization of External Quality Assessment Schemes and their role – clinical chemistry and beyond
  10. An overview of EFLM harmonization activities in Europe
  11. Metrological traceability and harmonization of medical tests: a quantum leap forward is needed to keep pace with globalization and stringent IVD-regulations in the 21st century!
  12. Assessment of bone turnover in osteoporosis: harmonization of the total testing process
  13. Recent initiatives in harmonization of hemostasis practice
  14. EASI – European Autoimmunity Standardisation Initiative: facing the challenges of diagnostics in autoimmunity
  15. Harmonization of microbiology processes and standards: work in progress
  16. Harmonization initiatives in the generation, reporting and application of biological variation data
  17. Harmonization of accreditation to ISO15189
  18. External quality assessment programs in the context of ISO 15189 accreditation
  19. Section 2: Pre-Pre and Pre-Analytical Phase
  20. Laboratory testing in the emergency department: an Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) and Academy of Emergency Medicine and Care (AcEMC) consensus report
  21. The EFLM strategy for harmonization of the preanalytical phase
  22. Section 3: The Analytical Phase
  23. The roadmap for harmonization: status of the International Consortium for Harmonization of Clinical Laboratory Results
  24. The quest for equivalence of test results: the pilgrimage of the Dutch Calibration 2.000 program for metrological traceability
  25. Current state and recommendations for harmonization of serum/plasma 17-hydroxyprogesterone mass spectrometry methods
  26. International normalized ratio (INR) testing in Europe: between-laboratory comparability of test results obtained by Quick and Owren reagents
  27. Detecting molecular forms of antithrombin by LC-MRM-MS: defining the measurands
  28. A design for external quality assessment for the analysis of thiopurine drugs: pitfalls and opportunities
  29. Harmonization of PCR-based detection of intestinal pathogens: experiences from the Dutch external quality assessment scheme on molecular diagnosis of protozoa in stool samples
  30. Harmonization of urine albumin/creatinine ratio (ACR) results: a study based on an external quality assessment program in Polish laboratories
  31. Standardization of autoimmune testing – is it feasible?
  32. Diagnostic laboratory tests for systemic autoimmune rheumatic diseases: unmet needs towards harmonization
  33. Clinically relevant discrepancies between different rheumatoid factor assays
  34. An international survey on anti-neutrophil cytoplasmic antibodies (ANCA) testing in daily clinical practice
  35. Predictive autoimmunity using autoantibodies: screening for anti-nuclear antibodies
  36. Harmonization in autoimmune thyroid disease diagnostics
  37. International consensus on antinuclear antibody patterns: definition of the AC-29 pattern associated with antibodies to DNA topoisomerase I
  38. Reference standards for the detection of anti-mitochondrial and anti-rods/rings autoantibodies
  39. International Consensus on Antinuclear Antibody Patterns: defining negative results and reporting unidentified patterns
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