Test Catalog

Test Id : AB2GP

Beta-2 Glycoprotein 1 Antibodies, IgA, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

Evaluating patients with suspected antiphospholipid syndrome by identification of beta-2 glycoprotein 1 IgA antibodies

 

Evaluating patients at-risk for antiphospholipid syndrome (APS) who are negative for criteria APS tests

 

Estimating the risk of thrombosis and/or pregnancy-related morbidity in patients with systemic lupus erythematosus

Method Name
A short description of the method used to perform the test

Enzyme-Linked Immunosorbent Assay (ELISA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Beta 2 GP1 Ab IgA, S

Aliases
Lists additional common names for a test, as an aid in searching

B2GP1 (Beta-2 Glycoprotein 1)

Specimen Type
Describes the specimen type validated for testing

Serum

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 0.5 mL

Collection Instructions: Centrifuge and aliquot serum into a plastic vial.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.4 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 21 days
Frozen 21 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Evaluating patients with suspected antiphospholipid syndrome by identification of beta-2 glycoprotein 1 IgA antibodies

 

Evaluating patients at-risk for antiphospholipid syndrome (APS) who are negative for criteria APS tests

 

Estimating the risk of thrombosis and/or pregnancy-related morbidity in patients with systemic lupus erythematosus

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or specific pregnancy-related death. Based on the 2006 revised Sapporo consensus classification criteria, the laboratory requirements for diagnosing APS include the presence of at least one of the following: lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-beta-2 glycoprotein 1 (B2GP1) IgG or IgM antibodies.(1). To avoid overdiagnosis, and to exclude patients with transient antiphospholipid (aPL) levels, the APS guidance also recommends confirmation of any positive result at least 12 weeks after the initial evaluation. Of note, aPL antibodies also occur in patients with autoimmune diseases with significant prevalence in systemic lupus erythematosus (SLE) as well as other clinical manifestations (eg, heart valve disease, livedo reticularis, thrombocytopenia, nephropathy, and neurological) often associated with APS.(1-3) Thus, in addition to the 2006 APS guidance, the 2012 derivation and validation of the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE recommends testing for the criteria aPL antibody tests as well as aCL IgA and anti-B2GP1 IgA.(2)

 

B2GP1 is a 326-amino acid protein is synthesized by hepatocytes, endothelial cells and trophoblast cells.(4) It contains 5 repetitive structures or "sushi domains," termed domain 1 through 5, for a combined molecular weight of 54?kDa for the protein.(4-6) Autoantibodies to B2GP1 may detected by solid-phase immunoassays (SPA) and functional coagulation assays. Unlike the LAC, the SPA provides quantitative measurements and antibody isotype class determinations that are important for risk assessment. Immunoassays for B2GP1 antibodies can be performed using either a composite substrate comprised of B2GP1 plus anionic phospholipid (ie, cardiolipin-dependent B2GP1) or B2GP1 alone. Antibodies detected using B2GP1 substrate without another phospholipid (direct assays) are referred to simply as "B2GP1 antibodies." Some B2GP1 antibodies are capable of inhibiting clot formation in functional coagulation assays that contain low concentrations of phospholipid cofactors.(6) Antibodies detected by functional coagulation assays are commonly referred to as LAC. Anti-B2GP1 antibodies associated with thromboembolic events target domain 1 of the molecule and are responsible for LAC (functional, phospholipid-dependent prolongation of the clotting time) and aCL-dependent B2GP1 antibody positivity.(7)

 

For detection of anti-B2GP1 IgG and IgM antibodies, the APS guidance advocates for the use of values above the 99th percentile of the laboratory’s population in the establishment of reference intervals for tests. While this recommendation may be used for anti-B2GP1 IgA immunoassays, there is no consensus for their determination.(6) For aCL IgG and IgM testing, the APS classification guidance recommends antibody cutoff values greater than 40 IgG phospholipid (GPL) or IgM PL (units traceable to the Harris standards for aCL antibody assays) or more than the 99th percentile for the testing laboratory’s population for positivity.(1) The use of cutoff values greater than 40 GPL or MPL units to define positivity is not applicable to all aCL antibody immunoassays as the threshold used to distinguish moderate-to-high positive from low positive results are test dependent.(4,5,7,8) In addition, the cutoff value used at 99th percentile of a laboratory’s testing population may not be consistent with kits from the same manufacturer or 40 GPL units in the case of aCL antibodies.(5-7)

 

Thrombosis and obstetric complications are common clinical events in the general population and are not unique to APS; therefore, the presence of aPL antibodies is an absolute requirement for the diagnosis of definite APS.(1,5,7) Furthermore, aPL antibodies are heterogeneous with overlapping tendencies; the lack of aPL test harmonization or standardization requires the use of all 3 tests for optimal APS diagnosis.(1,5-7) The aPL antibodies were traditionally determined using the classic enzyme-linked immunosorbent assay, with more diverse methods recently developed and adapted for clinical testing. Recognizing the analytical and diagnostic challenges associated with aPL antibody testing, initiatives to support assay harmonization and utilization including the development of calibrators, test development and validation efforts as well as preanalytical, analytical, and postanalytical measures have been published.(5-7) Based on these and other published studies, the interpretation and relevance of aPL antibody tests are dependent on factors such as the type of aPL (LAC, aCL or anti-B2GP1), the source of cardiolipin and/or B2GP1, aPL antibody class (IgG, IgM or IgA) and level, as well as whether antibody positivity is single, double or triple.(1,5-8)

 

In conclusion, although the APS classification criteria were not established for routine clinical use, in the absence of formal diagnostic guidelines, these have widely been adopted to diagnose or assess risk for APS and the need for treatment or prophylaxis. Therefore, in clinical practice, if suspicion for disease is high but criteria aPL antibody tests are inconclusive or negative, deviation from the APS diagnostic criteria may be justified. This may include testing for non-criteria aPL antibody tests such as the aCL IgA and anti-B2GP1 IgA recommended in 2012 SLICC guidance for SLE and/or evaluation of anti-phosphatidylserine/prothrombin IgG and IgM autoantibodies amongst others.(2,6,8-10)

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

<15.0 SAU (negative)

15.0-39.9 SAU (weakly positive)

40.0-79.9 SAU (positive)

> or =80.0 SAU (strongly positive)

Results are reported in standard IgA anti-beta 2 glycoprotein 1 units (SAU).

 

Reference values apply to all ages.

Interpretation
Provides information to assist in interpretation of the test results

The presence of anti-beta-2 glycoprotein 1 (B2GP1) IgA antibodies may be associated with a diagnosis of antiphospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE). In the absence "criteria" aPL antibodies for APS and diagnostic tests for SLE, isolated B2GP1 IgA must be interpreted with a high degree of caution.

 

Documentation of persistence for anti-B2GP1 IgA, as is the case for criteria B2GP1 IgG and IgM antibodies, would be consistent with best clinical practice.

 

Detection of B2GP1 antibodies is not affected by anticoagulant treatment.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Immunoassays for the detection of antiphospholipid (aPL) antibodies, including beta-2 glycoprotein 1 (B2GP1) may not completely distinguish between autoantibodies specific for antiphospholipid syndrome (APS) and those antibodies produced in response to infectious agents with or without thrombosis. Since these antibodies may be transiently produced, documentation of persistence as outlined for aPL IgG and IgM antibodies in the 2006 revised Sapporo guidance for definite APS is required, see Clinical Information.

 

Comparative studies and interlaboratory proficiency surveys indicate that results of phospholipid antibody tests can be highly variable, and results obtained with different commercial immunoassays may yield different results.(1,5,7,8)

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Miyakis S, Lockshin MD, Atsumi T, et al: International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295-306

2. Petri M, Orbai AM, Alarcon GS, et al: Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012 Aug;64(8):2677-2686

3. Sciascia S, Amigo MC, Roccatello D, Khamashta M: Diagnosing antiphospholipid syndrome: 'extra-criteria' manifestations and technical advances. Nat Rev Rheumatol. 2017 Sep;13(9):548-560

4. Lozier J, Takahashi N, Putnam FW: Complete amino acid sequence of human plasma beta 2-glycoprotein 1. Proc Natl Acad Sci USA. 1984 Jun;81(12):3640-3644. doi: 10.1073/pnas.81.12.3640

5. Lakos G, Favaloro EJ, Harris EN, el al: International consensus guidelines on anticardiolipin and anti-beta2-glycoprotein I testing: report from the 13th International Congress on Antiphospholipid Antibodies. Arthritis Rheum. 2012 Jan;64(1):1-10

6. Audrain MAP, El-Kouri D, Hamidou MA, el al: Value of autoantibodies to beta(2)-glycoprotein 1 in the diagnosis of antiphospholipid syndrome. Rheumatology (Oxford). 2002 May;41(5):550-553

7. Pengo V, Bison E, Denas G, Jose SP, Zoppellaro G, Banzato A: Laboratory diagnostics of antiphospholipid syndrome. Semin Thromb Hemost. 2018 Jul;44(5):439-444

8. Devreese KMJ: Solid phase assays for antiphospholipid antibodies. Semin Thromb Hemost. 2022 Sep;48(6):661-671. doi: 10.1055/s-0042-1744364

9. Abisror N, Nguyen Y, Marozio L, et al: Obstetrical outcome and treatments in seronegative primary APS: data from European retrospective study. RMD Open. 2020 Aug;6(2):0. doi: 10.1136/rmdopen-2020-001340

10. Nakamura H, Oku K, Amengual O, et al: First-line, non-criterial antiphospholipid antibody testing for the diagnosis of antiphospholipid syndrome in clinical practice: a combination of anti-beta 2 -glycoprotein I domain I and anti-phosphatidylserine/prothrombin complex antibodies tests. Arthritis Care Res (Hoboken). 2018 Apr;70(4):627-634

Method Description
Describes how the test is performed and provides a method-specific reference

Purified beta-2 glycoprotein 1 (B2GP1) antigen is bound to the wells of a polystyrene microwell plate under conditions that will preserve the antigen in its native state. Prediluted controls and diluted patient sera are added to separate wells, allowing any B2GP1 IgA antibodies present to bind to the immobilized antigen. Unbound sample is washed away, and an enzyme-labeled antihuman IgA conjugate is added to each well. A second incubation allows the enzyme-labeled antihuman IgA to bind to any patient antibodies that have attached to the microwells. After washing away any unbound enzyme-labeled antihuman IgA, the remaining enzyme activity is measured by adding a chromogenic substrate and measuring the intensity of the color that develops. The assay can be evaluated spectrophotometrically by measuring and comparing the color intensity that develops in the patient wells with that of a 5-point calibration curve. Semiquantitative results are reported in standard IgA anti-B2GP1 units (SAU).(Package insert: QUANTA Lite beta 2 GP1 IgA ELISA. Inova Diagnostics; Revision 19, 07/2020)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Wednesday, Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

4 to 6 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

86146

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
AB2GP Beta 2 GP1 Ab IgA, S 44447-1
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
AB2GP Beta 2 GP1 Ab IgA, S 44447-1

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports

Test Update Resources

Change Type Effective Date
File Definition - Result ID 2023-03-15