ARUP Immunology Frequently Asked Questions

TNF-alpha inhibitors: Infliximab and Adalimumab

How does ARUP's Infliximab test compare with other tests?
  • The main difference is that ARUP's test measures bioactivity of the drug and of the neutralizing antibody. See table below for comparison of methods to monitor anti-drug antibody (ADA) levels in serum.
    ARUP Infliximab/Adalimumab Assay
      ARUP assy (reporter gene assay) ELISA (solid-phase bridging) Fluid-phase RIA Homogeneous mobility-shift assay (size exclusion HPLC)
    What the test measures Bioactivity Binding Binding Binding
    in vivo relevance to the drug's capacity to inhibit TNF in patient High Low Moderate Moderate
    Specifically detects ADAs with drug-neutralizing function Yes No No No
    Detection of IgG4 antibodies (major isotype of ADAs) Yes No Yes Yes
    Possibility of false negative ADA due to drug in sample Low High Low Low
    Possibility of false positives due to neoepitopes, nonspecific binding, rheumatoid factors, complement components Low High Low Low
What is the precision of measurements of drug and drug-neutralizing antibody in this test?
  • Based on ARUP's internal validation data, the CVs are less than 20% for both the drug and the drug-neutralizing antibody measurements.
The instruction says to test the patient before infliximab or adalimumab treatment. Why? How soon can the test be done after the last infusion?
  • The most effective timing for the test is just prior to the next treatment when the drug level is lowest in the patient (at trough). This is the time when information about drug metabolism can best be determined. Accurate levels of anti-drug antibody (ADA) cannot be measured if the patient is tested immediately after infliximab treatment. The overwhelming amount of drug will absorb the ADAs and will interfere with its detection. This is true with all tests regardless of the methodology used. The minimum amount of time required after the last infusion for testing will depend on the pharmacokinectics and pharmacodynamics of the drug in each patient. In general, it should be at least 72 hours after treatment and we strongly encourage testing right before the next treatment. The bioactivity measurements of the iLite assay used in ARUP's test has a lower possibility of false negative results for ADA measurements compared to traditional methods using solid phase ELISA.

Quantiferon

Why doesn’t ARUP offer the T-SPOT® testing?
  • The T-SPOT® is very difficult to get turned around in the manufacturer indicated stability times. Also the test is manually interpreted, which introduces another concern from a lab perspective in regards to reproducibility. Even with the new “XTend” product that Oxford now sells, it would be nearly impossible for ARUP to get specimens transported, in-house to ARUP, and tested within stability limits set by the FDA approval. If the Quantiferon tubes are collected according to the explicate instructions on our web-site, and transported appropriately we can meet all FDA guidance. Based on the stability issues with the T-SPOT® testing, as well as the variability of manually counting “spots” the decision was made a while ago not to bring this testing into ARUP.
Is there a clinical difference in results between the T-SPOT® and Quantiferon-TB Gold?
  • CDC did a large study and published it in 2012 in which they showed that neither test is sufficiently better than the other. They are both imperfect and require additional follow-up testing in low prevalence populations. In terms of the clinical utility it comes down to convenience and practicality. The Quantiferon assay is more convenient and practical due to the stability issues surrounding the T-SPOT®. Quantiferon-TB Gold and the T-SPOT® are considered equivalent clinically. The T-SPOT® has an equivocal range, which is the only real difference in the test interpretation.

Paraneoplastic Testing - ARUP Consult

How does ARUP testing compare to the extensive panels performed at other laboratories?
  • ARUP offers a comprehensive list of tests that represent the autoantibodies found in about 85-90% of patients with PNS or other autoimmune neurologic disorders (as standalone or in panels). Of the tests not offered by ARUP, the N-type VGCC which overlaps with the P/Q-type VGCC and the ganglionic AChR antibody assays are the most prevalent. Assays for detecting both of these antibodies are currently under development. While other laboratories may offer more tests than ARUP, most of these are very rare and significantly overlap with the readily available tests1,2.

  • 1. Horta ES, Lennon VA, Lachance DH, Jenkins SM, Smith CY, McKeon A, Klein C, Pittock SJ. Neural autoantibody clusters aid diagnosis of cancer. Clin Cancer Res. 2014 Jul 15;20(14):3862-9.
    2. Tebo AE, Haven TR, Jackson BR. Autoantibody diversity in paraneoplastic syndromes and related disorders: The need for a more guided screening approach. Clin Chim Acta. 2016 Aug 1;459:162-9.
Clinically, what does the ARUP test not provide and how do the missing pieces impact the clinical assessment of the patient?
  • ARUP Laboratories offers a significant number of the same tests as our competitors and they are offered as standalone tests or in limited panels. The majority of these have significant clinical impact and may cover 85-90% of the disease cases (unique antibodies). Of the tests not offered by ARUP, the N-type VGCC which overlaps with the P/Q-type VGCC and the ganglionic AChR antibody assays are the most prevalent. Assays for detecting both of these antibodies are currently under development. In addition, there are two categories of tests that cannot be offered by ARUP. The first due to patent issues and the second because of negligible or questionable clinical significance, or they are extremely rare and should only be ordered in limited cases. These include:
    1. Under development (<5% of unique cases)
      • b.  N-Type Calcium Channel Ab
      • c.  AChR Ganglionic Neuronal Ab, S
    2. Restricted by license (<5% of unique cases)
      • a.  Anti-Glial Nuclear Ab, Type 1
    3. Negligible clinical significance or extremely rare (likely less than 1% of unique cases)
      • a.  Anti-Neuronal Nuclear Ab, Type 3
      • b.  Purkinje Cell Cytoplasmic Ab Type 2
      • b.  Purkinje Cell Cytoplasmic Ab Type 3
      • c.  AMPA-R Ab CBA, S
      • d.  GABA-B-R Ab CBA, S
    4. Additional:
      • a.  The N-type VGCC antibody significantly overlaps with the P/Q-type.
      • b.  PCCA-2 and ANNA-3 are both extremely rare with limited clinical relevance.
      • c.  GABA-B-R Ab, AMPA-R Ab and PCCA-3 assays are not currently offered in the ARUP panel. These markers are also very rare with very few cases described since their discovery.
      • d.  ARUP offers VGKC with reflex to LGI1 and CASPR2. This panel is very important, more so than the GABA and AMPA which are less common.
      •  

Panels offered by ARUP :

Panel Test Panel Includes
Autoimmune Encephalitis Reflexive Panel 2013601 N-methyl-D-Aspartate Receptor Antibody, IgG, Serum with Reflex to Titer 2004221
Glutamic Acid Decarboxylase Antibody 2001771
Voltage-Gated Potassium Channel (VGKC) Antibody with Reflex to LGI1 and CASPR2 Screen and Titer 2009463
Aquaporin-4 Receptor Antibody, IgG by IFA with Reflex to Titer, Serum 2013320
Aquaporin-4 Receptor Antibody 203036
Leucine-Rich, Glioma-Inactivated Protein 1 Antibody, IgG with Reflex to Titer 2009456
Contactin-Associated Protein-2 Antibody, IgG with Reflex to Titer 2009452
Autoimmune Neuromuscular Junction Reflective Panel 2005640 Acetylcholine Receptor Binding Antibody 0080009
Acetylcholine Receptor Blocking Antibody 0099580
Acetylcholine Receptor Modulating Antibody 0099521
Voltage-Gated Calcium Channel (VGCC) Antibody 0092628
Voltage-Gated Potassium Channel (VGKC) Antibody with Reflex to LGI1 and CASPR2 Screen and Titer 2009463
Striated Muscle Antibodies, IgG with Reflex to Titer 0050746
Titin Antibody 2005636
Leucine-Rich, Glioma-Inactivated Protein 1 Antibody, IgG and Contactin-Associated Protein-2 Antibody, IgG with Reflex to Titers 2009460
Paraneoplastic Reflexive Panel 2013955 Paraneoplastic Antibodies (PCCA/ANNA) by IFA with Reflex to Titer and Immunoblot 2007961 (immunoblot tests for Hu, Ri and Yo)
Amphiphysin Antibody, IgG 2008893
CV2.1 Screen by IFA with Reflex to Titer 2013956
Autoimmune Neurologic Disease Comprehensive Panel 2013944 Paraneoplastic Antibodies (PCCA/ANNA) by IFA with Reflex to Titer and Immunoblot 2007961 (immunoblot tests for Hu, Ri and Yo)
Amphiphysin Antibody, IgG 2008893
CV2.1 Antibody, IgG, Serum with Reflex to Titer 2013956
N-methyl-D-Aspartate Receptor Antibody, IgG, Serum with Reflex to Titer 2004221
Glutamic Acid Decarboxylase Antibody 2001771
Voltage-Gated Potassium Channel (VGKC) Antibody with Reflex to LGI1 and CASPR2 Screen and Titer 2009463
Aquaporin-4 Receptor Antibody by ELISA with Reflex to Aquaporin-4 Antibody, IgG by IFA 2013327
Acetylcholine Receptor Binding Antibody 0080009 (If Acetylcholine Receptor Binding Antibody result is greater than 0.4 nmol/L then Acetylcholine Receptor Modulating Antibody will be added)
Voltage-Gated Calcium Channel (VGCC) Antibody 0092628
Striated Muscle Antibodies, IgG with Reflex to Titer 0050746
Titin Antibody 2005636