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Category: Autoimmune

Autoimmune thyroid diseases affect millions of people worldwide and are among the most frequently diagnosed autoimmune disorders. As the demand for accurate thyroid diagnostics continues to grow, so too does the need for high-quality quality control (QC) and calibrator materials that ensure reliable test performance. While much attention is given to developing sensitive and specific anti-thyroid peroxidase (anti-TPO) assays, an equally important challenge is the sourcing of biological materials that enable the manufacture of consistent, clinically relevant quality control materials.

 

For manufacturers of QC materials and calibrators, selecting the right anti-TPO material is also critical to achieving reliable lot-to-lot performance, maintaining long-term supply and supporting confidence in diagnostic testing.

 

Why Anti-TPO Testing Matters

Anti-thyroid peroxidase (anti-TPO) antibodies are recognised as one of the most important biomarkers for autoimmune thyroid disease. They are routinely measured to aid the diagnosis and monitoring of conditions including:

  • Hashimoto’s thyroiditis
  • Graves’ disease
  • Postpartum thyroiditis

In many patients, anti-TPO antibodies are present long before clinical symptoms appear, making them an important marker for early disease detection and ongoing patient management.

 

Increasing Anti-TPO testing demand

The demand for anti-TPO tests is steadily increasing. This growth is driven by the rising prevalence of autoimmune thyroid diseases and an overall shift toward preventive healthcare.

  • Rising Autoimmune Cases

The global anti-TPO testing market is growing at a compound annual growth rate of roughly 7.2%, with an aging population disproportionately affected by thyroid dysfunctions.1

  • Routine Screening

Widespread routine screening and initiatives to catch thyroid issues early are significantly boosting testing volumes.2

  • Pregnancy Monitoring

US guidelines recommend checking anti-TPO levels in pregnant women to assess the risk of postpartum thyroiditis and miscarriage. 3

 

The Challenge Doesn’t End When the Assay Is Commercialised

Once an anti-TPO assay has been validated and commercialised, manufacturers of quality control materials face a different challenge, to manufacture quality controls that perform consistently over many production lots while behaving as closely as possible to authentic patient samples.

Achieving this requires biological materials that offer both clinical relevance and dependable supply, something that is becoming increasingly difficult as demand for autoimmune thyroid testing continues to grow.

 

Why Native Anti-TPO Materials Are Difficult to Source

Although autoimmune thyroid disease is common, sourcing suitable anti-TPO-positive biospecimens for quality control manufacturing presents several challenges.

  • High-Titre Donors Are Limited

Only a proportion of patients produce antibody levels suitable for QC manufacturing. Improved patient management guidelines and targeted therapies mean conditions like Hashimoto’s thyroiditis are being caught and managed much earlier. Early treatment and supplementation protocols (such as selenium and vitamin D) can successfully suppress and lower these antibody levels over time. As a result, fewer patients maintain the exceptionally high, raw, untreated titres that were historically more common. 4 As a result, finding donors with sufficiently high anti-TPO concentrations can be a challenge.

  • Natural Biological Variation

Every patient sample is different. Anti-TPO antibody concentrations and biological characteristics vary naturally, making it challenging to achieve consistent manufacturing lots using donor-derived material.

  • Supply

Native disease-state biospecimens rely entirely on donor availability. Securing sufficient volumes of well-characterised material to support long-term commercial manufacturing programmes requires extensive collection networks and careful planning.

 

Native Biospecimens Remain the Gold Standard

Despite these challenges, native anti-TPO-positive serum and plasma remain the benchmark for clinically relevant quality control materials.

Because they contain naturally occurring human antibodies within their original biological matrix, native biospecimens closely resemble the samples analysed in clinical laboratories every day. This helps manufacturers produce quality controls that reflect real-world assay performance, perform reliably across a range of diagnostic platforms and maintain confidence in patient testing.

For this reason, native anti-TPO biospecimens continue to play an essential role in establishing clinically representative quality control materials.

 

Human Fc TPO Antibodies: Supporting Long-Term Manufacturing

Engineered Human Fc anti-TPO antibodies provide an alternative solution by offering reproducible antibody performance with a sustainable manufacturing supply.

Whilst some recombinant antibodies lack key post-translational modifications or fail to achieve the complex folding of native immunoglobulins, engineered Human Fc antibodies achieve both enabling performance that closely reflects native disease-state material. While conventional single monoclonal antibodies may not fully reproduce the heterogeneous characteristics of native polyclonal patient samples, carefully selected Human Fc antibodies can demonstrate highly native-like analytical performance, including excellent assay reactivity and linearity where validated.

For quality control manufacturers, Human Fc antibodies can provide:

  • Excellent lot-to-lot consistency
  • Reliable long-term supply
  • Reduced dependence on scarce donor material
  • Greater manufacturing scalability
  • Improved production planning and supply continuity

 

Native Biospecimens vs Human Fc Antibodies

 

Native Anti-TPO Biospecimens Human Fc Antibodies
Clinical relevance Excellent: derived from real patient samples Designed to closely replicate target antibody characteristics
Biological matrix Natural human serum or plasma Can be incorporated into defined matrices
Lot-to-lot consistency Can vary between donor collections Highly reproducible between manufacturing batches
Long-term supply Dependent on donor availability Sustainable and scalable manufacturing
Scalability Limited by clinical collections Suitable for large-scale production

 

Conclusion

The demand for autoimmune thyroid testing continues to increase, placing greater emphasis on the quality, consistency and sustainability of the biological materials used in quality control manufacturing.

Logical Biological offers reliable access to native anti-TPO-positive serum and plasma, and engineered Human Fc anti-TPO IgG antibodies, giving QC manufacturers greater flexibility to select the material best suited to their performance, consistency and supply requirements.

 

References:

  1. Data Insights Report: Anti Thyroid Peroxidase Antibody Testing Market. datainsightsreports.com/reports/anti-thyroid-peroxidase-antibody-testing-market-202227
  2. Fortune Business Insights Report: Thyroid Function Test Market Size, Share and Analysis by Type. fortunebusinessinsights.com/industry-reports/thyroid-function-test-market-101037
  3. Mayo Clinic Overview: Thyroid peroxidase antibody test: What is it? mayoclinic.org/diseases-conditions/hashimotos-disease/expert-answers/thyroid-disease/faq-20058114
  4. T Siriwardhane et al. Significance of Anti-TPO as an Early Predictive Marker in Thyroid Disease. Autoimmune Dis. Jul 28;2019:1684074. doi.org/10.1155/2019/1684074

Blog Overview

October 7th 2026
Autoimmune Quality Controls Thyroid
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Autoimmune diabetes is often misunderstood, misdiagnosed, or detected later than it should be. The key to identifying it early lies in specific autoimmune markers, particularly anti-Glutamate Decarboxylase (GAD), anti-Protein Tyrosine Phosphatase-like Protein IA-2 (IA-2), anti-Zinc transporter 8 (ZnT8), and anti-insulin autoantibody (IAA). These lab tests help doctors determine whether high blood sugar is caused by immune destruction of pancreatic beta cells rather than insulin resistance alone.

 

What Is Autoimmune Diabetes?

Autoimmune diabetes occurs when the immune system mistakenly attacks insulin-producing beta cells in the pancreas. This process underlies:

  • Type 1 diabetes
  • LADA (Latent Autoimmune Diabetes in Adults),  a slower, adult-onset form, often misdiagnosed as Type 2 Diabetes because, for a period, these patients still produce insulin but at an insufficient level.

Unlike Type 2 diabetes, the root issue is loss of insulin production, not just insulin resistance.

 

Autoimmune Diabetes is increasing and often misunderstood

Some statistics:

  • Prevalence of Type 1 diabetes varies globally from 3.5:10,000 in Africa to 12.2:10,000 in the USA and is increasing at an estimated 3–4% per year in Europe.1
  • The prevalence of LADA in a population of Type 2 Diabetes Mellitus patients is between 4% and 12%.2

Delayed diagnosis of Autoimmune Diabetes allows blood sugar levels to remain high, which can lead to severe, life-threatening complications, most notably Diabetic Ketoacidosis (DKA). A delayed LADA diagnosis often means the patient is wrongly treated for Type 2 diabetes, failing to receive essential insulin. Detecting this difference early changes treatment decisions and long-term outcomes.

As LADA can easily be confused with Type 2 Diabetes Mellitus, and it’s essential to diagnose autoimmune diabetes as early as possible, is there a case for increased testing of a panel of autoimmune markers?

 

Immunologic Targets Driving Assay Development

Anti-Glutamate Decarboxylase (GAD), anti-Protein Tyrosine Phosphatase-like Protein IA-2 (IA-2), anti-Zinc transporter 8 (ZnT8), and anti-insulin autoantibody (IAA) are all proteins produced as a result of immune dysregulation that target pancreatic beta cells. They have different modes of action and value as diagnostic markers.

Doctors should consider these tests when a diabetes diagnosis is unclear. These tests can help confirm Type 1 diabetes or LADA. A LADA diagnosis should be considered if a patient is not overweight, has a personal/family history of autoimmune diseases, and shows a rapid decline in glycaemic control despite following a type 2 diabetes management plan. They are often positive for GAD and ZnT8.

 

Glutamate Decarboxylase (GAD/ GAD65) Antibodies

This is the highest prevalence autoantibody in autoimmune diabetes. These antibodies target the glutamic acid decarboxylase enzyme, triggering an immune response that destroys insulin-producing pancreatic beta cells. Here are some features that make it an interesting marker:

  • Dominant marker in adult-onset autoimmune diabetes (LADA).
  • It can remain detectable for years making it ideal for retrospective and longitudinal studies.
  • There is strong evidence of immune-mediated diabetes, essential for screening assays and multiplex panels.

 

IA-2 Autoantibodies

Associated with active beta-cell destruction by targeting a beta-cell protein involved in insulin secretion, this marker appears closer to disease onset and correlates with faster progression to insulin dependence.

  • IA-2 autoantibodies would be crucial in a panel that was looking to predict the transition to insulin dependence.

 

Insulin Autoantibodies (IAA)

Often the first antibody detected, especially in paediatric cases, IAA binds to insulin, forming immune complexes that cause erratic blood sugar levels. It is a useful marker because:

  • It helps identify early autoimmune diabetes, so is key for developing early-disease detection assays.
  • Important in neonatal/early-onset cohorts.

It is important to note that post-exogenous insulin exposure confounds measurements, so it is most informative and best measured before insulin therapy starts.

 

Zinc transporter 8 (ZnT8 / a-zinc) Autoantibodies

ZnT8 autoantibodies target the ZnT8 protein located on the membrane of insulin secretory granules in beta cells. By destroying the beta cells, anti-ZnT8 causes a decline in insulin secretion.

  • It improves detection when GAD/IA-2 are negative, increasing overall diagnostic sensitivity, making it useful for uncovering “seronegative” autoimmune cases that may otherwise be missed. When the ZnT8 antibody is tested along with the 3 other T1DM autoantibodies, autoimmunity detection rates were up to 98% in new-onset T1DM cases.3

 

Why Test Multiple Antibodies?

Result Meaning
1 antibody positive Autoimmune diabetes possible
2+ antibodies positive Strong evidence of autoimmune diabetes
Different antibody patterns Help estimate stage & speed of progression

As each marker appears at a different stage of disease, testing multiple markers and combining the data improves the accuracy of the diagnosis and provides doctors with valuable information to guide treatment decisions and insulin timing.

 

Important Companion Tests

Marker Application
C-peptide Correlates autoantibody status with functional beta-cell loss, measuring how much insulin the body still makes. Low or declining C-peptide is indicative of beta-cell failure, therefore distinguishing Type 1 diabetes/ LADA from Type 2 diabetes. It can help decide when insulin is needed and track disease progression.
HbA1c & glucose Confirm diabetes and severity. Used to monitor diabetes management and glycaemic status.
Islet Cell Antibodies (ICA) An older, indirect test for autoimmune diabetes that is less specific than modern markers discussed earlier in the article. It is sometimes included for completeness.
Proinsulin Elevated levels can indicate Beta-cell stress. Is typically used in research or speciality cases.

 

Is It Time for Broader Access to Autoimmune Diabetes Testing?

Current tests for these more specialised autoimmune markers are often Research Use Only (RUO) and testing is typically performed in large reference labs using validated ELISA/ immunoassay methods.

Early detection has been shown to prevent hospitalisation and life-threatening conditions. Screening for Type 1 Diabetes will help people maximize their opportunities to delay Type 1 Diabetes onset while preparing for diabetes care.4  Understanding these markers transforms how diabetes is classified, monitored, and treated and is especially useful in adults who don’t fit neatly into “Type 1” or “Type 2” diagnostic buckets.

 

References

  1. M Popoviciu et al. Type 1 Diabetes Mellitus and Autoimmune Diseases: A Critical Review of the Association and the Application of Personalized Medicine. J. Pers. Med. 2023, 13(3), 422; https://doi.org/10.3390/jpm13030422
  2. V Rajkumar et al. Latent Autoimmune Diabetes. National Institute of Medicine. March 1, 2024. https://www.ncbi.nlm.nih.gov/books/NBK557897/
  3. Maniattu et al. Latent Autoimmune Diabetes of Adults Due to Positive Zinc Transporter 8 Antibody. Annals of Internal Medicine: Clinical Cases, 2025. Vol 4, Number 6. https://doi.org/10.7326/aimcc.2024.1092
  4. D Moore et al. Recommendations for Screening and Monitoring the Stages of Type 1 Diabetes in the Immune Therapy Era. Int J Gen Med. 2024 Jul 9;17:3003–3014. https://doi.org/10.2147/IJGM.S438009

Blog Overview

April 18th 2026
Autoimmune Diabetes
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As autoimmune thyroid testing grows, QC manufacturers face an increasing challenge to secure anti-TPO materials that combine reliable performance with consistent, long-term supply. Native anti-TPO serum and plasma provide excellent clinical relevance, but high-titre material can be difficult to source. Engineered Human Fc anti-TPO antibodies offer an alternative route to greater consistency and scalable supply.
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What is HAMA?

HAMA is an acronym for Human Anti-Mouse Antibodies. Some humans produce HAMA and have it present in their blood. Unfortunately for them, and the in vitro diagnostics industry, the presence of Human anti-mouse Antibodies (HAMA) in patient samples can lead to false positive and false negative results in immunoassays.


Murine MC HAMA

Why do some Humans produce HAMA?

Some people work directly with mice while others might inadvertently encounter mouse proteins or immunoglobulins by coming into contact with mouse urine or contaminated food. These people could develop an immune response against mouse immunoglobulins (antibodies) they encounter such that their immune system produces HAMA.

In the past, mouse monoclonal antibodies were used as therapeutics and could elicit an immune response resulting in the presence of HAMA in human individuals. However, these days monoclonal antibody-based pharmaceuticals are “humanised” to avoid this problem.

Presence of HAMA in individuals is rare, but still needs to be accounted for in immunoassay design.

Could I interfere with your immunoassay?

How can HAMA impact Immunoassays?

When a patient is tested for a condition, the test performed is commonly an immunoassay and the sample that is tested is serum or plasma derived from the patient’s blood. Immunoassays are typically developed using a “matched pair” of mouse monoclonal antibodies to bind to and detect the marker of interest. The ‘marker’ of interest depends on the condition being diagnosed but could be, for example, Troponin I which is a marker of acute myocardial infarction, or HIV p24 antigen which is a marker for the presence of HIV virus. The patient sample (e.g. serum or plasma) is applied to the immunoassay and if the marker being tested for is present the mouse monoclonal antibodies within the assay bind to it and a signal is generated.

However, where HAMA is present in the patient sample the HAMA can bind to the mouse monoclonal antibodies used as immunoassay components and can either i) block the mouse monoclonal antibodies from binding to the marker of interest resulting in a false negative result, or ii) form a bridge between the pair of mouse monoclonal antibodies, generating false positive signal.  Where a patient receives an incorrect diagnosis due to the presence of HAMA, the consequences can be devastating. At least 34 cases of hCG false-positive tests in the United States between 1999-2004 resulted in the patients receiving chemotherapy or surgery, including 10 hysterectomies, for assumed cancer1.

How can HAMA interference be prevented in immunoassays?

Assay manufacturers can develop their assays in such a way as to minimise the interference from HAMA, for example by adding excess mouse immunoglobulin to their assay buffers. When this is done, the HAMA present in the patient sample can bind the excess mouse immunoglobulin rather than the reagents being used in the assay.

Immunoassay developers will need to access patient material in order to design an assay that is not affected by HAMA, and also to show that the assay works in the presence of HAMA. Logical Biological is able to provide HAMA-positive serum and plasma.

Even if blockers are used to control HAMA, the heterogeneous nature of its presence in patients mean that it is difficult to rule out its influence entirely, unless it is measured. If HAMA is suspected, the clinical laboratory can perform serial dilutions with an appropriate buffer to demonstrate nonparallelism (higher recovery of the signal than expected).

An alternative solution to controlling for HAMA interference is to use monoclonal antibodies from an alternative species in the immunoassay, in place of mouse monoclonal antibodies. Rabbit and Sheep monoclonal antibodies are candidates here. However, this is not a great solution as some individuals in the population will be producing human anti-rabbit and anti-sheep antibodies. Synthetic peptide binders and/or recombinant antibodies can theoretically avoid the problem of HAMA when used as alternatives to antibodies raised in animals.

Reference

  1. Human Chorionic Gonadotropin (hCG), By Laurence A. Cole, Stephen A. Butler. Elsevier. 2010.

Blog Overview

October 17th 2019
Antibodies Autoimmune Immunoassays Interference
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Autoimmune Quality Controls Thyroid

The Hidden Challenge in Autoimmune Thyroid Testing: Choosing the Right Anti-TPO Materials for Quality Control Manufacturing
October 7th 2026
As autoimmune thyroid testing grows, QC manufacturers face an increasing challenge to secure anti-TPO materials that combine reliable performance with consistent, long-term supply. Native anti-TPO serum and plasma provide excellent clinical relevance, but high-titre material can be difficult to source. Engineered Human Fc anti-TPO antibodies offer an alternative route to greater consistency and scalable supply.
Read More
a-TPO IgG Antibodies in blood