Inflammation is rarely one-dimensional, and neither are the biomarkers used to assess it. At Motol University Hospital in Prague, circulating calprotectin has become an important addition to the diagnostic toolbox.
In this interview, Assoc. prof. Tomáš Milota, Ph.D., clinical immunologist and Head of the Department of Immunology, discusses how circulating calprotectin supports differential diagnosis, early decision-making and assessment of disease activity across both adult and paediatric care. With Gentian's calprotectin assay, GCAL®, implemented on a routine chemistry platform, calprotectin is available 24/7 as a rapid STAT parameter, supporting timely and integrated clinical decision-making across departments.
Motol University Hospital (Fakultní nemocnice Motol) is the largest medical facility in the Czech Republic and one of the biggest hospitals in Europe, located in the Motol district of Prague. It provides basic and highly specialised healthcare for patients of all ages, through both outpatient and inpatient services.
The hospital treats millions of patients annually, with over 70,000 inpatients and more than 800,000 outpatient visits each year. It employs around 6,500 of healthcare professionals across a wide range of departments and specialties.
Motol University Hospital, Prague. Image courtesy of Motol University Hospital
Motol University Hospital also serves as a major teaching and research base, particularly for medical students from the Second Faculty of Medicine of Charles University, combining high-quality patient care with education and innovation in medicine.
Tomáš Milota is a healthcare professional specialising in medical diagnostics and laboratory technologies. His career has been focused on the implementation, support, and optimisation of diagnostic systems, with particular attention to quality assurance and clinical reliability.
He has extensive experience working with healthcare institutions, supporting laboratory workflows, and resolving technical and analytical challenges in clinical environments. His expertise bridges medical practice and technological solutions, ensuring effective communication between manufacturers, laboratories, and healthcare providers.
Tomáš is dedicated to improving diagnostic accuracy, operational efficiency, and long-term cooperation within the healthcare sector.
He serves on the governing board of the Czech Society of Allergology and Clinical Immunology (ČSAKI) and is listed as a elected board member of the Czech Immunological Society.
In this interview, Assoc. Prof. Tomáš Milota, Ph.D, shares his experience with implementing and using GCAL® calprotectin in routine care. He discusses how the assay and the biomarker supports laboratory workflows, complements traditional inflammatory markers, and contributes to clinical decision-making across multiple specialties in both adult and paediatric settings.
Calprotectin was introduced into the routine laboratory practice in 2021, offered 5 days a week.
Now, GCAL® is available as STAT parameter 24/7 through the Immunology Laboratory.
Motol Hospital made an important shift, removing POC platforms from departments and have a 24/7 biochemistry and 24/7 immunology lab offering very fast results to all departments with a wide portfolio of available markers.
The CLIA instruments are specifically used for autoimmunity, but not for acute parameters. Switching calprotectin to the chemistry instrument using GCAL® allows to batch acute markers together. This way we can offer calprotectin to all departments both acute and non-acute settings 24/7 as STAT instead of daytime only.
It is important for the clinician to get calprotectin results together with all other standard biomarkers to use it in routine care.
Also, the batching of several crucial parameters into one sample is especially important for children to reduce required sample volume and the clinical chemistry instrument can be easily adapted to smaller volumes.
We are very happy with the set-up and performance of the assay. We have tested the correlation between turbidimetric and chemiluminescence and results were quite nice with a linear correlation.
We have demand across several departments both adult and paediatrics. Infectious diseases and internal and acute medicine, immunology and rheumatology, as well as gastroenterology.
I started to use calprotectin as alternative marker for CRP in chronic patients where CRP did not reliably detect ongoing inflammation. Not replacing, but as alternative for CRP.
Most important are CRP negative patients. That can be seronegative rheumatoid arthritis patients who often also have negative CRP, or patients under biological treatment influencing CRP.
Anti-IL-6 treatments are very important therapy, not only for rheumatoid arthritis, but for other inflammatory disease like Still's disease. In these patients’ calprotectin is a crucial marker for an objective readout of disease activity.
Also, calprotectin is important to reveal the residual activity, because it is sensitive enough to detect the disease activity despite of negative CRP.
This is both relevant to adult and paediatric rheumatology.
Then we have to use clinical signs and we have to look at the alternative markers for information. Calprotectin is one of those markers, because the strategy for alternative markers is to use IL-6 independent markers.
Unfortunately, many composite indexes that are used for disease activity assessment in rheumatology include CRP, like DAS28 and SDAI. I hope that in the future we will have the composite indexes using calprotectin.
Acute-phase markers, like CRP, ESR and ferritin, are secondary markers produced by the liver, in contrast to IL-6 or calprotectin that are directly produced by the immune cells. Calprotectin is a more direct marker of inflammation.
Ultrasonography is very important, but there is one important obstacle: it is not objective. You have to have an experienced physician, so it can be less available for younger physicians. And in addition, it is more time consuming and not available at every visit or office.
‘’I think we should use all the tools we have. Combining examination, scores
and selected biomarkers like calprotectin.’’
Assoc. prof. Tomáš Milota, Ph.D.
Head of Immunology Department, Motol University Hospital, Prague
It's a good question, but it's not so easy to generalise. The physical examinations are very important, but it's the same limitation as ultrasonography, it is objective.
Clinical signs can also be more subtle and have delayed response. With objective and sensitive biomarkers, treatment can be adjusted at early time points avoiding prolonged or delayed treatment.
Also, if you have confirmed diagnosis of rheumatoid arthritis, you might just take the account of swollen joints. But in the first phase, at the beginning, swollen joints can have a wide spectrum of aetiology.
Yes, I think calprotectin can be very important in differential diagnosis.
Joint swelling and inflammation-like symptoms can be also present in accelerated osteoarthrosis. And here, you have to distinguish between inflammatory diseases and non-inflammatory diseases. And really the differential diagnosis with osteoarthritis can be very difficult. It really sounds like absolutely different disease, but in the accelerated phase, it's very, very similar.
There are two big groups of patients with rheumatoid arthritis, seronegative and seropositive. And especially seronegative patients, they are very often CRP negative or with low CRP.
I think there are two approaches. We have to check other autoantibodies, not only rheumatic factor or circulating proteins, but we can check the carbamylated autoantibodies against carbamylated proteins or other autoantibodies. But there is a problem that these alternative autoantibodies are not involved in classification or diagnostic criteria. So, I think we should check alternative biomarkers including calprotectin. One important question regarding the seronegative rheumatoid arthritis is: Is it really rheumatoid arthritis? In differential diagnosis it could be accelerated osteoarthritis as well. Calprotectin can help to differentiate these two.
I had a relatively high number of patients treated with triple therapy, methotrexate, leflunomide, and sulfasalazine, with no effect on disease activity. And these patients were referred as having rheumatoid arthritis. And they were treated for many years. And then we performed x-ray, which just revealed the osteoarthritis. No signs of rheumatoid arthritis. So, they were treated inappropriately. And it's not the failure of the physicians, because once the definitive diagnosis is made, so it's very difficult to change.
‘’We can use calprotectin across the whole disease course, from differential diagnosis to sensitive detection of disease activity under treatment and remission.’’
Assoc. prof. Tomáš Milota, Ph.D.
Head of Immunology Department, Motol University Hospital, Prague
Yes indeed, in both internal and emergency medicine differential diagnosis is very important.
We are offering a panel combining IL-6, CRP, PCT and calprotectin. This spectrum of complementary markers can cover different dynamics because IL-6 is relatively every stage marker of inflammation but with lower stability and half-life. Then you have calprotectin, as early but more stable, PCT and then CRP is relatively late marker. In addition, we offer MXA for differential diagnosis of viral infections.
‘’ A panel of biomarkers really reflects the clinical situation. We'll never have one universal biomarker, but it's about the combination and the timing.’’
Assoc. prof. Tomáš Milota, Ph.D.
Head of Immunology Department, Motol University Hospital, Prague
No, this is also very important for children. In infants and neonates, the very problematic phase is relatively early where you can have relatively low, already decreasing levels of IL-6 and not increasing levels of CRP or PCT. And calprotectin, in my opinion, can cover this gap.
Also, in children we have very limited volume of the blood that can be taken from the patients, so using a panel to cover all complementary markers at once makes it suitable for children and neonates.
If we are talking about the emergency department, it's the time of the first contact with the patient.
There are always the same questions: to use antibiotics or not and to admit patients to the hospital or not. So, we need to have the tools that can provide the answers.
For calprotectin, the most important thing is the dynamics and the predictive value to distinguish between severe and non-severe patients. I think it's the dream of the physician to know it at the time of the first contact with the patient if they can stay calm and to just watch and wait the patients or to admit the patients to the hospital or ICU.
My research project focuses on one specific patient group: Common variable immune deficiency (CVID). The disease is characterised by increased susceptibility to infections and immune system dysregulation associated with autoimmune phenomena. Anti-IL-6 autoantibodies is one part of this story that is very important for me and where I see the future for calprotectin. Here, the episodes of infections may not be reflected by elevation of CRP. This is a very huge field where we can use calprotectin.
Anti-IL-6 autoantibodies are also the link to rheumatology, since the production of anti-IL-6 autoantibodies, is a regulatory mechanism and these autoantibodies can be detected in chronic inflammation, and this is a huge spectrum of diseases. The same effect can be observed in the use of IL-6 inhibitors (such as sarilumab or tocilizumab). Even in case of the severe infectious complications, many of these patients do not have increased CRP.
In these patients with this chronic condition, we would like to use a whole panel: IL-6, CRP, ferritin, serum amyloid and calprotectin.
Gentian GCAL® Calprotectin Immunoassay is the first turbidimetric assay for the quantitative determination of calprotectin in plasma and serum, intended as an aid in the detection and assessment of inflammation and inflammatory response to infections. The assay can be applied on a wide range of automated clinical chemistry analysers.
As the first turbidimetric assay available since 2019, GCAL® offers distinct advantages:
Advanced technology: PETIA assay on clinical chemistry platforms using avian antibodies, which minimises interference from rheumatoid factor and HAMA antibodiesInterested in implementing GCAL® in your laboratory or clinical setting? Share your details and we will contact you to discuss next steps.
* GCAL® is CE-marked under the In Vitro Diagnostic Regulation (IVDR 2017/746, CE 0123). It is not cleared by the U.S. FDA and is not available for sale in the United States.
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