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Article ; Online: Immune Monitoring upon Treatment with Biologics in Sjögren's Syndrome: The What, Where, When, and How.

van Beers, Joyce J B C / Damoiseaux, Jan G M C

2021 Volume 11, Issue 1

Abstract: Over the years, a wide variety of therapeutic antibodies has been successfully introduced in the auto-immunology clinic, and many more are on the way. Many of these treatments address either a pathogenic circulating molecule or a cell-bound molecule. ... ...

Abstract	Over the years, a wide variety of therapeutic antibodies has been successfully introduced in the auto-immunology clinic, and many more are on the way. Many of these treatments address either a pathogenic circulating molecule or a cell-bound molecule. Whereas addressing the former target results in neutralization of the soluble factor and binding to the latter target either inhibits cellular function or induces selective cell death. If this targeted molecule or cell is part of the immune system, this therapy evokes a state of immunodeficiency with infections as a possible consequence. Therefore, immune monitoring is needed to prevent such adverse side effects of immunotherapy. In this paper, different immunotherapies used in Sjögren's syndrome, as well as different approaches to monitoring the immune system, are discussed.
MeSH term(s)	Animals ; Biological Products/pharmacology ; Biological Products/therapeutic use ; Humans ; Models, Biological ; Monitoring, Immunologic ; Sjogren's Syndrome/drug therapy ; Sjogren's Syndrome/immunology
Chemical Substances	Biological Products
Language	English
Publishing date	2021-01-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom11010116
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Article ; Online: Treatment of Autoimmune Diseases with Therapeutic Antibodies: Lessons Learned from PID Patients Allow for Stratification of the Infection Risk.

van Beers, Joyce J B C / Damoiseaux, Jan G M C

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2313, Page(s) 27–44

Abstract: Over the years, a wide variety of therapeutic antibodies has been successfully introduced in the autoimmunology clinic and many more are on the edge to follow. Many of these treatments address either a pathogenic circulating molecule or a cell-bound ... ...

Abstract	Over the years, a wide variety of therapeutic antibodies has been successfully introduced in the autoimmunology clinic and many more are on the edge to follow. Many of these treatments address either a pathogenic circulating molecule or a cell-bound molecule. Whereas the former target results in neutralization of the soluble factor, the latter target either inhibits cellular function or induces selective cell death. If this targeted molecule or cell is part of the immune system, this therapy evokes a state of immunodeficiency. Knowing the exact function of the respective components enables the risk stratification for possible infectious complications in patients treated with biologics. Much of the understanding of the function of immune cells and their associated molecules, in relation to redundancy in the immune system, is derived from studies in knockout mice. However, as mice are not men in terms of their life-expectancy, their infection exposure, or the composition of their immune system, the most useful knowledge for estimating the consequence of therapeutic intervention on immune competence comes from monitoring patients. In the current chapter, we focus on patients with a primary immunodeficiency (PID) because they provide us with a unique perspective to estimate the redundancy of a certain genetic defect for overall immune competence. These patients have inborn errors of the immune system that, in general, are due to single gene defects. Depending on the immunological pathway that is defective, patients can present with different types of (opportunistic) infectious diseases, as well as other clinical manifestations. Based on selected examples, we focus in this chapter on finding parallels in the infectious risk of autoimmune patients treated with biologics and PID patients with a defect in the immunological pathway that is affected by the respective biologic. The goal is to learn from the (dis)similarities between both patient populations in terms of safety profiles of biologic treatments.
MeSH term(s)	Animals ; Autoimmune Diseases/therapy ; Biological Products ; Disease Susceptibility ; Humans ; Immunologic Deficiency Syndromes/therapy ; Infections ; Mice
Chemical Substances	Biological Products
Language	English
Publishing date	2021-09-03
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1450-1_2
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Article ; Online: Lessons learned from the diagnostic work-up of a patient with the bare lymphocyte syndrome type II.

Damoiseaux, Maurits / Damoiseaux, Jan / Pico-Knijnenburg, Ingrid / van der Burg, Mirjam / Bredius, Robbert / van Well, Gijs

Clinical immunology (Orlando, Fla.)

2022 Volume 235, Page(s) 108932

Abstract: A patient presented severe combined immunodeficiency (SCID)-like symptoms. The presence of a substantial number of ... ...

Abstract	A patient presented severe combined immunodeficiency (SCID)-like symptoms. The presence of a substantial number of CD4
MeSH term(s)	Alemtuzumab/therapeutic use ; Antilymphocyte Serum/therapeutic use ; Antineoplastic Agents, Immunological/therapeutic use ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Infant ; Male ; Severe Combined Immunodeficiency/diagnosis ; Severe Combined Immunodeficiency/genetics
Chemical Substances	Antilymphocyte Serum ; Antineoplastic Agents, Immunological ; Immunoglobulins, Intravenous ; Alemtuzumab (3A189DH42V)
Language	English
Publishing date	2022-01-19
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2022.108932
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Article: The Role of Autoantibodies in the Diagnosis of Autoimmune Liver Disease: Lessons Learned from Clinical Practice.

van Beers, Joyce J B C / Koek, Ger H / Damoiseaux, Jan G M C

The journal of applied laboratory medicine

2022 Volume 7, Issue 1, Page(s) 259–267

Abstract: Background: Primary biliary cholangitis (PBC), autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are autoimmune liver diseases associated with distinct autoantibodies. Diagnosis is based upon clinical, serological, and histopathology ... ...

Abstract	Background: Primary biliary cholangitis (PBC), autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are autoimmune liver diseases associated with distinct autoantibodies. Diagnosis is based upon clinical, serological, and histopathology findings. The role of autoantibodies in the diagnosis of these autoimmune liver diseases, with the focus on PBC and AIH, will be discussed. Content: When AIH or PBC is suspected, testing for multiple autoantibodies can be requested. In this mini-review, the different ways in which autoantibodies can be tested (indirect immunofluorescence and antigen-specific tests) in the context of PBC and AIH are discussed, as well as the pitfalls in interpreting the test results. Summary: For appropriate interpretation of test results, an important prerequisite is that the doctor knows which test is used in the laboratory of choice and that the laboratory specialist is aware of what the doctor wants to test for. Good communication between clinician and laboratory specialist can, therefore, aid in the diagnosis of autoimmune liver diseases.
MeSH term(s)	Autoantibodies ; Cholangitis, Sclerosing/diagnosis ; Hepatitis, Autoimmune/diagnosis ; Humans ; Liver Cirrhosis, Biliary/diagnosis ; Liver Diseases/diagnosis
Chemical Substances	Autoantibodies
Language	English
Publishing date	2022-01-05
Publishing country	England
Document type	Journal Article ; Review
ISSN	2576-9456
ISSN	2576-9456
DOI	10.1093/jalm/jfab099
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Article ; Online: Een acuut loopoor.

Hullegie, Saskia / Schilder, Anne G M / Damoiseaux, Roger A M J / Venekamp, Roderick P

Nederlands tijdschrift voor geneeskunde

2022 Volume 166

Abstract: It is often thought that acute ear discharge as a presenting symptom of acute otitis media (AOM) means that the infection is petering out. However, children with AOM presenting with ear discharge due to a spontaneous perforation of the eardrum (AOMd) ... ...

Title translation	Acute ear discharge, a reason for consultation.
Abstract	It is often thought that acute ear discharge as a presenting symptom of acute otitis media (AOM) means that the infection is petering out. However, children with AOM presenting with ear discharge due to a spontaneous perforation of the eardrum (AOMd) have a poorer prognosis (i.e. higher rates of ear pain and/or fever at 3-7 days) than those without ear discharge. In this article we emphasize the importance of physical examination and early treatment of children and adults who present with acute ear discharge.
MeSH term(s)	Adult ; Child ; Humans ; Infant ; Acute Disease ; Anti-Bacterial Agents/therapeutic use ; Otitis Media/complications ; Otitis Media/diagnosis ; Otitis Media/drug therapy ; Pain/drug therapy ; Referral and Consultation
Chemical Substances	Anti-Bacterial Agents
Language	Dutch
Publishing date	2022-08-30
Publishing country	Netherlands
Document type	English Abstract ; Journal Article
ZDB-ID	82073-8
ISSN	1876-8784 ; 0028-2162
ISSN (online)	1876-8784
ISSN	0028-2162
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Article ; Online: B-Cell Analysis for Monitoring Patients Undergoing B-Cell Depletion for the Treatment of Autoimmune Diseases.

Damoiseaux, Jan G M C / van Beers, Joyce J B C / Busch, Matthias / van Paassen, Pieter

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2313, Page(s) 45–55

Abstract: B-cell depleting therapy is increasingly used in the treatment of many distinct autoimmune diseases. This not only involves remission induction therapy, but also maintenance therapy. In this respect, it is of importance to monitor composition of the B- ... ...

Abstract	B-cell depleting therapy is increasingly used in the treatment of many distinct autoimmune diseases. This not only involves remission induction therapy, but also maintenance therapy. In this respect, it is of importance to monitor composition of the B-cell compartment in the peripheral blood. This can be performed at the time of initiation of the therapy, especially in those cases in which the expected clinical effect is not achieved. If B-cells are absent, B-cell depletion may not be the best treatment option; if B-cells are present, the efficacy may be hampered by neutralizing antibodies. For monitoring B-cell recovery it is important not to just enumerate B-cells, but to also phenotype the B-cells. A phenotype of IgD
MeSH term(s)	Antigens, CD ; Antigens, CD20 ; Autoimmune Diseases/therapy ; B-Lymphocytes ; Humans ; Immunoglobulin D
Chemical Substances	Antigens, CD ; Antigens, CD20 ; Immunoglobulin D
Language	English
Publishing date	2021-09-03
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1450-1_3
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Article ; Online: The association between anti-acetylcholine receptor antibody level and clinical improvement in myasthenia gravis.

Marcuse, Florit / Brandts, Lloyd / Moens, Daan / Damoiseaux, Jan / Hochstenbag, Monique / Hoeijmakers, Janneke G J / Maessen, Jos G / De Baets, Marc

European journal of neurology

2022 Volume 29, Issue 4, Page(s) 1187–1197

Abstract: Background and purpose: Anti-acetylcholine receptor (AChR) antibodies (ab) in the serum are detected in most patients with generalized myasthenia gravis (MG) and used as a diagnostic tool. The aim of this study was to analyse a possible association ... ...

Abstract	Background and purpose: Anti-acetylcholine receptor (AChR) antibodies (ab) in the serum are detected in most patients with generalized myasthenia gravis (MG) and used as a diagnostic tool. The aim of this study was to analyse a possible association between anti-AChR-ab serum levels and clinical improvement of MG. Methods: The Maastricht University Medical Center is a centre of expertise for the treatment of MG. Between 1997 and 2020, more than 4000 anti-AChR-ab blood samples were measured for clinical care using a quantitative radioimmunoassay technique. These results, in combination with clinical status obtained from the patients' electronic patient files, were retrospectively analysed by a single blinded clinician. Symptoms of MG were classified using the Myasthenia Gravis Foundation of America (MGFA) scale. Results: In total, 90 anti-AChR-ab-positive MG patients with 837 blood samples were included. The median follow-up time was 72 months. The majority of the included patients were women (61.1%), were on immunosuppressive drug therapy (88.9%), and underwent a thymectomy (54.4%). Multilevel logistic regression analysis showed a significantly inverse association between change in anti-AChR-ab level and the odds of MGFA improvement (per 10% decrease of anti-AChR-ab level: odds ratio 1.21, 95% confidence interval 1.12-1.31; p < 0.001). Conclusions: A change in anti-AChR-ab serum level is associated with clinical status in patients with MG. Analyses of anti-AChR-ab are not only useful for diagnostics but also in follow-up of adult symptomatic patients with MG. The use of repetitive anti-AChR-ab serum levels might be valuable in long-term monitoring for clinical improvement in patients with MG, however, further research is required for specific recommendations.
MeSH term(s)	Adult ; Autoantibodies ; Female ; Humans ; Male ; Myasthenia Gravis ; Receptors, Cholinergic ; Retrospective Studies ; Thymectomy
Chemical Substances	Autoantibodies ; Receptors, Cholinergic
Language	English
Publishing date	2022-01-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1280785-0
ISSN	1468-1331 ; 1351-5101 ; 1471-0552
ISSN (online)	1468-1331
ISSN	1351-5101 ; 1471-0552
DOI	10.1111/ene.15238
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Zs.A 4738: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Favorable long term effects of intensified immunosuppression combined with therapeutic plasma exchange in patients with early-onset progressive systemic sclerosis-related interstitial lung disease.

Potjewijd, J / Tobal, R / Silvertand, D / Gietema, H A / Damoiseaux, J G M C / van Paassen, P

Journal of translational autoimmunity

2022 Volume 5, Page(s) 100174

Abstract: Objective: Systemic sclerosis (SSc) related mortality and morbidity remains high. Immunosuppressive therapy is considered most effective when immune activity and inflammation but not fibrosis still dominates the disease process. This study evaluated ... ...

Abstract	Objective: Systemic sclerosis (SSc) related mortality and morbidity remains high. Immunosuppressive therapy is considered most effective when immune activity and inflammation but not fibrosis still dominates the disease process. This study evaluated long-term intensified immunosuppression combined with therapeutic plasma exchange (TPE) in early-onset progressive SSc-related interstitial lung disease (ILD). Methods: The study cohort consisted of 161 SSc patients, with a median follow-up time of 8.9 years. The standardized mortality rate (SMR) and overall survival was calculated in patients with and without cardiopulmonary involvement. We used a standardized, pragmatic, non-randomized approach to treat 24 consecutive early progressive SSc-ILD patients with intensified immunosuppressive therapy, including plasma exchange. Outcome measurements were event-free survival (EFS), pulmonary function and safety profile. The outcome was compared with the analyzed data from the other SSc-ILD patients, who did not fulfill the inclusion criteria, and instead were treated with estimated optimal care (EOc). Results: The age-adjusted SMR of all 161 SSc patients was 3.0 (CI95%; 0.32-5.68). EFS at 10 years was 49.9% in the intensified treatment group and 43.3% in the EOc group (p = 0.106). Improvement of the percentage of predicted forced vital capacity (%pFVC) and percentage of predicted diffusing capacity for carbon monoxide (%pDLco) in the intensified treatment group was +10.1% respectively +3.6%, compared to a decrease of respectively 10.8% and 7% in the EOc (p < 0.001 resp. p = 0.019). Safety analysis showed 1 death (female patient, over 75 years of age), due to pneumosepsis, in the intensified treatment group. Conclusion: Intensified and long-lasting immunosuppression combined with TPE is safe in early severe systemic sclerosis and is associated with improved EFS and pulmonary function as compared to the outcome in the variable but EOc group. Our findings warrant larger studies for confirmation.
Language	English
Publishing date	2022-11-21
Publishing country	Netherlands
Document type	Journal Article
ISSN	2589-9090
ISSN (online)	2589-9090
DOI	10.1016/j.jtauto.2022.100174
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Article ; Online: The intrinsic coagulation pathway plays a dominant role in driving hypercoagulability in ANCA-associated vasculitis.

Busch, Matthias H / Ysermans, Renée / Aendekerk, Joop P / Timmermans, Sjoerd A M E G / Potjewijd, Judith / Damoiseaux, Jan G M C / Spronk, Henri M H / Ten Cate, Hugo / Reutelingsperger, Chris P / Nagy, Magdolna / van Paassen, Pieter

Blood advances

2024 Volume 8, Issue 5, Page(s) 1295–1304

Abstract: Abstract: The risk of a venous thrombotic event (VTE) is increased in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV); however, a detailed understanding of the underlying mechanisms of hypercoagulability is limited. ... ...

Abstract	Abstract: The risk of a venous thrombotic event (VTE) is increased in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV); however, a detailed understanding of the underlying mechanisms of hypercoagulability is limited. We assessed prospectively different coagulation parameters in 71 patients with active AAV at baseline and after 6 months of follow-up. D-dimers and fibrinogen were increased in most patients at presentation and remained elevated in half of the patients. Particularly, thrombin-antithrombin (T:AT) complex and activated coagulation factors in complex with their natural inhibitors of the intrinsic coagulation pathway (ie, activated FXII:C1 esterase inhibitor [FXIIa:C1Inh], FXIa:AT, and FXIa:alpha1-antitrypsin [FXIa:α1AT]) were profoundly elevated in patients at baseline. Thrombin formation was dominantly correlated with coagulation factors of the intrinsic pathway (ie, FXIIa:AT, FXIa:AT, FXIa:α1AT, and FXIa:C1Inh) compared to the extrinsic pathway (ie, FVIIa:AT). Hypercoagulability correlated with higher disease activity, ANCA levels, C-reactive protein, serum creatinine, and proteinuria. VTEs were observed in 5 out of 71 (7%) patients within 1 month (interquartile range, 1-5) after inclusion. Baseline T:AT levels were significantly higher in patients with VTE than in those without VTE (P = .044), but other clinical or laboratory markers were comparable between both groups. Hypercoagulability is dominantly characterized by activation of the intrinsic coagulation pathway and elevated D-dimers in active AAV. The driving factors of hypercoagulability are yet to be studied but are most likely related to an interplay of increased disease activity, vascular inflammation, and endothelial damage. Future targets for intervention could include inhibitors of the intrinsic coagulation pathway and compounds specifically reducing the hyperinflammatory state.
MeSH term(s)	Humans ; Antibodies, Antineutrophil Cytoplasmic ; Thrombin ; Blood Coagulation ; Thrombophilia/etiology ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2024-01-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023011937
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Article ; Online: Semi-physiological Enriched Population Pharmacokinetic Modelling to Predict the Effects of Pregnancy on the Pharmacokinetics of Cytotoxic Drugs.

Janssen, J M / Damoiseaux, D / van Hasselt, J G C / Amant, F C H / van Calsteren, K / Beijnen, J H / Huitema, A D R / Dorlo, T P C

Clinical pharmacokinetics

2023 Volume 62, Issue 8, Page(s) 1157–1167

Abstract: Background and objective: As a result of changes in physiology during pregnancy, the pharmacokinetics (PK) of drugs can be altered. It is unclear whether under- or overexposure occurs in pregnant cancer patients and thus also whether adjustments in ... ...

Abstract	Background and objective: As a result of changes in physiology during pregnancy, the pharmacokinetics (PK) of drugs can be altered. It is unclear whether under- or overexposure occurs in pregnant cancer patients and thus also whether adjustments in dosing regimens are required. Given the severity of the malignant disease and the potentially high impact on both the mother and child, there is a high unmet medical need for adequate and tolerable treatment of this patient population. We aimed to develop and evaluate a semi-physiological enriched model that incorporates physiological changes during pregnancy into available population PK models developed from non-pregnant patient data. Methods: Gestational changes in plasma protein levels, renal function, hepatic function, plasma volume, extracellular water and total body water were implemented in existing empirical PK models for docetaxel, paclitaxel, epirubicin and doxorubicin. These models were used to predict PK profiles for pregnant patients, which were compared with observed data obtained from pregnant patients. Results: The observed PK profiles were well described by the model. For docetaxel, paclitaxel and doxorubicin, an overprediction of the lower concentrations was observed, most likely as a result of a lack of data on the gestational changes in metabolizing enzymes. For paclitaxel, epirubicin and doxorubicin, the semi-physiological enriched model performed better in predicting PK in pregnant patients compared with a model that was not adjusted for pregnancy-induced changes. Conclusion: By incorporating gestational changes into existing population pharmacokinetic models, it is possible to adequately predict plasma concentrations of drugs in pregnant patients which may inform dose adjustments in this population.
MeSH term(s)	Pregnancy ; Child ; Female ; Humans ; Docetaxel/therapeutic use ; Epirubicin/pharmacokinetics ; Epirubicin/therapeutic use ; Models, Biological ; Antineoplastic Agents/pharmacokinetics ; Paclitaxel/pharmacokinetics ; Doxorubicin ; Neoplasms/drug therapy
Chemical Substances	Docetaxel (15H5577CQD) ; Epirubicin (3Z8479ZZ5X) ; Antineoplastic Agents ; Paclitaxel (P88XT4IS4D) ; Doxorubicin (80168379AG)
Language	English
Publishing date	2023-06-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197627-8
ISSN	1179-1926 ; 0312-5963
ISSN (online)	1179-1926
ISSN	0312-5963
DOI	10.1007/s40262-023-01263-1
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