4.8 Article

Autoantibodies in Serum of Systemic Scleroderma Patients: Peptide-Based Epitope Mapping Indicates Increased Binding to Cytoplasmic Domains of CXCR3

Journal

FRONTIERS IN IMMUNOLOGY
Volume 9, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.00428

Keywords

autoantibodies; CXCR3; peptide array; systemic sclerosis; G protein-coupled receptor

Categories

Funding

  1. Deutsche Forschungsgemeinschaft Cluster of Excellence Inflammation at Interfaces [306/2]
  2. Research Training Group Grant [1727/1 (TP2)]
  3. [RI 1056 11/1-2]

Ask authors/readers for more resources

Systemic sclerosis (SSc) is a severe chronic autoimmune disease with high morbidity and mortality. Sera of patients with SSc contain a large variety of autoantibody (aab) reactivities. Among these are functionally active aab that bind to G protein-coupled receptors (GPCR) such as C-X-C motif chemokine receptor 3 (CXCR3) and 4 (CXCR4). Aab binding to the N-terminal portion of these two GPCRs have been shown to be associated with slower disease progression in SSc, especially deterioration of lung function. Aabs binding to GPCRs exhibit functional activities by stimulating or inhibiting GPCR signaling. The specific functional activity of aabs crucially depends on the epitopes they bind to. To identify the location of important epitopes on CXCR3 recognized by aabs from SSc patients, we applied an array of 36 overlapping 18-20mer peptides covering the entire CXCR3 sequence, comparing epitope specificity of SSc patient sera (N = 32, with positive reactivity with CXCR3) to healthy controls (N = 30). Binding of SSc patient and control sera to these peptides was determined by ELISA. Using a Bayesian model approach, we found increased binding of SSc patient sera to peptides corresponding to intracellular epitopes within CXCR3, while the binding signal to extracellular portions of CXCR3 was found to be reduced. Experimentally determined epitopes showed a good correspondence to those predicted by the ABCpred tool. To verify these results and to translate them into a novel diagnostic ELISA, we combined the peptides that represent SSc-associated epitopes into a single ELISA and evaluated its potential to discriminate SSc patients (N = 31) from normal healthy controls (N = 47). This ELISA had a sensitivity of 0.61 and a specificity of 0.85. Our data reveals that SSc sera preferentially bind intracellular epitopes of CXCR3, while an extracellular epitope in the N-terminal domain that appears to be target of aabs in healthy individuals is not bound by SSc sera. Based upon our results, we could devise a novel ELISA concept that may be helpful for monitoring of SSc patients.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Dermatology

Isotretinoin and the risk of psychiatric disturbances: A global study shedding new light on a debatable story

Khalaf Kridin, Ralf J. Ludwig

Summary: In this retrospective cohort study, patients with acne treated with isotretinoin had a lower risk of depression compared to those treated with oral antibiotics, but a comparable risk of major depressive disorder. The risk of suicidal attempts was similar between the two groups, but patients under isotretinoin had a higher risk of suicidal ideation. Patients under isotretinoin also had a lower risk of post-traumatic stress disorder, anxiety, bipolar disorder, schizophrenia, and adjustment disorder. The study suggests that isotretinoin may confer a lower risk of several psychiatric comorbidities.

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY (2023)

Letter Dermatology

Mortality in eight autoimmune bullous diseases: A global large-scale retrospective cohort study

Katharina Boch, Henner Zirpel, Diamant Thaci, Noor Mruwat, Detlef Zillikens, Ralf J. Ludwig, Khalaf Kridin

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY (2023)

Review Immunology

Autoimmune pre-disease

Katja Bieber, Jennifer E. Hundt, Xinhua Yu, Marc Ehlers, Frank Petersen, Christian M. Karsten, Jorg Koehl, Khalaf Kridin, Kathrin Kalies, Anika Kasprick, Stephanie Goletz, Jens Y. Humrich, Rudolf A. Manz, Axel Kuenstner, Christoph M. Hammers, Reza Akbarzadeh, Hauke Busch, Christian D. Sadik, Tanja Lange, Hanna Grasshoff, Alexander M. Hackel, Jeanette Erdmann, Inke Koenig, Walter Raasch, Mareike Becker, Anja Kerstein-Staehle, Peter Lamprecht, Gabriela Riemekasten, Enno Schmidt, Ralf J. Ludwig

Summary: Approximately 5% of the world-wide population is affected by autoimmune diseases, which are still difficult to treat and have a significant economic impact. The progression from harmless to inflammatory autoimmune disease conditions is a key factor. Biomarkers that can predict this progression would be highly impactful. Factors such as genetics, environment, and lifestyle choices may influence the progression from benign to inflammatory autoimmune conditions. Research is needed to define and modulate autoimmune predisease.

AUTOIMMUNITY REVIEWS (2023)

Biographical-Item Dermatology

Obituary: Professor Detlef Zillikens, 1958-2022

Christoph M. Hammers

BRITISH JOURNAL OF DERMATOLOGY (2023)

Article Dermatology

Isotretinoin and the risk of inflammatory bowel disease and irritable bowel syndrome: A large-scale global study

Khalaf Kridin, Ralf J. Ludwig

Summary: Isotretinoin does not increase the risk of Crohn's disease, but it may be associated with a slight and temporary increase in the risk of ulcerative colitis. However, it can lower the risk of irritable bowel syndrome.

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY (2023)

Letter Dermatology

The cardiometabolic safety of interleukin 23 versus interleukin 17 inhibitors in psoriasis: A large-scale global cohort study

Khalaf Kridin, Noor Mruwat, Diamant Thaci, Ralf J. Ludwig

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY (2023)

Review Veterinary Sciences

The human skin organ culture model as an optimal complementary tool for murine pemphigus models

Veronika Hartmann, William V. J. Hariton, Siavash Rahimi, Christoph M. Hammers, Ralf J. Ludwig, Eliane J. Mueller, Jennifer E. Hundt

Summary: Pemphigus is a severe autoimmune bullous disease that targets adhesion proteins desmoglein 3 and/or desmoglein 1. Current treatment involves systemic immunosuppression, and drug development focuses on B cells, autoantibodies, and tissue pathology. A human skin organ culture (HSOC) model has been established as an alternative to animal models for studying pemphigus, replicating key features of the disease.

LABORATORY ANIMALS (2023)

Article Dermatology

Association of Rituximab With Risk of Long-term Cardiovascular and Metabolic Outcomes in Patients With Pemphigus

Khalaf Kridin, Noor Mruwat, Ralf J. Ludwig

Summary: Patients with pemphigus who were treated with rituximab had a lower risk of long-term cardiovascular and metabolic outcomes compared with those receiving first-line corticosteroid-sparing agents. Rituximab may be particularly preferred in patients with preexisting cardiovascular and metabolic risk factors.

JAMA DERMATOLOGY (2023)

Article Immunology

Risk factors and sequelae of epidermolysis bullosa acquisita: A propensity-matched global study in 1,344 patients

Khalaf Kridin, Artem Vorobyev, Cristian Papara, David A. De Luca, Katja Bieber, Ralf J. Ludwig

Summary: Identification of risk factors and sequelae of diseases is crucial for primary prevention and disease management. This study used TriNetX to identify risk factors and sequelae of the rare autoimmune disease EBA. The findings revealed chronic inflammatory diseases, especially lupus erythematosus and lichen planus, as the highest risk factors for EBA development and metabolic and cardiovascular diseases, and thrombosis as the most common sequelae after EBA diagnosis.

FRONTIERS IN IMMUNOLOGY (2023)

Article Multidisciplinary Sciences

Impact of diet and host genetics on the murine intestinal mycobiome

Yask Gupta, Anna Lara Ernst, Artem Vorobyev, Foteini Beltsiou, Detlef Zillikens, Katja Bieber, Simone Sanna-Cherchi, Angela M. M. Christiano, Christian d D. Sadik, Ralf j J. Ludwig, Tanya Sezin

Summary: In this study, 591 mice were used to demonstrate that fungi are regulated by host genetics and that diet has a regulatory role in the composition of gut fungi. The role of fungi in complex interactions involving host genetics, bacteria, and environmental factors remains understudied. Using whole genome sequencing and genotyping, quantitative trait loci associated with various fungal species were mapped in mice. Additionally, the study identified fungal indicator species associated with different dietary regimes.

NATURE COMMUNICATIONS (2023)

Review Medicine, General & Internal

Morphea: The 2023 update

Cristian Papara, David A. De Luca, Katja Bieber, Artem Vorobyev, Ralf J. Ludwig

Summary: Morphea, also known as localized scleroderma, is a chronic inflammatory connective tissue disorder that affects both adults and children. It is characterized by inflammation and fibrosis of the skin and underlying soft tissue, and in certain cases, can also affect surrounding structures. The etiology of morphea is still unknown, but genetic predisposition, vascular dysregulation, T(H)1/T(H)2 imbalance, cytokines, and certain environmental factors may contribute to its development. Proper assessment of disease activity and prompt initiation of treatment are crucial to prevent permanent damage.

FRONTIERS IN MEDICINE (2023)

Review Medicine, General & Internal

Lichen sclerosus: The 2023 update

David A. De Luca, Cristian Papara, Artem Vorobyev, Hernan Staiger, Katja Bieber, Diamant Thaci, Ralf J. Ludwig

Summary: Lichen sclerosus (LS) is an inflammatory mucocutaneous condition primarily affecting postmenopausal women, with unknown etiology. LS is associated with factors such as hormonal status, trauma, and autoimmune diseases. LS pathogenesis involves genetic predisposition, immune-mediated mechanisms, tissue remodeling genes, and oxidative stress. LS presents as chronic whitish atrophic patches with itching and soreness in the genital and anal regions. Treatment options include topical corticosteroids and calcineurin inhibitors. LS is a common dermatological disease with an incompletely understood pathogenesis and limited treatment options.

FRONTIERS IN MEDICINE (2023)

Article Dermatology

Inflammatory dermatoses in skin of color

Ralf J. Ludwig, Esther von Stebut

Summary: The epidemiology and clinical presentation of inflammatory dermatoses vary considerably between people with different colors of skin. It is important to know the epidemiology and recognize key clinical characteristics of these diseases in patients with skin of color (SOC) in order to provide excellent dermatological care for all patients.

DERMATOLOGIE (2023)

Article Dermatology

Bullous pemphigoid anti-BP180-NC16A autoantibody reactivity in healthy individuals is associated with marked hypovitaminosis D and Th2-like cytokine predominance

Stefan Tukaj, Katja Bieber, Wiebke Pruessmann, Jasper N. Pruessmann, Enno Schmidt, Detlef Zillikens, Ralf J. Ludwig, Michael Kasperkiewicz

Summary: Healthy individuals with BP autoantibody reactivity have abnormal vitamin D levels and a specific cytokine profile.

ARCHIVES OF DERMATOLOGICAL RESEARCH (2023)

Article Dermatology

Investigating the epidemiological relationship between vitiligo and psoriasis: a population-based study

Khalaf Kridin, Keren Lyakhovitsky, Erez Onn, Anna Lyakhovitsky, Ralf Ludwig, Orly Weinstein, Arnon D. Cohen

Summary: There is a bidirectional association between vitiligo and psoriasis.

ARCHIVES OF DERMATOLOGICAL RESEARCH (2023)

No Data Available