Review
Immunology
Reza Akbarzadeh, Antje Mueller, Jens Y. Humrich, Gabriela Riemekasten
Summary: Systemic sclerosis (SSc) is a chronic autoimmune disease with complex features such as autoimmunity, vasculopathy, and fibrosis. Antibodies targeting G protein-coupled receptors (GPCRs) have been found to play a role in SSc pathologies. Understanding the effects of GPCR antibodies in SSc could contribute to the development of therapeutic strategies targeting these receptors.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Clinical Neurology
Maija Orjatsalo, Eemil Partinen, Gerd Wallukat, Anniina Alakuijala, Markku Partinen
Summary: The study found that patients with narcolepsy type 1 carry autoimmune antibodies that may be related to symptoms such as cataplexy, hallucinations, pain, and autonomic dysfunction. Positive autoantibodies against M2 muscarinic receptors, nociception receptors, and beta 2 adrenergic receptors may exacerbate the progression of the disease.
Article
Immunology
Aurelien Chepy, Solange Vivier, Fabrice Bray, Camille Ternynck, Jean-Pascal Meneboo, Martin Figeac, Alexandre Filiot, Lucile Guilbert, Manel Jendoubi, Christian Rolando, David Launay, Sylvain Dubucquoi, Guillemette Marot, Vincent Sobanski
Summary: This study investigated the effect of purified immunoglobulin G (IgG) from systemic sclerosis (SSc) patients on protein and mRNA expression of dermal fibroblasts (FBs) using a multi-omics approach. The results showed that SSc sera and purified IgG induced unique protein profile patterns, and this effect depended on the serotype of the patient.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Raudah Lazim, Donghyuk Suh, Jai Woo Lee, Thi Ngoc Lan Vu, Sanghee Yoon, Sun Choi
Summary: The presence of GPCR dimers has sparked research into their importance in disease pathogenesis and drug design, uncovering new signaling pathways and potential therapeutic targets. The increasing influence of computational methods in research is providing new avenues for understanding the functions and interactions of GPCRs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Engineering, Biomedical
Lei Lu, Shammy Raj, Narcy Arizmendi, Jie Ding, Gary Eitzen, Peter Kwan, Marianna Kulka, Larry D. Unsworth
Summary: Peptide-based therapeutics are highly specific but can fail in clinical testing due to inflammatory responses, with mast cells playing a key role in this process. Activation of mast cells through MRGPRX2, independent of Fc epsilon RI, is a significant factor in drug trial failures. Identifying peptide sequences that activate mast cells through MRGPRX2 can help reduce failure rates and design peptides with desired mast cell activation. Studies have found specific amino acid sequences that induce mast cell activation through MRGPRX2, allowing for the design of artificial peptides with varying activation potentials.
ACTA BIOMATERIALIA
(2021)
Article
Rheumatology
Sabrina Hoa, Selma Lazizi, Murray Baron, Mianbo Wang, Marvin J. Fritzler, Marie Hudson
Summary: There is an association between cancer and specific autoantibodies in SSc patients, with increased cancer risk in patients positive for anti-topoisomerase I and anti-U1-RNP antibodies. However, synchronous cancer is rare in this cohort of Canadian SSc patients.
Article
Biology
Sevdalina Nikolova Lambova, Ekaterina Krasimirova Kurteva, Sanie Syuleymanova Dzhambazova, Georgi Hristov Vasilev, Dobroslav Stanimirov Kyurkchiev, Mariela Gencheva Geneva-Popova
Summary: In this pilot study involving 19 patients with SSc, a correlation between more advanced capillaroscopic changes and the presence of anti-Scl-70 autoantibodies was confirmed. Additionally, positive anti-RNAP III-155 antibodies were found in SSc patients with or without early microangiopathy.
Article
Rheumatology
Kristina Elizabeth Neergaard Clark, Corrado Campochiaro, Eszter Csomor, Adam Taylor, Katherine Nevin, Nicholas Galwey, Mary A. Morse, Jennifer Singh, Yee Voan Teo, Voon H. Ong, Emma Derrett-Smith, Nicolas Wisniacki, Shaun M. Flint, Christopher P. Denton
Summary: Clinical heterogeneity is a key feature of systemic sclerosis (SSc), with hallmark SSc autoantibodies playing a central role in diagnosis and associating with distinct patterns of complications. This study used high-dimensional transcriptional and proteomic analysis to reveal a molecular spectrum of SSc based on skin gene expression and serum protein analysis, showing differences in fibrosis markers and gene expression profiles between different autoantibody specificities. Individual patient pathway analysis identified overlapping and distinct disease processes within SSc subgroups.
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Review
Cell Biology
Haoran Jiang, Daniella Galtes, Jialu Wang, Howard A. Rockman
Summary: This review explores the signaling pathways, dynamic structures, and physiological relevance of the three most important GPCR signaling effectors in the cardiovascular system: heterotrimeric G proteins, GPCR kinases (GRKs), and 8-arrestins. It summarizes their prominent roles in GPCR pharmacology before transitioning into less well-explored areas. The application of new technologies has contributed to an increasing understanding of GPCR structure and downstream effectors.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Stephen P. H. Alexander, Arthur Christopoulos, Anthony P. Davenport, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Adam J. Pawson, Christopher Southan, Jamie A. Davies, Maria Pia Abbracchio, Wayne Alexander, Khaled Al-hosaini, Magnus Baeck, Nicholas M. Barnes, Ross Bathgate, Jean-Martin Beaulieu, Kenneth E. Bernstein, Bernhard Bettler, Nigel J. M. Birdsall, Victoria Blaho, Francois Boulay, Corinne Bousquet, Hans Braeuner-Osborne, Geoffrey Burnstock, Girolamo Calo, Justo P. Castano, KevinJ Catt, Stefania Ceruti, Paul Chazot, Nan Chiang, Bice Chini, Jerold Chun, Antonia Cianciulli, Olivier Civelli, Lucie H. Clapp, Rejean Couture, Zsolt Csaba, Claes Dahlgren, Gordon Dent, Khuraijam Dhanachandra Singh, Steven D. Douglas, Pascal Dournaud, Satoru Eguchi, Emanuel Escher, Edward J. Filardo, Tung Fong, Marta Fumagalli, Raul R. Gainetdinov, Marc de Gasparo, Craig Gerard, Marvin Gershengorn, Fernand Gobeil, Theodore L. Goodfriend, Cyril Goudet, Karen J. Gregory, Andrew L. Gundlach, Joerg Hamann, Julien Hanson, Richard L. Hauger, Debbie L. Hay, Akos Heinemann, Morley D. Hollenberg, Nicholas D. Holliday, Mastgugu Horiuchi, Daniel Hoyer, Laszlo Hunyady, Ahsan Husain, Adriaan P. IJzerman, Tadashi Inagami, Kenneth A. Jacobson, Robert T. Jensen, Ralf Jockers, Deepa Jonnalagadda, Sadashiva Karnik, Klemens Kaupmann, Jacqueline Kemp, Charles Kennedy, Yasuyuki Kihara, Takio Kitazawa, Pawel Kozielewicz, Hans-Juergen Kreienkamp, Jyrki P. Kukkonen, Tobias Langenhan, Katie Leach, Davide Lecca, John D. Lee, Susan E. Leeman, Jerome Leprince, Xaria X. Li, Tom Lloyd Williams, Stephen J. Lolait, Amelie Lupp, Robyn Macrae, Janet Maguire, Jean Mazella, Craig A. McArdle, Shlomo Melmed, Martin C. Michel, Laurence J. Miller, Vincenzo Mitolo, Bernard Mouillac, Christa E. Mueller, Philip Murphy, Jean-Louis Nahon, Tony Ngo, Xavier Norel, Duuamene Nyimanu, Anne-Marie Ocarroll, Stefan Offermanns, Maria Antonietta Panaro, Marc Parmentier, Roger G. Pertwee, Jean-Philippe Pin, Eric R. Prossnitz, Mark Quinn, Rithwik Ramachandran, Manisha Ray, Rainer K. Reinscheid, Philippe Rondard, G. Enrico Rovati, Chiara Ruzza, Gareth J. Sanger, Torsten Schoeneberg, Gunnar Schulte, Stefan Schulz, Deborah L. Segaloff, Charles N. Serhan, Leigh A. Stoddart, Yukihiko Sugimoto, Roger Summers, Valerie P. Tan, David Thal, Walter (Wally) Thomas, PieterB M. W. M. Timmermans, Kalyan Tirupula, Giovanni Tulipano, Hamiyet Unal, Thomas Unger, Celine Valant, Patrick Vanderheyden, David Vaudry, Hubert Vaudry, Jean-Pierre Vilardaga, Christopher S. Walker, Ji Ming Wang, Donald T. Ward, Hans-Juergen Wester, Gary B. Willars, Trent M. Woodruff, Chengcan Yao, Richard D. Ye
Summary: The Concise Guide to PHARMACOLOGY 2021/22 presents concise overviews of nearly 1900 human drug targets with an emphasis on selective pharmacology, along with links to a more detailed knowledgebase. It serves as a permanent, citable record for researchers, providing useful information in the field of pharmacology.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Estefania Moreno, Nil Casajuana-Martin, Michael Coyle, Baruc Campos Campos, Ewa Galaj, Claudia Llinas del Torrent, Arta Seyedian, William Rea, Ning-Sheng Cai, Alessandro Bonifazi, Benjamin Floran, Zheng-Xiong Xi, Xavier Guitart, Vicent Casado, Amy H. Newman, Christopher Bishop, Leonardo Pardo, Sergi Ferre
Summary: This study provides evidence that heteromerization of G protein-coupled receptors (GPCRs), specifically dopamine D1 and D3 receptors, can influence the pharmacological properties of selective ligands. In vivo experiments support the involvement of D1R-D3R heteromers in the development of L-DOPA-induced dyskinesia in Parkinson's disease, suggesting the potential of targeting GPCR heteromers for drug development.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Medicine, General & Internal
Helma Freitag, Marvin Szklarski, Sebastian Lorenz, Franziska Sotzny, Sandra Bauer, Aurelie Philippe, Claudia Kedor, Patricia Grabowski, Tanja Lange, Gabriela Riemekasten, Harald Heidecke, Carmen Scheibenbogen
Summary: The study found that levels of specific AAB were significantly correlated with fatigue and muscle pain symptoms in patients with infection-triggered ME/CFS, while patients with non-infection-triggered ME/CFS showed fewer correlations. This suggests a potential role of AAB or respective receptor pathways in the pathomechanism of the disease.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Juergen Einsiedel, Maximilian F. Schmidt, Harald Huebner, Peter Gmeiner
Summary: A broadly applicable synthesis method was developed for peptides incorporating mixed disulfides between cysteine and homocysteine and cysteamine. The method was successfully applied to pharmacologically relevant GPCR ligands and showed covalent binding to neurotensin receptor 1 in a radioligand depletion study.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Ilana B. Kotliar, Emily Lorenzen, Jochen M. Schwenk, Debbie L. Hay, Thomas P. Sakmar
Summary: G protein-coupled receptors (GPCRs) interact with a variety of membrane proteins, but the extent and mechanisms of these interactions are not well understood. RAMPs, a class of GPCR-interacting proteins, have been extensively studied. Recent research suggests that GPCR-RAMP interactions may be more widespread than previously thought. This review summarizes the latest techniques for discovering GPCR-RAMP interactions and their functional consequences, and discusses future research prospects.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Rheumatology
Burcu Ayoglu, Michele Donato, Daniel E. Furst, Leslie J. Crofford, Ellen Goldmuntz, Lynette Keyes-Elstein, Judith James, Susan Macwana, Maureen D. Mayes, Peter McSweeney, Richard A. Nash, Keith M. Sullivan, Beverly Welch, Ashley Pinckney, Rong Mao, Lorinda Chung, Purvesh Khatri, Paul J. Utz
Summary: Results from the SCOT clinical trial showed that HSCT had significant benefits over CTX in patients with systemic sclerosis. The objective of this study was to test the hypothesis that transplantation stabilizes the autoantibody repertoire in patients with favorable clinical outcomes. Analysis of autoantibody profiles revealed significant differences between HSCT and CTX-treated patients, suggesting that HSCT alters the autoantibody repertoire while CTX treatment does not.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Dermatology
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
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
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
Christoph M. Hammers
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Article
Dermatology
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
Khalaf Kridin, Noor Mruwat, Diamant Thaci, Ralf J. Ludwig
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Review
Veterinary Sciences
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
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.
Article
Immunology
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
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
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
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
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.
Article
Dermatology
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
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)