1. “Characterization of Active MMP9 in Chronic Inflammatory Diseases Using a Novel Anti-MMP9 Antibody”
by Maile Velasquez, Chris O’Sullivan, Robert Brockett, Amanda Mikels-Vigdal, Igor Mikaelian, Victoria Smith and Andrew E. Greenstein
Antibodies 2023, 12(1), 9; https://doi.org/10.3390/antib12010009
Available online: https://www.mdpi.com/2073-4468/12/1/9

Cover Story: Matrix metalloproteinase 9 (MMP9), a protease implicated in multiple diseases, is secreted as an inactive zymogen and requires proteolytic removal of the pro-domain for activation. The relative levels and functionality of the pro- and active-MMP9 isoforms in tissues are not characterized. We generated a specific antibody that distinguishes an active form of MMP9, F107-MMP9, from the inactive pro-MMP9 isoform. Using multiple in vitro assays and specimen types, we show that F107-MMP9 expression is localized and disease-specific compared with its more abundant parental pro-form. It is detected around sites of active tissue remodeling, including fistulae of inflammatory bowel and dermal fissures in hidradenitis suppurativa, and is expressed by myeloid cells, including macrophages and neutrophils.

2. “CCR6 as a Potential Target for Therapeutic Antibodies for the Treatment of Inflammatory Diseases”
by Sara Gómez-Melero and Javier Caballero-Villarraso
Antibodies 2023, 12(2), 30; https://doi.org/10.3390/antib12020030
Available online: https://www.mdpi.com/2073-4468/12/2/30

Cover Story: The CC chemokine receptor 6 (CCR6) is a G protein-coupled receptor (GPCR) involved in a wide range of biological processes. When CCR6 binds to its sole ligand CCL20, a signaling network is produced. This pathway is implicated in mechanisms related to many diseases, such as cancer, psoriasis, multiple sclerosis, HIV infection or rheumatoid arthritis. The CCR6/CCL20 axis plays a fundamental role in immune homeostasis and activation. Th17 cells express the CCR6 receptor and inflammatory cytokines, including IL-17, IL-21 and IL-22, which are involved in the spread of inflammatory response. The CCL20/CCR6 mechanism plays a crucial role in the recruitment of these pro-inflammatory cells to local tissues.

3. “Expanding the Reach of Monoclonal Antibodies: A Review of Synthetic Nucleic Acid Delivery in Immunotherapy”
by Christopher Chung, Sagar B. Kudchodkar, Curtis N. Chung, Young K. Park, Ziyang Xu, Norbert Pardi, Mohamed Abdel-Mohsen and Kar Muthumani
Antibodies 2023, 12(3), 46; https://doi.org/10.3390/antib12030046
Available online: https://www.mdpi.com/2073-4468/12/3/46

Cover Story: Harnessing the immune system to combat disease has revolutionized medical treatment. Monoclonal antibodies (mAbs), in particular, have emerged as important immunotherapeutic agents with clinical relevance in treating a wide range of diseases, including allergies, autoimmune diseases, neurodegenerative disorders, cancer, and infectious diseases. These mAbs are developed from naturally occurring antibodies and target specific epitopes of single molecules, minimizing off-target effects. Antibodies can also be designed to target particular pathogens or modulate immune function by activating or suppressing certain pathways. Despite the benefit for patients, the production and administration of monoclonal antibody therapeutics are laborious, costly, and time-consuming.

4. “Antibody Cross-Reactivity in Serodiagnosis of Lyme Disease”
by Weronika Grąźlewska and Lucyna Holec-Gąsior
Antibodies 2023, 12(4), 63; https://doi.org/10.3390/antib12040063
Available online: https://www.mdpi.com/2073-4468/12/4/63

Cover Story: Lyme disease is a tick-borne disease caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex. The disease is characterized by a varied course; therefore, the basis for diagnosis is laboratory methods. Currently, a two-tiered serological test is recommended, using an ELISA as a screening test and a Western blot as a confirmatory test. This approach was introduced due to the relatively high number of false-positive results obtained when using an ELISA alone. However, this approach has not entirely solved the problem of false-positive results caused by cross-reactive antibodies. Many highly immunogenic B. burgdorferi s.l. proteins are recognized nonspecifically by antibodies directed against other pathogens.