Six recombinant antibodies specifically distinguish native, citrullinated, and carbamylated LL-37 forms — enabling detection in lupus and RA patient samples.
6 antibodiesspecifically distinguish native, citrullinated, and carbamylated LL-37 — enabling precise measurement in autoimmune disease
What the researchers found
Six recombinant antibodies (MRB137-MRB142) were produced as monovalent mouse antibodies with scFv portions fused to mouse IgG2a Fc. These antibodies can specifically recognize either native LL37 or citrullinated LL37 and do not cross-react with carbamylated LL37.
Using ELISA, the antibodies detected native LL37 or citrullinated LL37 in serum samples from SLE and rheumatoid arthritis patients. Immunohistochemistry detected these forms in skin tissue from cutaneous lupus patients.
These antibodies are previously unavailable tools that can now be used to study the relationship between post-translationally modified LL37 and immune system activation in chronic autoimmune diseases.
Why it matters
Modified forms of LL37 are increasingly recognized as important in autoimmune diseases, but until now there were no antibodies that could reliably tell them apart. These tools will enable researchers to study which form of LL37 is present in different diseases and tissues, potentially leading to better biomarkers and targeted therapies.
The numbers in context
6 antibodies (MRB137-142); native vs cit-LL37 discrimination; ELISA + IHC validation in SLE, RA, cutaneous lupus
How the study worked
Researchers generated recombinant antibodies using phage display, produced them as scFv-Fc fusions, and characterized their specificity against native, citrullinated, and carbamylated LL37. They tested the antibodies in ELISA with patient sera and immunohistochemistry on lupus skin tissue.
Who was studied
Lupus and rheumatoid arthritis patients (proof-of-concept)
What this study cannot tell us
This is a tool development paper. The antibodies' diagnostic utility and clinical value need to be validated in larger patient cohorts.
The study did not determine whether the levels of native vs citrullinated LL37 predict disease activity or treatment response.
How to read the evidence
Moderate evidence as a tool development paper. Antibody specificity validated, but clinical diagnostic utility not yet established.
When this study was published
Published in 2020. These tools should enable further research into LL-37 modifications in autoimmune diseases.
The bigger picture
Modified LL-37 is increasingly recognized as important in autoimmune diseases, but until now there were no tools to tell the forms apart. These antibodies enable precise measurement of each LL-37 variant, potentially leading to biomarkers for disease activity and treatment response.
Questions still open
- Are native and citrullinated LL-37 levels useful prognostic markers?
- Does treatment change the ratio of LL-37 forms?
- Can these antibodies be developed into clinical diagnostic assays?
Common questions
Why do different forms of LL-37 matter?
Could these become diagnostic tests?
Read the original research
Generation of Monoclonal Antibodies Specific for Native LL37 and Citrullinated LL37 That Discriminate the Two LL37 Forms in the Skin and Circulation of Cutaneous/Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients.
Antibodies (Basel, Switzerland), 9(2)
Citation
Lande, Roberto; Palazzo, Raffaella; Hammel, Philippe; Pietraforte, Immacolata; Surbeck, Isabelle; Gilliet, Michel; Chizzolini, Carlo; Frasca, Loredana. (2020). Generation of Monoclonal Antibodies Specific for Native LL37 and Citrullinated LL37 That Discriminate the Two LL37 Forms in the Skin and Circulation of Cutaneous/Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients.. Antibodies (Basel, Switzerland), 9(2). https://doi.org/10.3390/antib9020014