Title : Immunohistochemical characteristics of patients with Morphea at disease onset and advanced fibrotic stage
Abstract:
Relevance: Localized scleroderma, morphea, is a complex acquired autoimmune disease leading to dermal fibrosis. The issue of the pathogenesis from the group of collagenoses has been a topic of discussion since the mid-20th century. Immunohistochemical studies can help clarify the immunopathogenesis of the disease and also be useful in the differential diagnosis of morphea with clinically similar dermatoses.
Objective of the Study: To determine the expression levels of mediators of cellular and humoral immune responses, the activity of antibacterial and antiviral immune systems, as well as processes of fibrosis in patients with erythematous and fibrotic stages of morphea.
Materials and Methods: Based on the "Leningrad Regional Center," 50 patients were examined from 2010 to 2019, and they were divided into three groups. The first group consisted of 17 women and 3 men, with an average age of 35 years, diagnosed with morphea in the erythematous stage. The second group included 20 individuals (19 women and 1 man), with an average age of 33 years, diagnosed with limited scleroderma in the advanced fibrotic stage. The control group was formed from 10 individuals without skin pathology, 7 women and 3 men, with an average age of 40 years. Inclusion criteria for the experimental groups were clinical pictures characterized by the presence of widespread erythematous spots of reddish-brown color, often with a lilac halo, with clear boundaries, diameters up to 10 cm for patients in the first group. For the second group, criteria included induration of the lesion area, absence of hair follicles, and an ivory color in the center. All patients underwent punch biopsy using a tubular knife (punch) from the central and peripheral parts of the lesion. The biological material obtained was processed according to the recommendations of the antibody manufacturer R&D Systems and stained with the following markers: CD 4, CD 8, IL-2, IL-4, Vimentin, and TLR-7.
Results: In the skin biopsies of all patients in the initial stage, a markedly positive expression of CD4 and CD8 was found. In patients of the second group with advanced sclerotic stage of the disease, a pronounced reaction of CD4 lymphocytes and moderately expressed CD8 lymphocytes was noted. The expression of IL-2 was more pronounced among patients in the first group. However, IL-4 was intensely expressed in the dermis of patients in the second group. It should be noted that among the cellular composition of the dermal infiltrate in patients with the erythematous stage of morphea, lymphocytes predominated, while in the second group, plasma cells were predominant. A pronounced expression of Vimentin was observed in 16 out of 20 patients with advanced fibrotic stage, while the remaining members of the second group exhibited moderately expressed Vimentin. In most patients of the first group, positive expression of TLR7 was noted, while in patients of the second group, it was less pronounced.
Conclusions: In the initial stage, the prevailing expressions are IL-2, CD4 and CD8 cells. As the disease progresses and transitions to the fibrotic stage, the prevailing tissue markers change to IL-4 and Vimentin. Based on the results obtained, a shift from cellular autoimmune reactions to humoral ones is evident. However, the mechanism of this switch remains a subject of study. Toll-like receptor 7 appears to be a precursor to the manifestation of collagenoses, being more intensely expressed among patients in the first group with a recent onset of the disease. Furthermore, toll-like receptor 7 plays a role in potentiating, that is, stimulating cellular reactions, which is expressed in increased expression in patients of the first group.
Audience Takeaway:
Based on the information provided regarding the immunohistochemical characteristics of patients with morphea, the audience (which may include researchers, clinicians, students, and educators in the fields of dermatology, immunology, and autoimmune diseases) can benefit in several ways:
1. Improved Understanding of Disease Mechanisms: The audience will gain insights into the immunopathogenesis of morphea, enhancing their understanding of how the disease develops and progresses. This knowledge can lead to better patient management and treatment strategies.
2. Enhanced Diagnostic Criteria: Results from the study, including the expression levels of various markers (e.g., CD4, CD8, interleukins, Vimentin), can aid clinicians in distinguishing morphea from other clinically similar dermatoses, thus improving diagnostic accuracy.
3. Application in Research and Teaching: Faculty and researchers could use these findings to expand their research into autoimmune diseases and related pathways. Additionally, this information can serve as educational material in courses focused on dermatology, immunology, and rheumatology, improving the curriculum quality.
4. Development of Targeted Therapies: Understanding the specific immune responses and markers associated with morphea may lead to the development of targeted therapies. Clinicians might implement more effective treatment plans based on the unique characteristics of the disease phases.
5. Practical Solutions for Clinical Practice: With the identification of specific biomarkers, clinicians can streamline their diagnostic processes, potentially leading to more efficient patient care. This could reduce the time and resources spent on confirming a diagnosis. Plus, by identifying stages of the disease accurately, treatments can be adjusted in a timely manner to improve patient outcomes.
Other Benefits:
- Collaboration Potential: The research may foster collaborations across various disciplines (dermatology, immunology, histopathology) leading to multidisciplinary approaches to treatment.
- Informed Patient Management: Providers will be better equipped to explain the disease process to patients, fostering improved patient education and compliance.
- Future Research Directions: The study highlights potential new areas for investigation, providing a roadmap for future research into morphea and related conditions.
- Contribution to Literature: Findings from this research could contribute significantly to the scientific literature regarding localized scleroderma, helping to fill gaps in knowledge and inform future studies.
This comprehensive understanding and application of the research can ultimately lead to significant improvements in patient care and outcomes, while also contributing positively to academic and clinical settings.
