Histomorphometric Analysis of Cutaneous Remodeling in the Early Stage of the Scleroderma Model

Oliveira, Cristiane Carla de; Velosa, Ana Paula Pereira; Parra, Edwin R.; Capelozzi, Vera Luíza; Teodoro, Walcy Rosolia; Yoshinari, Natalino Hajime

doi:10.1590/s1807-59322009000600014

Cited by 10 publications

(15 citation statements)

References 19 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Further demonstration that morphological changes in rabbit skin have a distinct characteristic along the immunization process reinforces that tissue damage is dynamic and sequential. In fact, biopsies performed on days 7, 15 and 30 in animals submitted to immunization with collagen type V revealed that right after immunization, the endothelial basement membrane was disrupted [10]. Given that early lesions may have a key role in the underlying pathogenic process, authors speculated that epitopes of collagen type V were expressed as new antigens leading to the production of high titers of anti-collagen type V [7].…”

Section: Introductionmentioning

confidence: 99%

Anti-collagen type v: a marker of early systemic sclerosis?

et al. 2019

View full text Add to dashboard Cite

Objective: To evaluate the frequency of anti-collagen type V in humans with early systemic sclerosis (SSc) compared to defined SSc patients and healthy controls, since collagen type V was shown to be overexpressed in early SSc patients' skin and there is no data concerning the presence of this antibody in early stages of human SSc. Experimental studies showed that animal models immunized with collagen type V developed a disease similar to human systemic sclerosis (SSc), with antibodies production, mainly in early stages post-immunization. Methods: Eighty-one female SSc patients were included and divided into two groups: early-SSc (18 patients-EULAR Preliminary Criteria) and defined-SSc (63 patients-ACR Criteria 1980). The control group consisted of 19 healthy women age-matched to Early-SSc group. Anti-collagen type V was performed by ELISA. Data was analyzed by appropriate tests. Results: The prevalence of anti-collagen type V in early-SSc, defined-SSc and control groups was respectively 33, 17 and 5% (p = 0.07). SSc patients with anti-collagen type V had shorter disease duration compared to those without this antibody (8.8 ± 5.1 vs. 14.7 ± 8.9, p = 0.006). Likewise, early-SSc patients with anti-collagen V also had a shorter disease duration than patients negative for this antibody (4.6 ± 2.2 vs. 9.7 ± 5.2, p = 0.04). No association with clinical subsets or scleroderma antibodies specificities was observed (p > 0.05). Conclusion: The production of anti-collagen type V in SSc seems to be an early event independent of other antibodies specificities. Further studies are necessary to determine if the underlying mechanism for this chronology involves a primary immune response to abnormal expression of collagen type V.

show abstract

Section: Introductionmentioning

confidence: 99%

Anti-collagen type v: a marker of early systemic sclerosis?

et al. 2019

View full text Add to dashboard Cite

show abstract

“…We assume that the anti-V Col antibody could be a good marker to indicate vascular damage with subsequent matrix damage and exposure of hidden antigens as V Col fragments [3,[6][7][8]. We postulate that the SSc persistence of anti-V Col antibody occurs for a prolonged period lasting for a period of existence of matrix disorder with exposure of V Col anomalous which would coincide with the disease activity period.…”

Section: Discussionmentioning

confidence: 99%

“…In this context, the V Col found normally hidden between the heterotypical fibres (interlacement of collagen types I, III and V), but that is exposed when the inflammatory process occurs in the extracellular matrix. It would be the antigen itself (neo-antigen) responsible for triggering SSc animal and possibly human illness [3][4][5][6][7][8][9][10][11][12].…”

Section: Rheumatology: Current Researchmentioning

confidence: 99%

“…Other external toxic agents such as silica, similarly to V Col antigen inoculated in rabbits would cause injury of the endothelium -basal membrane complex [6,7,9] or bronchial epithelial -basal membrane complex [4,10], leading to vascular or bronchial damage, followed by intense inflammation process of the matrix, causing exposure of different antigens previously hidden from the immune system and thus would trigger the fibrosis and autoimmunity identified in SSc [4,6,7,10].…”

Section: Rheumatology: Current Researchmentioning

confidence: 99%

“…The earliest events observed in the pathogenesis of SSc is the damage to endothelial cells and apoptosis, demonstrated in skin and lungs, even before any evidence of autoimmunity or tissue fibrosis [4]. From the recent discovery of an experimental model of SSc in rabbits by immunization with type V collagen (V Col), was suggested that different forms of aggression to endothelial cells, provided that sufficiently prolonged and intense, would be able to promote damage in the endothelium -basal membrane complex, exposing the own extracellular matrix components to the immune system, triggering tissue histological alterations and autoimmunity observed in SSc [3][4][5][6][7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Anti-Collagen Type V Antibody in Systemic Sclerosis: A Possible Useful Tool to Asses Disease Activity

Horimoto¹,

Yoshinari²,

Mantovani³

et al. 2016

Rheumatology

View full text Add to dashboard Cite

Introduction: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular injury, autoimmunity and tissue fibrosis. Usually collagen type V (V Col) is found hidden between the heterotypical fibers. It was discovered in the rheumatology department at the University of São Paulo (FMUSP) that deposition of this collagen occurs, however with anomalous morphology in SSc patient's tissue, suggesting that V Col is an important molecule in fibrosis and autoimmunity process. The V Col molecule, which has atypical morphology aspect, exposed after a nonspecific inflammatory damage could result in formation of immune complexes (V Col-anti-V Col), whose deposition on the vascular endothelium, would cause a vascular damage, allowing the influx of cells of innate immunity into the extracellular matrix, resulting in an enzymatic degradation of the heterotypical fibers, with exposure of more V Col and perpetuation of the disease. Objectives: Assess whether there is a correlation between anti-V Col's presence in the serum of patients with SSc and indexes of activity, severity and quality of life measured by sHAQ. Methods: Were evaluated 60 patients with SSc diagnostic during the period of January to December 2014. Were applied Medsger severity criteria, Valentini activity criteria and health assessment questionnaire in SSc (sHAQ) in the patients, at initial assessment (baseline) and after 6 months, correlating the presence of anti-V Col with the clinical and laboratory manifestations found. Results: Most patients were female (98.3%) and had the limited form of the disease (43.3%), average age 51 years, white, average duration of nine years of disease and modified Rodnan Skin Score of 13.08. The main clinical manifestations observed in each organic system of patients were: skin thickening in the hands (78.3%), Raynaud's phenomenon (100%), arthritis (33.3%), oesophageal involvement (71.7%), interstitial lung disease (45%), pulmonary arterial hypertension (PAH) (19.4%) and scleroderma renal crisis (SRC) (1.7%). The most significant laboratory abnormalities were elevation of inflammatory markers in 41.7% of patients (ESR and CRP), CPK elevation (15%), low complement (C3 and C4) (3.3%), antinuclear antibody (95%), anti-centromere (41.7%), anti-DNA topoisomerase I antibody (26.7%), anti-RNA polymerase III (11.7%), anti-U1-RNP (16.7%) and anti-Ro (SSA) in 11.7% of patients. The anti-V Col was detected in 5 cases (8.3%) and showed statistical correlation with disease activity and scleroderma renal crisis, besides tendency to association with PAH; however, did not correlate with the severity index of disease or any other clinical manifestation, or with specific SSc antibodies. Conclusions: We suggest that disease activity in SSc patients could be determined by serological analysis, to detect the presence of V Col antibodies in the serum of patients with SSc, facilitating the approach of this serious disease. We suggest further studies with larger number of patients in order to confirm the usefulness of this new marker of di...

show abstract

Transcriptomic Evaluation of Juvenile Localized Scleroderma Skin With Histologic and Clinical Correlation

Schutt

Mirizio

Salgado

et al. 2021

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective Juvenile localized scleroderma (LS) is an autoimmune disease of the skin whose pathogenesis is not well understood due to the rarity of the disease. This study was undertaken to determine the skin transcriptome in skin biopsy tissue from children with juvenile LS compared to pediatric healthy controls, with identification of significant molecular targets using RNA sequencing (RNA‐Seq). In this study, differentially expressed genes (DEGs) were assessed for correlations with histopathologic and clinical features in children with juvenile LS, and were used to group the children into distinct genetic clusters based on immunophenotype. Methods RNA‐Seq was performed on sections of paraffin‐embedded skin tissue obtained from 28 children with juvenile LS and 10 pediatric healthy controls. RNA‐Seq was carried out using an Illumina HTS TruSeq RNA Access library prep kit, with data aligned using STAR and data analysis using a DESeq2 platform. A standardized histologic scoring system was used to score skin sections for the severity of inflammation and levels of collagen deposition. Histologic scoring was completed by 2 pathologists who were blinded with regard to the status of each sample. Spearman’s rank correlation coefficients were used to assess significant correlations between DEG expression profiles and skin histologic findings in patients with juvenile LS. Results We identified 589 significant DEGs in children with juvenile LS as compared to healthy controls. Hierarchical clustering was used to demonstrate 3 distinct juvenile LS immunophenotype clusters. The histologic scores of skin inflammation (based on numbers and categories of inflammatory cell infiltrates) were significantly correlated with the expression levels of HLA–DPB1, HLA–DQA2, HLA–DRA, and STAT1 genes (rs > 0.5, P < 0.01). Collagen thickness correlated with the expression levels of collagen organization genes as well as with genes found to be correlated with the severity of inflammation, including genes for major histocompatibility complex (MHC) class I, MHC class II, and interferon‐γ signaling. Conclusion Among children with juvenile LS, 3 distinct genetic signatures, or clusters, were identified. In one cluster, inflammation‐related pathways were up‐regulated, corresponding to the histologic skin inflammation score. In the second cluster, fibrosis‐related pathways were up‐regulated. In the third cluster, gene expression in the skin corresponded to the patterns seen in healthy controls. Up‐regulation of HLA class II genes was observed within the first cluster (characterized by predominant inflammation), a feature that has also been observed in the peripheral blood of patients with morphea and in the skin of patients with systemic sclerosis.

show abstract

Histomorphometric Analysis of Cutaneous Remodeling in the Early Stage of the Scleroderma Model

Cited by 10 publications

References 19 publications

Anti-collagen type v: a marker of early systemic sclerosis?

Anti-collagen type v: a marker of early systemic sclerosis?

Anti-Collagen Type V Antibody in Systemic Sclerosis: A Possible Useful Tool to Asses Disease Activity

Transcriptomic Evaluation of Juvenile Localized Scleroderma Skin With Histologic and Clinical Correlation

Contact Info

Product

Resources

About