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

Ugolini-Lopes, Michelle Remião; Mantovani, Elenice; Bonoldi, Virgínia Lúcia Nazário; Medeiros-Ribeiro, Ana Cristina; Bonfá, Eloísa; Yoshinari, Natalino Hajime; Andrade, Danieli

doi:10.1186/s42358-019-0063-y

Cited by 4 publications

(4 citation statements)

References 12 publications

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“…This hypothesis can be supported by a previous study that showed an increase in a1(V) chain gene and protein expression in early-SSc skin prior to the increased expression of a1 of the types I and III collagen and persisting until the formation of the fibrotic scar (47). In addition, a higher percentage of anti-Col V antibodies was previously detected in the early-SSc stage compared to the defined-SSc (27). From a clinical point of view, we found a strong correlation in the anti-Col V autoantibodies with the time in which the first symptom of the disease started (see Supplementary Table 1).…”

Section: Discussionsupporting

confidence: 51%

“…Of note among the range of autoantibodies characteristic of SSc, anti-Col V antibodies were present in about 31% of the patients (25,26). Yet, a recent study described anti-Col V antibodies in 33% of the patients in the early stage of SSc (27). In addition to clinical findings, our group described a preclinical model for SSc using Col V immunization, which leads to histological, vascular and immunological changes similar to those observed in human SSc (28)(29)(30).…”

Section: Introductionmentioning

confidence: 89%

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Identification of Autoimmunity to Peptides of Collagen V α1 Chain as Newly Biomarkers of Early Stage of Systemic Sclerosis

et al. 2021

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Patients with Systemic sclerosis (SSc) presents immune dysregulation, vasculopathy, and fibrosis of the skin and various internal organs. Pulmonary fibrosis leads to SSc-associated interstitial lung disease (ILD), which is the main cause of morbidity and mortality in SSc. Recently autoimmunity to type V collagen (Col V) has been characterized in idiopathic pulmonary fibrosis and show promise to be related to the development in SSc. Our aim was to evaluate autoimmunity to Col V α1(V) and α2(V) chains and to the antigenic peptides of these Col V chains in early-SSc sera employing lung tissue of SSc-ILD, as antigen source. We found that sera samples from patients with early-SSc were reactive to Col V (41.18%) and presented immunoreactivity for Col5A1(1.049) and Col5A1(1.439) peptides. The IgG isolated from early-SSc patients-anti-Col V positive sera (anti-ColV IgG) was adsorbed with α1(V) chain (anti-ColV IgG/ads-α1(V)) and α2(V) chain (anti-ColV IgG/ads-α2(V)) and biotinylated to evaluate the spectrum of reactivity in SSc-ILD patients lung biopsies by immunofluorescence. The SSc-ILD lung tissue samples immunostained with anti-ColV IgG showed increased green fluorescence in the vascular basement membrane, bronchiolar smooth muscle, and adventitial layer, contrasting with the tenue immunostaining in control lungs. Col V protein expression in these pulmonary compartments immunostained with early-SSc anti-ColV IgG was confirmed by immune colocalization assays with commercial anti-human Col V antibodies. In addition, SSc-ILD lung tissues immunostained with anti-ColV IgG/ads-α1(V) (sample in which Col V α1 chain-specific antibodies were removed) showed decreased green fluorescence compared to anti-ColV IgG and anti-ColV IgG/ads-α2(V). Our data show that autoimmunity to Col V in early-SSc was related to peptides of the α1(V) chain, suggesting that these antibodies could be biomarkers of SSc stages and potential target of immunotherapy with Col V immunogenic peptides.

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 89%

Identification of Autoimmunity to Peptides of Collagen V α1 Chain as Newly Biomarkers of Early Stage of Systemic Sclerosis

et al. 2021

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“…Collagen V, a significant component of the extracellular matrix, has been specifically interrogated, and mice immunized with collagen V recapitulated the cutaneous, vascular and pulmonary manifestations of SSc [44]. Interestingly, anticollagen V antibodies were found in SSc patients, with a prevalence of 17-41% depending on disease stage, and were more prevalent early in disease and in younger patients [45,46]. Moreover, lung biopsies from SSc patients were found to have increased reactivity when stained with anticollagen V antibodies isolated from early SSc patients, compared to control tissue [45].…”

Section: Autoantibody Specificitymentioning

confidence: 99%

“…Downstream of the initial breach of tolerance, B cells coordinate the autoimmune response as antigen-presenting cells and as producers of autoantibodies, and recent work explores alterations in the signaling profiles and regulatory capacity of multiple B cell subsets [26 ▪▪ ,30,31 ▪ ]. Finally, newly-discovered autoantibodies may have predictive value or be involved in disease pathogenesis [35,36,43–53]. SSc, systemic sclerosis.…”

Section: Introductionmentioning

confidence: 99%

Insights into origins and specificities of autoantibodies in systemic sclerosis

Tiniakou

Crawford

Darrah

2021

Current Opinion in Rheumatology

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Purpose of reviewAutoantibodies are hallmark findings in systemic sclerosis (SSc), often present prior to disease onset. Clinical diagnosis and prognosis of SSc have long relied on the antitopoisomerase – anticentromere – anti-RNA polymerase antibody trichotomy. However, many more autoantibodies found in SSc are being actively investigated for insights into triggering events, mechanisms of tolerance break, and connections to tissue damage. This review examines recent studies on SSc autoantibodies and the early events that lead to their development.Recent findingsRecent work has elucidated potential connections between human cytomegalovirus infection, silicone breast implants, and malignancy to SSc autoantibody development. At the level of the dendritic cell:T cell interaction, where tolerance is broken, new studies identified shared motifs in the peptide-binding domains of SSc-associated human leukocyte antigen alleles. Immunological analysis of SSc patient B cells has uncovered several anomalies in the regulatory capacities of SSc naïve and memory B cell populations. Expanding efforts to uncover new SSc autoantibodies revealed anti-CXCL4, anticollagen V, and other autoantibodies as potential players in disease pathogenesis.SummaryFurther research into the role of autoantibodies in SSc development may uncover new mechanism-guided therapeutic targets. In addition, a better understanding of autoantibody associations with SSc disease outcomes will improve clinical care.

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