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Detection of autoimmune antibodies in localized scleroderma by synthetic oligonucleotide antigens.

ABSTRACT: In this study, we developed a series of synthetic oligonucleotides that allowed us to investigate the details on the antigen recognition by autoimmune antibodies in localized scleroderma subjects. Besides dramatically improved analytical specificity of the assay, our data suggests a potential linking for antibodies to DNA to the biological status of disease state in localized scleroderma. Moreover, introducing chemical modifications into short synthetic deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) molecules completely changed the binding titers of corresponding antibodies and their clinical relevance. The strongest observed effect was registered for the localized scleroderma skin damage index (LoSDI) on the IgG antibodies to TC dinucleotide-rich double-stranded antigen (p < 0.001). In addition to providing valuable tools for diagnosis of clinically relevant biomarkers, we believe that this work opens up new opportunities for research on antibodies to nucleic acids in localized scleroderma and other autoimmune diseases.

SUBMITTER: Samuelsen S

PROVIDER: S-EPMC5895021 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Detection of autoimmune antibodies in localized scleroderma by synthetic oligonucleotide antigens.

Samuelsen Simone S Jørgensen Christian Damsgaard CD Mellins Elizabeth D ED Torok Kathryn S KS Astakhova Kira K

PloS one 20180411 4

In this study, we developed a series of synthetic oligonucleotides that allowed us to investigate the details on the antigen recognition by autoimmune antibodies in localized scleroderma subjects. Besides dramatically improved analytical specificity of the assay, our data suggests a potential linking for antibodies to DNA to the biological status of disease state in localized scleroderma. Moreover, introducing chemical modifications into short synthetic deoxyribonucleic acid (DNA) and ribonuclei ...[more]

PMID: 29641558

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Project description:BackgroundConnective tissue nevi (CTN) are congenital hamartomas caused by excessive proliferation of dermis components. In children, CTN can mimic juvenile localized scleroderma (JLS), an immune mediated skin disorder that requires aggressive immunosuppression.ObjectivesAim of our study was to describe a series of pediatric patients with CTN misdiagnosed as JLS and the discerning characteristics between the two conditions.MethodsRetrospective analysis of children referred to our Center during the last two decades for JLS who received a final diagnosis of CTN. Clinical, laboratory, histopathological and instrumental data (MRI and thermography) were collected and compared with those with JLS.ResultsSeventeen patients with mean age at onset 4.6 years entered the study. All came to our Center with a certain diagnosis of JLS (n = 15) or suspected JLS (n = 2). The indurated skin lesions were flat and resembled either circumscribed morphea or pansclerotic morphea. In 14 patients (82.4%) they were mainly localized at the lower limbs and in three (17.6%) at the upper limbs. No patient had laboratory inflammatory changes or positive autoantibodies. Skin biopsies confirmed the diagnosis of CTN: non-familial collagenoma in eleven (64.7%), mixed CTN in four (23.5%) and familial CTN in two (11.8%). Mean age at final diagnosis was 9.5 years, with a mean diagnostic delay of 4.8 years (range 1-15 years). Sixteen patients underwent musculoskeletal MRI that was normal in all except two who showed muscle perifascial enhancement. Thermography was normal in all patients. At our first evaluation, eleven patients (64.7%) were on systemic treatment (methotrexate 11, corticosteroids 7, biologics 2), three (17.6%) on topical corticosteroids and three untreated.ConclusionsCTN can be misdiagnosed as JLS and therefore aggressively treated with prolonged and inappropriate immunosuppression. The absence of inflammatory appearance of the skin lesions, normal instrumental and laboratory findings and the accurate evaluation of skin biopsy are crucial to address the right diagnosis.

Dataset Information

Detection of autoimmune antibodies in localized scleroderma by synthetic oligonucleotide antigens.

Publications

Detection of autoimmune antibodies in localized scleroderma by synthetic oligonucleotide antigens.

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