Clinical significance of rare serum autoantibodies in rheumatic diseases: a systematic literature review

Abstract

The identification of serum autoantibodies is central in the diagnosis of systemic autoimmune rheumatic disease (SARD), and an increasing number of specificities have been detected in the past years.This allows an early diagnosis in the active phases of diseases, with the identification of specific disease subsets that may ultimately improve the disease outcomes. Thanks to the use of old and new laboratory techniques that are becoming increasingly available worldwide, the number of rheumatic patients with a specific autoantibody is increasing and this is improving also our knowledge of disease trigger mechanisms.The paradigmatic example is the plethora of serum autoantibodies described in polymyositis and dermatomyositis, coined myositis-specific antibodies (MSA) which include antibodies directed against tRNA synthetases, anti-SRP, anti-Mi-2, and anti-TIF-1γ and can discriminate disease subtypes, particularly when associated with the risk of cancer. As a further example, anti-HMGCR antibodies have been reported in several studies in association with necrotizing autoimmune myositis that may follow statin use. To clarify the current knowledge on these rare specificities, we performed a systematic literature review. We focused on the main features associated to specific autoantibodies that are rarely identified in rheumatic disease, to increase the awareness and scientific knowledge on these autoantibodies in different ethnic groups worldwide. Inclusion criteriaObservational studies, case reports and clinical trials were included. Exclusion criteriaArticles not concerning SARD, and reviews or editorials in languages different from English, if including children or animals, were excluded to limit the literature review to adults and because no funding was available for translation. The selection process was performed by two authors, based on titles, abstracts and subsequently full text papers. Figure 1 represents the flowchart of the selection process of this systematic literature review. Data extractionThe year of publication, study design, number of patients and demographic data were recorded. The outcome was defined by the identification of rare autoAbs and their prevalence and clinical significance in SARD. Articles were divided into categories depending on the disease.

Systemic sclerosis in adults. Part I: Clinical features and pathogenesis

“…Estimated prevalence 24 SSc subtype Key cutaneous features [22][23][24]98 Key systemic features 13,[22][23][24]98 Demographic associations [22][23][24]98 HLA associations 99,100 Centromere (ACA)…”

Espectro Clínico dos Autoanticorpos TH/TO e NOR90 na Esclerose Sistémica

“…2,3 In more than 80% of the patients, autoantibodies have been identified years before the clinical onset of the disease, and therefore they are essential for an early diagnosis and treatment of these diseases. 1,4 Traditional classification of SSc defines this as diffuse or limited disease, depending on the extent of skin sclerosis. The clinical association with high-titer SSc patterns of ANA reactivity, generally mutually exclusive, allows to define the risk of specific complications, providing a complementary subgrouping for SSc that could enlighten therapeutic enhancements.…”

“…The 90-kDa autoantigen was later proved to be identical to human upstream-binding factor, an RNA polymerase I-specific transcription factor which plays a central role in transcriptional regulation of rRNA. 4 Based on search, NOR90 is present in ~5% of SSc cases with low specificity, since it's been also associated with other autoimmune conditions such rheumatoid arthritis, systemic lupus erythematosus; Sjögren's syndrome or neoplastic diseases. 1,5,8 We examined clinical and etiologic diagnosis associated to Anti-Th/To and NOR90 autoantibodies in a cohort of patients followed in an autoimmune consultation.…”