Autoantibodies In Rheumatic Diseases Research Articles

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

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.

Editorial introductions

Editorial introductions

Different types of autoantibodies in rheumatic diseases and methods of their determination

Rheumatic diseases are a group of chronic disorders with varied and frequently unexplained autoimmune etiology. They results from an immune response targeted against own antigens in the autoimmune process. Arising autoantibodies bind to the autoantigen, ultimately leading to cell and tissue damage. Rheumatic diseases are characterized by the presence of antibodies exhibiting a specific antigenic activity which is useful for making the correct diagnosis. There is a known correlation between the certain autoantibodies, so-called marker autoantibodies, and specific clinical findings. Autoantibodies from this group have a high diagnostic and prognostic value. It must be emphasized that the detection of antibody in the blood serum is not in itself sufficient for diagnosis a disease, if no clinical symptoms are present. A major role in the immune diagnostics of rheumatic diseases is played by serological tests, primarily the indirect immunofluorescence assay, the last one being recognized as a gold standard in antinuclear antibodies detection. This thesis contains a description of different types of antibodies found in rheumatic disorders, an evaluation of their clinical usefulness and immunodiagnostic methods of their determination.

High Ro52 Expression in Spontaneous and UV-Induced Cutaneous Inflammation

Ro52 is an E3 ubiquitin ligase with a recently identified regulatory role in inflammation. The protein is targeted by autoantibodies in rheumatic diseases, and Ro52 autoantibodies are specifically associated with cutaneous lupus erythematosus (CLE) and photosensitivity. The aim of this study was to investigate cutaneous Ro52 expression in CLE patients and to examine whether UVR might modulate Ro52. Ro52 expression was assessed by immunohistochemistry in biopsies derived from CLE lesions (n=25), nonlesional (n=7), and healthy control skin using four anti-Ro52 mAbs generated by us. Ro52 expression was also analyzed in psoriatic, lichenoid, and eczematous lesions. It was increased in the epidermis of spontaneous CLE lesions as compared with unaffected skin of patients and healthy controls. High epidermal Ro52 expression was also observed in other inflammatory dermatoses investigated. Ro52 was upregulated in experimentally photoprovoked CLE lesions as observed by immunohistochemistry in sequential biopsies, which was confirmed in vitro both at the mRNA and protein levels by exposing cultured patient-derived primary keratinocytes to UVR. In conclusion, Ro52 expression is upregulated in keratinocytes in inflammatory skin conditions and in response to UVR. High Ro52 expression might lead to the breaking of tolerance and the generation of Ro52 autoantibodies in genetically susceptible subjects. Further, the upregulation of Ro52 in keratinocytes after sun exposure might also be a triggering factor for skin lesions in patients with Ro52 antibodies.

Anti-interleukin-6 autoantibodies in rheumatic diseases. Increased frequency in the sera of patients with systemic sclerosis.

To investigate the presence and the roles of anti-interleukin-6 (anti-IL-6) autoantibodies in rheumatic diseases, and to further elucidate clinical and pathophysiologic significance of anticytokine autoantibodies. Anti-IL-6 IgG autoantibodies were measured by the 125I-IL-6 binding activity of IgG, which was isolated from serum by protein A-Sepharose. Nine of 52 sera (17.3%) from patients with systemic sclerosis (SSc) contained anti-IL-6 antibodies, whereas only 1.9% of sera from normal subjects and 0-5% of sera from patients with other rheumatic diseases were positive for the antibodies. Moreover, anti-IL-6 autoantibodies were found predominantly among patients with the limited form of SSc (42.9%), compared with those with the diffuse form (7.9%). Anti-IL-6 IgG autoantibodies were detected in patients with SSc, particularly those with the limited form of the disease, at a significantly increased frequency compared with normal subjects and patients with other rheumatic diseases. These results suggest that the development of anti-IL-6 autoantibodies and IL-6 may have a role in the pathophysiology of SSc.

ANTIBODIES TO HISTONES IN SYSTEMIC LUPUS ERYTHEMATOSUS AND DRUG-INDUCED LUPUS SYNDROMES

Antihistone antibodies are some of the most frequent autoantibodies in rheumatic diseases and can represent useful diagnostic markers in some autoimmune syndromes. Histone epitopes are often located in accessible regions of chromatin or are conformational determinants resulting from the association of several components. These observations and studies with murine models of lupus strongly support the view that histones play a direct stimulatory role in triggering autoantibody production.