Antinuclear antibodies in the relatives and spouses of patients with systemic sclerosis.

Abstract

SUMMARYThe families of 65 patients with systemic sclerosis were examined clinically and serum samples from each subject were tested for antinuclear antibodies (ANA) by immunofluorescence on HEp2 cells and for precipitating antibodies to soluble cellular antigens including Of 217 blood relatives, 58 (27%) had ANA (42 speckled, 13 nucleolar, one centromere, two homogeneous); 22 (10%) had precipitins, one anti-Scl-70, one anti-PM-Scl, one anti-nRNP, two anti-Ro(SSA), the remainder unidentified). Family members tended to share ANA patterns. Of 38 spouses, nine (24%) had ANA (all speckled) and two showed unidentified precipitins. This compares with an incidence of ANA and precipitins in a control population of 8% and 1% respectively. Antibodies were more common in female than male relatives (particularly in mothers and sisters of probands). Twenty one of the 58 family members with ANA had clinical features of connective tissue disease; the remainder were asymptomatic.The presence of genetic factors influencing autoimmunity is suggested by the incidence of autoantibodies in first degree relatives. Similar observations in spouses, however, indicate that environmental factors may also have a role in these immune abnormalities.Systemic sclerosis (SS) is a chronic disease characterised by prominent vascular involvement and progressive fibrosis of various organ systems of the body.

Genetic aspects of rheumatic diseases

“…The concordance among MZ twins is only 4.2% comparable to that observed in DZ twins (10) but this frequency is much higher than that in the general population, which has been estimated as 4.4/100 000 (9). However, MZ twins are 90% concordant for antinuclear antibodies (ANA) as compared to 40% in DZ twins (10), and relatives of patients with SSc are much more likely to have ANA than healthy controls (90,91). This suggests that the inherited genetic background is important for the development of autoantibodies but that the development of these antibodies and the presence of the underlying genetic background are themselves not sufficient for disease occurrence, and environmental factors must play a very important role (10).…”

Challenges and Controversies in Autoantibodies Associated with Systemic Rheumatic Diseases

“…This situation becomes even more complicated when it is appreciated that certain autoantibodies may precede the underlying disease for many years [11,12]. Furthermore, some autoantibodies are found in first degree relatives who may not develop disease features even after follow-up [13]. Therefore, when an autoantibody is detected that does not correspond to the expected clinical picture, it is unclear if the antibody predicts the long-term diagnosis of the patient, is a coincidental finding in a family member, or is simply a false positive finding.…”

How to use… antinuclear antibodies in paediatric rheumatic diseases

“…ANAs are directed against large nuclear complexes containing both protein and nucleic acid components 1. When associated with autoimmune disease, ANAs are often high-titre, high-affinity IgG antibodies produced by autoreactive B cells requiring T cell help and driven by host autoantigens 1.…”

“…When associated with autoimmune disease, ANAs are often high-titre, high-affinity IgG antibodies produced by autoreactive B cells requiring T cell help and driven by host autoantigens 1. In autoimmune disease, autoreactive T and B cells have escaped the multiple checkpoints of immune tolerance leading to autoantibody production, immune complex formation and systemic inflammation 4.…”

“…A variety of non-rheumatic conditions have been associated with a positive ANA including acute infection, drug and environmental exposures, malignancy and non-rheumatic autoimmune diseases, such as autoimmune thyroiditis, hepatitis, idiopathic thrombocytopenic purpura and myasthenia gravis 1 5 9–11 16. In addition, a positive ANA test occurs in between 3% and 32% of healthy individuals 5 7 16–18.…”