Antibodies to various autoantigens may be present in sera of patients who will develop Lupus erythematosus up to seven years before onset of disease symptoms
Autoantibodies are specific and sensitive biomarkers for autoimmune diseases and indispensible diagnostic tools. They may also be involved in pathogenic processes underlying the disease and will potentially occur in sera of apparently healthy people long before onset of the first symptoms.
C. Eriksson, S. Raantapaa-Dalquist and their colleagues from Umeå University in Sweden have focused on this preclinical phase in the development of Systemic Lupus Erythematosus (SLE).
Catharina Eriksson, Heidi Kokkonen, Martin Johansson, Goran Hallmans, Goran Wadell, and Solbritt Rantapaa-Dahlqvist.
Autoantibodies predate the onset of Systemic Lupus Erythematosus in northern Sweden.
Arthritis Research & Therapy 2011, 13 (1):R30.
The Swedish scientists performed a comprehensive study of the autoantibody profiles before disease onset and after diagnosis in 35 patients who had donated blood before the first disease symptoms occurred and in 152 age- and sex-matched healthy subjects from northern Sweden. They investigated the production of autoantibodies that bind to major autoantigens associated with the disease, e.g. anti-Ro/SSA, anti-La/SSB, anti-Sm, anti-RNP, anti-Scl70, anti-Jo-1, anti-dsDNA, anti-centromere protein B, anti-histone and antinuclear antigens. These antibodies were then correlated to the first recorded symptom of the disease.
In 63% of the 35 pre-symptomatic individuals autoantibodies could be detected before onset of disease symptoms by a median of 4.2 years. Ten of these patients expressed one autoantibody, 12 had two or more autoantibodies. The sensitivity was highest for ANA at 45.7 % with a specificity of 95 %, followed by anti-dsDNA and anti-Ro/SSA antibodies both with a sensitivity of 20 % but with specificities of 98.7 % and 97.4 %, respectively. The sensitivities for the other autoantibodies varied between 14.3 % and 2.9 % at 98 % to 100 % specificity. In sera of unaffected controls antibody titers ranged between 6.7 % and 0 %.
The first antibody seen in the preclinical phase was anti-Ro/SSA; anti-RNP and anti-histone also appeared very early. Anti-centromere B and anti-Sm were detected on the verge of disease onset. In general, the number of patients expressing autoantibodies as well as the number of autoantibodies increased while approaching the date of disease manifestation.
Patients presenting with serositis as the first symptom had more autoantibodies and a shorter period between the positive blood sample and disease onset, indicating that severe symptoms at disease onset may be related to faster disease development.
The limited number of patients with pre-symptomatic blood tests certainly is a drawback of the present study. However, the results support the role of these autoantibodies in the first steps of the pathogenic process leading to the full-blown clinical picture of SLE. Analysis of autoantibody profiles in the preclinical phase of disease development may therefore contribute to improved diagnosis and clinical management of patients with SLE.