Background Positive antinuclear antibodies (ANA) indicate vascular pathology or collagen diseases. However, the percentual distribution of diagnoses of patients with first-time determined ANA is not well defined. In addition, vascular abberation induces the overexpression of vascular adhesion molecules in these patients. The soluble serum isoforms of these molecules may thus serve as disease markers.
Objectives The aim of this study was to diagnose patients with first-time determined positive ANA and then further analyse clinical parameters, organ involvement and soluble vascular adhesion molecules as potential disease markers.
Methods Prospective observational study with 100 patients with first-time diagnosed positive ANA. Patients were diagnosed according to international criteria and were further characterized by routine and autoimmune serology, additional clinical parameters and organ involvement. Serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), endothelial-leukocyte adhesion molecule-1 (sELAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were analysed by ELISA at baseline, and in a subgroup after three, five and 10 months with immunosuppressive therapy. Adhesion molecule parameters were compared to age and gender-matched healthy controls.
Results ANA-positive patients included undifferentiated collagen diseases (UCD, n=30), ANA-positive arthritides (AA, n=20), systemic sclerosis (SSc, n=11), seropositive rheumatoid arthritis (RA, n=10), Sjögren's syndrome (SS, n=7), and other disorders such as multiple sclerosis or autoimmune hepatitis. Serum levels for sICAM-1 did not differ from healthy controls. sVCAM-1 (ng/ml) was significantly (p≤0.05) elevated in UCD (631±271 vs. 182±126), AA (612±252 vs. 185±83), RA (619±309 vs. 206±51), SSc (462±283 vs. 189±78), and SS (684.1±315 vs. 162±34). sELAM was also significantly elevated in SSc (5.5±2.0 vs. 3.1±2.3). Compared to controls, sVCAM levels decreased in all SSc patients undergoing immunosuppression (n=7) after three, five and 10 months from 504±337 (p=0,04) to 296±139 (p=0,1), 301±112 (p=0,06) and 201±103 (p=0,8), respectively. Also, sELAM first showed a decline from 5.1±2.14 (p=0,02) to 3.8±3.64 (p=0.4), 3.3±5.0 (p=0.7) but increased again after 10 months 5.8±4.3 (p=0.08), respectively. Baseline findings of clinical parameters (Health Assessment Questionaire: 0.71±0.59, modified Rodnan total skin score: 2.2±5.3, visual analogue pain scale: 50.9±26.5), serologic tests (ESR: 12.0±12,75 mm/h, CRP: 4.2±9.1 mg/dl) or clinical parameters (pulmonary diffusion capacity TLCO/VA: 86.9±23.4%, pulmonary arterial pressure determined by ECHO: 21.4±8.9 mmHg) did not change over time in these immunosuppressed patients.
Conclusions The majority of patients with first-time diagnosed positive ANA had UCD and AA/RA. 11% were identified as SSc. sVCAM appreared as a disease marker for arthritis, collagen disease or vasculitis at baseline and after immunosuppression in SSc. Further studies with more actively diseased patients such as pulmonary hypertension or renal involvement are needed.
Disclosure of Interest M. Oleszowsky Grant/research support from: Actelion, M. Seidel: None declared