Background Primary Sjögren’s Syndrome (pSS) is a chronic autoimmune disease. Symptoms range from sicca to systemic, potentially life-threatening organ damage. Little is known about the onset of the disease. Anti-Ro antibodies are described to develop years before the first symptoms. In addition, first degree relatives of pSS patients have an 11- to 19- fold increased risk of developing pSS themselves.

Objectives To identify and follow-up individuals at risk for pSS in order to study symptoms and immune pathology before and at development of pSS.

Methods In this ongoing long-term study individuals at risk for developing pSS but not fulfilling the ACR-EULAR classification criteria of pSS were included, defined as: 1.) Anti-SSA positive individuals (Anti-SSA⁺) without any sicca symptoms or diagnosis of an underlying systemic autoimmune disease; 2.) First degree relatives of patients (relatives) with an established diagnosis of pSS and typical autoantibodies (ANA ≥ 1:160 and/or anti-SSA⁺ and/or rheumatoid factor⁺); 3.) Individuals with at least one feature of the ACR-EULAR classification criteria for pSS, but not fulfilling the criteria (incomplete).

At baseline and at annual visits, demographic data, blood, saliva and urine samples were collected and stored. Salivary and lacrimal flow, salivary gland ultrasonography (SGUS), and patient-related outcome measures were analysed. A lip salivary gland biopsy was performed at baseline and upon development of symptoms suggestive of pSS. The primary endpoint was the development of definite pSS according to the ACR-EULAR classification criteria.

Results After the first year of recruitment, 50 individuals (Anti-SSA⁺ n=27, relatives n=21, incomplete n=2) were screened at baseline, of whom 28 were identified as individuals at risk for pSS and were included in the study. Twenty-two individuals were excluded from the study, most of whom were “relatives” with negative autoantibodies. Of these 28 individuals at risk, 89% were female (n=25), they had a median age of 53 years (IQR: 19) and 57% (n=16) had positive antinuclear antibodies. 86 percent were positive for anti-SSA and 14% were positive for anti-SSB. Decreased complement C3 and C4 were found in 18% and 4%, respectively. Serum IgG concentration was elevated in 29% of individuals. A reduction of lacrimal flow was found in 29% and stimulated whole salivary flow was reduced in 29%. The median of the ESSPRI was 1.6 (3.0). Eight-teen percent of the investigated individuals had a pathological ultrasound [Hocevar score median 4,5 (9,0)] and in 9% a focus score ≥ 1 [median 0.15 (0.57)] was found in the lip salivary gland biopsies. Four patients (14%) met the primary endpoint and were diagnosed with pSS within the first year.

Conclusion The design of the PRESTIGE study allows us to follow individuals at risk for pSS and will help to unveil symptoms and immune pathology as pSS develops. We suggest to establish a larger international pre-pSS cohort to increase statistical power.

Disclosure of Interests None declared