Background/Purpose:

The association between germinal center (GC)-like structures and lymphoma in primary Sjögren’s syndrome (pSS) has been demonstrated recently (1). Here we present a comprehensive analysis of associations between these GC-like structures in minor salivary glands and other disease characteristics.

Methods:

One-hundred-and-sixty biopsies from pSS patients fulfilling the 2002 AECG criteria were evaluated by re-examining the original diagnostic minor salivary gland biopsies for the presence of ectopic lymphoid structures, defined as a densely packed dark zone and a less densely packed light zone in association with focal sialadenitis in otherwise normal glands. Demographic and disease characteristics were extracted from the Malmö pSS database. T-test and Χ²statistics were applied as appropriate.

Results:

Thirty-eight (23.8%) of 160 biopsies were GC-positive, with similar frequency in both genders. Age at diagnosis was slightly lower in GC-positive patients (48.3(12.9) vs 53.8(12.8) yrs respectively, ns. The frequency of anti-SSA/SSB antibodies was significantly higher in GC-positives (79% vs 61%, p=0.045), with a trend towards higher prevalence of RF. ANA frequency was similar. During follow-up systemic manifestations were reported cumulatively in 71% of GC-positive and 49% of GC-negative patients (p=0.019). The presence of additional autoimmune phenomena (presence of either autoimmune diseases such as thyroiditis, celiac disease, primary biliary cirrhosis, etc, or additional autoantibodies such as centromere, anti-DNA, anti-cardiolipin, anti-thyroid, etc, was overrepresented in GC-positives (50% vs 27%, p=0.011). As expected, GC- formation was associated with lymphoma development (12% vs <1%, p=0.011). There were no significant differences between GC-positive and GC-negative patients with regard to complement levels, IgG levels, or ESR.

Stimulated sialometry was significantly lower in patients with GC-like structures (2.40 (2.33) vs 3.39 (3.29) ml/5 min, p=0.013). Ultrasonography of major salivary glands demonstrated more often pSS typical hypoechoic lesions in those with GC-like structures (67% vs 35%, p=0.012) . Other exocrine function tests such as unstimulated whole sialometry, Schirmer test and van Bijsterveld score resulted in trends towards more severe disease in GC-positives. No difference was demonstrated regarding subjective dryness.

Conclusion:

Beyond being a strong predictor of lymphoma development, GC-like structures in minor salivary glands predict systemic disease manifestations and worse exocrine performance as well as higher grade of morphological destruction assessed by ultrasonography. The simultaneous presence of additional autoimmune phenomena may be a marker of general GC-formation not restricted to the salivary glands and thus characterize a separate pSS phenotype with potentially severe and complicated disease.

1. Theander E et al. Ann Rheum Dis 2011;70:1363-8.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-importance-of-germinal-center-like-structures-in-primary-sjogrens-syndrome-salivary-glands-beyond-lymphoma-risk/