35.4.2. Primary Sjögren’s syndrome

Chapter 35

Gottenberg et al. [770] evaluated sFLC measurements in 139 patients with primary Sjögren’s syndrome (pSS), an autoimmune condition that typically affects lacrimal and salivary exocrine glands. A total of 22% of patients had raised sFLC concentrations, and mean levels were significantly higher than controls (p<0.001) (Figure 35.6.). sFLC concentrations were significantly correlated with IgG (p<0.001), rheumatoid factor (p<0.005), β2-microglobulin (p<0.001) and B-cell activating factor (BAFF, p<0.01). Association of elevated sFLCs with β2-microglobulin, gammaglobulin and lymphopenia was also reported for a mixed group of 22 patients with primary or secondary Sjögren’s syndrome [771]. In Gottenberg’s study [770], mean sFLC concentrations were higher in patients with autoantibodies, particularly when both anti-SSA and anti-SSB antibodies were present (Figure 35.7). In addition, patients with extra-glandular involvement had higher levels of sFLCs than those with glandular involvement alone. These results suggest that extra-glandular involvement in pSS is associated with more intense stimulation of B-cells.

pSS is associated with an increased risk of non-Hodgkin lymphoma (particularly mucosa-associated lymphoid tissue (MALT) lymphoma) with an odds ratio of 12.9 [772]. In a cohort of 395 patients enrolled into a 5-year prospective study (the ASSESS biobank), Gottenberg et al. [770] sought to discover whether sFLC measurements could identify pSS patients at increased risk of lymphoma. At enrolment, a total of 16/395 patients had a history of lymphoma; median serum concentrations of BAFF and β2-microglobulin were significantly higher in these patients but sFLC concentrations and ratios were normal. Data from the follow-up of this cohort has yet to be released.

There has been increasing interest in the role of BAFF as a marker of disease activity and as a potential therapeutic target in pSS. In a phase 2 trial of belimumab (a monoclonal antibody against BAFF), in which sFLC measurements were included as part of the haematological assessment, significant reductions in sFLC concentrations were observed following treatment [773].