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.). A number of other studies have also shown elevation of sFLC concentrations in primary Sjögren’s syndrome [771][1087][1088][1089][1142]. In the study by Gottenberg et al. [770], 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]. Gottenberg [770] also reported that 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.

A number of studies have investigated the correlation of sFLCs and other markers of B-cell activity with disease activity (as assessed by the EULAR Sjögren’s Syndrome Disease Activity Index, ESSDAI) [1087][1088][1089][1142]. sFLC levels were associated with ESSDAI score in all four studies, and James et al. [1088] found that sFLC levels were associated with the cutaneous, biological and renal domains of the ESSDAI in particular.

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. This finding was confirmed in their later publication [1087]. In a different study [1142], an abnormal κ/λ sFLC ratio was found in 11% (5/45) pSS patients at diagnosis, but 50% (6/12) of patients with established salivary gland MALT lymphoma without recent B-cell depletion therapy. Therefore, an abnormal κ/λ sFLC ratio was proposed as a potential biomarker of MALT lymphoma.

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].