Elevated serum gamma globulin or low complement levels in patients with symptoms of Sjögren’s syndrome (SS) may predict their likelihood of progression to the autoimmune disease, according to findings from a longitudinal cohort study.
“Identification of serological variables that predict the development of Sjögren’s syndrome may contribute to earlier diagnosis and treatment of the disease and, ultimately, better long-term outcome,” Caroline H. Shiboski, DDS, PhD, chair of the department of orofacial sciences at the University of California, San Francisco, and her coauthors wrote.
The researchers described the results of a follow-up visit 2 years after baseline for 771 of 3,310 participants in the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry.
Approximately half of the participants did not meet either the 2012 American College of Rheumatology criteria or the 2016 ACR-European League Against Rheumatism criteria for Sjögren’s syndrome at baseline. At follow-up, 8% met the ACR criteria, and 9% met the ACR-EULAR criteria (Arthritis Care Res. 2017 April 24. doi: 10.1002/acr.23264).
For the other patients, those who did not progress according to either criteria, the researchers “observed remarkable stability over 2-3 years for both individual phenotypic features of SS and SS status, a finding consistent with smaller prospective studies with longer durations of follow-up.”
The participants with hypergammaglobulinemia at study entry, defined as immunoglobulin G greater than 1,445 mg/dL, were four times more likely to progress to full disease after 2 years (P = .006), while those with hypocomplementemia were six times more likely to progress (P = .004) than were those without. Hypocomplementemia was defined as C3 less than 90 mg/dL and/or C4 less than 16 mg/dL.
“However, the highest percentage of progression from not meeting the SS criteria at baseline to meeting them at the 2- to 3-year follow-up was among those who reported receiving immunomodulating/suppressive medications at both time points, both when using the ACR criteria (18% progressors) and the ACR-EULAR criteria (12% progressors),” the authors wrote.
In general, those with confirmed diagnosis at study entry showed reasonable stability in both individual phenotypic features and disease status.
Overall, 93% of participants who met the ACR criteria for SS at baseline still met those criteria at the 2- to 3-year follow-up, as did 89% of participants who met the ACR-EULAR criteria at baseline.
A majority of the participants who reverted from SS classification at baseline to failure to meet the criteria at follow-up had a change in labial salivary gland biopsy results. This occurred in 60% who met ACR criteria at baseline and 75% who met ACR-EULAR criteria at baseline.
More than 85% of participants in the study reported dry mouth or dry eyes, but participants with SS were much more likely to have positive anti-SSA, positive rheumatoid factor, antinuclear antibody titer of 1:320 or greater, hypergammaglobulinemia, and focal lymphocytic sialadenitis with a focus score of 1 or more focus per 4 mm2.
The researchers also reported a very low incidence (0.5%) of lymphoma among the participants available for follow-up.
The study was supported by the National Institutes of Health, the Jerome L. Greene Foundation, and the Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center. Six authors declared consultancies, honoraria, and grants from pharmaceutical companies.