Hypergammaglobulinaemia predicts glandular and extra-glandular damage in primary Sjögren's syndrome: results from the KISS cohort study

Objective. To investigate whether temporal changes in immunoglobulin (Ig) levels and persistent hypergammaglobulinaemia cause glandular and extraglandular damage in patients with primary Sjgren's syndrome (pSS). Methods. Cumulative demographics and clinical and serological data from pSS patients in the Korean Initiative pSS cohort were evaluated. Persistent hypergammaglobulinaemia was defined as mean IgG levels of 1600 mg/ dL over 3 years. Salivary gland damage was assessed by measuring salivary flow impairment, and lacrimal gland damage was assessed by examining ocular structural abnormalities. Solid organ damage included neurological and pleuropulmonary damage, renal impairment and lymphoproliferative disease. Independent predictors of glandular and extra-glandular damage in the third year were identified by logistic regression. Results. Of 256 patients with pSS (median age, 55 years; 98% female), 47% had hypergammaglobulinaemia at baseline. IgG levels fell during the first 2 years in patients with hypergammaglobulinaemia at baseline, but not in those with normal IgG levels. Changes in IgG levels were associated with hydroxychloroquine and glucocorticoids. In the third year of follow-up, salivary flow impairment and solid organ damage were present in 71% and 9% of patients, respectively. After adjusting for age and medication use, persistent hypergammaglobulinaemia was associated with salivary flow impairment and solid organ damage in the third year. Patients in whom IgG fell by more than 80 mg/dL from baseline over 2 years showed less solid organ damage. Conclusion. Persistent hypergammaglobulinaemia was associated with salivary gland and solid organ damage. Decreased IgG may attenuate progression to solid organ dysfunction.