Sjögren's syndrome complicated with membranous nephropathy, a cause or coincidence?

Sjögren's syndrome (SS) has been a well-documented cause of secondary membranous nephropathy (MN); however, the prevalence is quite low. Since primary MN is also a common disease in middle age, whether MN is secondary to SS or just coincidence remains uncertain. The detection of phospholipase A2 receptor (PLA2R), which is most often positive in idiopathic MN, has been rarely reported in such cases. We retrospectively studied 13 cases diagnosed with MN and SS in Huashan Hospital between 2009 and 2020, and performed PLA2R detection. We also review the literature by searching in the PubMed database. Among the 13 patients, 8 were found to be PLA2R-positive and 5 were negative. Nine patients were female. All but 1 patients had normal renal function at the time of biopsy. All patients showed positive anti-nuclear antibody and anti-SSA. Two of the 8 PLA2R-positive patients showed positive anti-SSB and 1/8 had mild hypocomplementemia, while all 5 PLA2R-negative patients had positive anti-SSB and 3 showed hypocomplementemia. Renal biopsy revealed focal MN and markedly mesangial hyperplasia in PLA2R-negative patients. Mesangial electron deposits were observed in 1 PLA2R-positive patient in small amounts, and in 3 PLA2R-negative patients with 2 in large amounts. During follow-up, 2 patients in the PLA2R-negative group presented with progressively decreasing serum complement levels, and another one was diagnosed with systemic lupus erythematosus (SLE). In patients with both MN and SS, PLA2R-negative MN should be considered as a secondary form. Careful screen for SLE is necessary in these patients during follow-up.