To our knowledge, we report the first case of a patient who was diagnosed with primary APS associated with APS chronic vascular nephropathy and MN with anti-PLA2R antibodies without any features of lupus MN.
The etiology of this association is unclear. One hypothesis is that antibodies appear against a dysimmunitary background and generate a multisystem autoimmune syndrome. For example, Stehlé et al.  showed, in 9 patients who had MN and sarcoidosis, that all patients with active sarcoidosis had PLA2R antigen in deposits, while none of those with inactive sarcoidosis had detectable PLA2R in biopsy. The diagnosis of sarcoidosis could precede the diagnosis of MN by several years. In 2 cases, sarcoidosis activity was linked to the evolution of serum PLA2R antibody levels and proteinuria. Therefore, they hypothesized that there was a causal link between the two diseases and that the immunological setting of sarcoidosis might trigger immunization against PLA2R. Thus we might also ask if the immunological setting of APS might trigger immunization against PLA2R. In our case the APS was quiescent under treatment in recent years but the antiphospholipid antibodies (lupus anticoagulant) were positive at the onset of nephrotic syndrome. Three months after the onset of nephrotic syndrome (prior to treatment with rituximab) these antibodies spontaneously became negative, and partial remission as well as a decrease in serum PLA2R antibody levels occurred 12 months later. Partial remission of the nephrotic syndrome and decrease in serum PLA2R antibody levels could therefore be related to the lack of APS immunological activity.
Another hypothesis is that MN is the first event of SLE, which is one of the main etiologies of secondary APS. Indeed, Sinico and co-workers  studied the prevalence and clinicopathologic features of renal involvement in 160 patients with primary APS. Renal involvement was observed in 14/160 (9%), of whom 4/14 patients (28.5%) suffered from MN with atypical features usually related to lupus MN (mesangial proliferation, mesangial and/or subendothelilal deposits, C1q deposits and IgA deposits). Regrettably, PLA2R antibody assay was not reported. Despite a long follow-up (6.9 up to 14.1 years), none developed full-blown lupus. It should be noted that these patients were treated with steroids (plus cyclophosphamide in 2 patients) because of renal disease, and this could have prevented other lupus manifestations from occurring. As MN with atypical features may precede the clinical and biologic manifestations of SLE, these patients could eventually develop SLE and need long-term follow-up. However, in our observation, the presence of anti-PLA2R antibodies and PLA2R in deposits makes the diagnosis of lupus MN unlikely and no sign of SLE was observed after 4 years of follow-up.
Finally, a fortuitous association cannot be eliminated.
In our patient’s case, the presence of anti-PLA2R antibodies motivated the use of rituximab, which may explain the partial remission of the nephrotic syndrome. Our patient’s prognosis is probably worse than PLA2R-related MN without primary APS due to the presence of antiphospholipid syndrome chronic vascular nephropathy with advanced chronic vascular lesions.
To conclude, we observed the first association between primary APS and PLA2R-related MN. Our observations could suggest a causal link between primary antiphospholipid syndrome and PLA2R-related MN. Consequently, it would be interesting to screen for anti-PLA2R in further cases of nephrotic syndrome in patients with APS and to search APS antibodies in all MN.