Membranous nephropathy associated with type 1 autoimmune pancreatitis and dominant glomerular IgG4 deposit

Abstract

We report a case of membranous nephropathy associated with type 1 autoimmune pancreatitis. A 58-year-old man presented with anorexia. Work-up revealed a mass in the pancreatic head, which was subsequently resected. Pathological examination showed diffuse infiltration of immunoglobulin (Ig) G4-positive plasma cells, which was compatible with the diagnosis of type 1 autoimmune pancreatitis. Serum IgG4 was elevated. He developed nephrotic syndrome around the time of the surgery. Kidney biopsy confirmed the diagnosis of membranous nephropathy. Immunofluorescent staining showed predominant glomerular IgG4 deposit among IgG subclasses. Tubulointerstitial nephritis, which is usually a dominant feature of renal involvement in IgG4-related disease, was not observed. The patient was treated with prednisolone and several immunosuppressants. During the course, the degree of proteinuria was associated with the serum IgG4 level. Serum antibody against phospholipase A2 receptor was negative. These findings together with IgG4-dominant glomerular deposit suggest that IgG4 may play a unique role in the pathogenesis of secondary membranous nephropathy caused by IgG4-related diseases.

A Refractory Case of Secondary Membranous Nephropathy Concurrent with IgG4-related Tubulointerstitial Nephritis

“…In contrast, anti-PLA2R antibodies do not play a principal role in the pathogenesis of IgG4-RKD ( 15 ). Serum anti-PLA2R antibodies and the immunostaining for PLA2R on histology were negative in all reported cases ( 7 , 9 - 12 ), suggesting that negative results of serum anti-PLA2R antibodies and the negative immunostaining for PLA2R may contribute to the diagnosis of secondary MN concurrent with IgG4-RD. Although the prevalence of anti-PLA2R antibodies in Japanese patients is lower than in patients from other countries, no Japanese patients with secondary MN have been positive for anti-PLA2R antibodies ( 16 ).…”

“…Regarding secondary MN concurrent with IgG4-RD, previous reports have revealed several patterns of dominant deposition of IgG-subclasses on glomeruli ( Table ). Five cases showed the dominant deposition of IgG4 on glomeruli, while the other three showed the deposition of various IgG-subclasses, including IgG1, IgG2, and IgG3 ( 7 , 9 - 12 ). These findings indicate that the dominant deposition of IgG-subclass is not totally diagnostic for secondary MN concurrent with IgG4-RD ( Table ).…”

Remission Induction of IgG4-related Membranous Nephropathy with Multitarget Therapy

“…All patients with IgG4-related MN whose sera were assayed showed marked elevations of their serum IgG4 concentrations, highlighting IgG4-related MN as an etiological form of secondary MN of IgG4-RD, distinct from the more typically recognized cellular inflammatory IgG4-RD processes ( 1 ). Furthermore, a previous case revealed the association of serum IgG4 levels and the degree of proteinuria due to IgG4-related MN ( 6 ). In the present case, the striking elevation of serum IgG4 to 1,650 mg/dL and the presence of nephrotic-range proteinuria may support the possibility of IgG4-related MN.…”

PLA2R-Negative Membranous Nephropathy Presenting as a Prodrome of IgG4-Related Autoimmune Pancreatitis

“…In secondary forms of MN, such IgG4 antibodies are absent or less prevalent [16], with the exception (by definition) of MN in the context of IgG4-RD. When IgG4-RD is diagnosed upon other organ(s) involvement, then suspicion should be raised that MN might be part of this syndrome, as rare cases of primary MN have been described in the context of IgG4-RD [17, 18, 19, 20]. The differential diagnosis between primary and secondary MN in a patient with known IgG4-RD is mainly based on the presence or absence of other markers, such as PLA2R.…”