Possible IgG4-Related Kidney Disease Requiring a Differential Diagnosis of Membranous Lupus Nephritis

Abstract

A 25-year-old woman presented with fever, arthralgia and proteinuria exhibiting leukopenia, hypocomplementemia, increased serum IgG and IgG4, and positive antinuclear and anti-double-stranded DNA antibodies. Renal biopsy revealed membranous nephropathy with tubulointerstitial nephritis. IgG subclass immunofluorescence revealed intense IgG4 expression in glomeruli, but no expression of IgG2. Observations resembled membranous lupus nephritis with tubulointerstitial nephritis; however, elevated IgG4, low titers of antinuclear and anti-double-stranded DNA antibodies, IgG4-bearing cell infiltration, and characteristic IgG subclass deposition in glomeruli prompted diagnosis of IgG4-related tubulointerstitial nephritis with membranous nephropathy. It is challenging but important to distinguish lupus nephritis from IgG4-related kidney disease.

An Overlapping Case of Lupus Nephritis and IgG4-Related Kidney Disease

“…This possibility is further supported by the findings of IgG4+ plasma cells in the interstitium, despite the normal serum IgG4 level. A similar report was published in the literature describing a “possible” IgG4-TIN concomitant with membranous nephropathy, where the absence of “definite” diagnosis was attributed to the difficulty differentiating findings from membranous lupus nephritis with severe tubulointerstitial changes [ 42 ]. Our case confirms the numerous clinical and histopathological similarities between LN and IgG4-RKD, and raises the possibility of an overlap syndrome.…”

Relationship between urinary protein changes in lupus nephritis and renal pathology

“…Urinary protein content is closely related with renal tubule pathological changes; increase in the urinary protein content is associated with a higher degree of renal tubular damage (Hiraki et al, 2012). This may be because renal tubules release lysosomes and complement protein after reabsorbing protein, while infiltrated renal tubular interstitial cells and inflammatory cells lead to renal tubular atrophy and mesenchymal transition (Jaybhaye et al, 2011;Romick-Rosendale et al, 2011;Singh et al, 2012;Takasaki, 2012;Yahata et al, 2012).…”

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

“…As far as we know, in the literature concerning MN associated with IgG4-RD, only 2 cases were without TIN [9, 10], and in one of them, IgG4 deposit was seen in the tubular basement membrane, suggesting some tubular involvement [10]. In 7 cases examined with immunofluorescence staining for IgG subclasses, IgG4 staining was dominant in glomeruli in 4 [10, 21–23], IgG2 and IgG3 were dominant in 2 cases [9, 18], and no glomerular staining was seen in one case [19]. IgG4 staining was also observed in plasma cells in the interstitium [17, 21–23] or tubular basement membrane [10], except for one case [9].…”

“…In 7 cases examined with immunofluorescence staining for IgG subclasses, IgG4 staining was dominant in glomeruli in 4 [10, 21–23], IgG2 and IgG3 were dominant in 2 cases [9, 18], and no glomerular staining was seen in one case [19]. IgG4 staining was also observed in plasma cells in the interstitium [17, 21–23] or tubular basement membrane [10], except for one case [9]. Our case was not associated with TIN and IgG4-dominant staining was seen only in the glomeruli, not in the interstitium.…”