Differential Expression of C4d and IgG4 Immunohistochemical Markers in Lupus and Non-Lupus Membrabous Glomerulonephritis
Umer N Sheikh, Sajid Farooq, Paul J Kowalski, Hong Qu. St. John Hospital & Medical Center, Detroit, MI; Good Samaritan Hospital, Cincinnati, OH
Background: Systemic lupus erythematosus membranous glomerulonephritis (SLE-MGN) is sometimes difficult to distinguish from non-lupus membranous glomerulonephritis (NL-MGN) and represents about 20% of clinically significant renal disease in SLE. By Light Microscopy (LM), membranous lesions of SLE-MGN without superimposed proliferative GN are often indistinguishable from NL-MGN. Unlike in NL-MGN, immune complex deposits (ICDs) in SLE-MGN are not restricted to glomerular basement membrane (GBM) and may also be found in the mesangium, tubular basement membrane (TBM), and vasculature/interstitium (V/I). The study aims to review differential expression of two immunohistochemical markers (IHC), namely C4d and IgG4, in SLE-MGN and NL-MGN.
Design: 27 patients between 2006-2012 were retrospectively reviewed. Out of these, 15 patients (age ranges from 21-51 years; all females) had SLE-MGN and 12 patients (age ranges from 19-74 years with M:F ratio 6:5) had NL-MGN (including idiopathic and secondary MGN). At the time of diagnosis, all SLE-MGN patients had extra-renal manifestations of SLE and positive serology. Nephrotic range proteinuria was present in all 27 patients. All renal biopsies were studied by routine LM, electron microscopy (EM) and immunofluorescence (IF), with IHCs performed for C4d and IgG4 for the localization of ICDs in the GBM, mesangium, TBM, and V/I.
Results: Both SLE-MGN and NL-MGN were similar in terms of morphology, showing membranous pattern of glomerular involvement, with thickening of the peripheral capillary loops, and basement membrane spikes and vacuoles. The results of IHCs are shown in the table. In 3/15, 5/15, and 7/15 of SLE-MGN cases (but no NL-MGN), granular staining for C4d was noted in the mesangium, TBM, and V/I, respectively. Of note, GBM IgG4 deposition was almost exclusively prevalent in NL-MGN (100%), in contrast to SLE-MGN (7%).
Conclusions: IgG4 staining may aid in distinguishing NL-MGN from SLE-MGN in some cases where the diagnosis of SLE is equivocal. Additionally, C4d highlights the GBM ICDs in both SLE-MGN and NL-MGN. However, C4d-positive granular staining in TBM and vascular wall is almost only seen in SLE-MGN, also aiding to separate SLE-MGN from NL-MGN. Future studies to include a larger cohort are suggested to verify these results.
|GBM||15/15 (100%)||1/15 (7 %)||12/12 (100%)||12/12 (100%)|
|Mesangium||3/15 (20%)||1/15 (7 %)||0/12 (0%)||0/12 (0%)|
|TBM||5/15 (33%)||0/15 (0%)||0/12 (0%)||0/12 (0%)|
|V/I||7/15 (47%)||0/15 (0%)||0/12 (0%)||0/12 (0%)|