Weakened IgG4 Staining and Positive PLA2R staining Indicate Resolving Primary Membranous Glomerulopathy (MGN)

Introduction/Objective IgG4 related disease, a systemic autoimmune inflammatory disorders, can be identified by high% of IgG4 positive plasma cells, thus IgG4 staining in paraffin embedded tissue is widely available in the most of pathology labs. IgG4 staining has been found useful to identify primary MGN (PLA2R and/or THSD7A positive) by others and us. This study was to scrutinize the findings of primary vs secondary MGN needed for IgG4 staining as a screening tool in our renal pathology practice over pasts 5 years Methods/Case Report IgG4 staining in paraffin embedded tissue was performed in 45 primary MGN and 43 secondary MGN after the clinical history was reviewed and a possibility of primary MGN cannot be excluded. In addition, both groups of cases were also stained for PLA2R. Detail correlation with clinical history was analyzed. Results (if a Case Study enter NA) Totally 82 % (37/45) of primary MGN was found diffuse positive for IgG4 staining at 2+ intensity in the glomeruli. Seven out of eight remaining primary MGN cases with either negative or weak IgG4 stained MGN were found to have diffuse resolving features by electron microscopy but there was still positive PLA2R staining in the glomeruli. All secondary MGN were stained negatively for both IgG4 and PLA2R and we found that etiologies of the secondary MGN included membranous lupus nephritis, infection, GVHD, or variants of cancers. Conclusion Our data indicate that IgG4 staining along (without IgG1-3 staining) is a reliable screening tool to confirm the majority of primary MGN vs secondary MGN in paraffin embedded tissue. As both PLA2R+ and THSD7A+ primary MGN are both IgG4 related, the IgG4 staining may potentially represent a wider range of scope in identifying primary MGN. In addition, negative/weak IgG4 staining in PLA2R-positive MGN most likely represents a primary MGN with resolving features.

Rare presentation of primary hepatic marginal zone B-cell lymphoma and membranous glomerulopathy in a 3-year-old boy

Introduction/Objective Primary hepatic marginal zone B-cell lymphoma (MZL) is a rare entity that has been described with chronic inflammatory disorders such as chronic viral hepatitides B and C and primary biliary cholangitis. We report MZL in a 3-year-old African-American boy that was discovered incidentally at autopsy. Methods/Case Report The patient first came to medical attention at 9-months of age with bilateral periorbital edema that progressed to generalized edema of the[PL1] face, extremities, and abdomen. Laboratory testing showed nephrotic syndrome with massive proteinuria (50-60 g/day). A percutaneous renal biopsy specimen showed membranous glomerulopathy with PLA2R detected by immunofluorescence, and granular IgG deposition along tubular basement membranes. Serum was negative for anti-PLA2R antibodies. The patient suffered recurrent upper respiratory tract infections requiring several intensive care hospitalizations. At 3 years of age, he was transported unresponsive and pulseless to the emergency department where he was pronounced dead. A brother with the infantile nephrotic syndrome had died from sepsis at 2 years of age. Suspicion of abuse led to an autopsy by the medical examiner, who discovered nodular masses in the right and left liver lobes, which histologically showed a serpiginous infiltrate of small B-lymphocytes positive for CD20, CD43 admixed with plasmacytoid cells with kappa light chain restriction. There were no extrahepatic tumors. Transmission electron microscopy of glomeruli showed membranous glomerulopathy. Kidneys showed dense reactive interstitial lymphocytic infiltrate with germinal centers Results (if a Case Study enter NA) NA Conclusion To our knowledge, this is the first reported case of MZL presenting in a pediatric patient with membranous glomerulopathy. Both diagnoses are associated with autoimmune diseases and persistent, chronic inflammation. Recurrent infections in this patient suggest an immunoregulatory disorder, setting the stage for chronic inflammation, as seen in the kidney, with progression to MZL in the liver.

Immunohistochemical Expression of FOXP3+ Regulatory T Cells in Proteinuric Primary Glomerulopathies

FOXP3+ regulatory T-cell (Tregs) detection in renal allograft biopsies has been associated with a less intense immune response. Data about FOXP3+ Tregs’ presence and role in primary glomerulopathies of native kidneys are minimal. We comparatively studied the immunohistochemical expression of FOXP3+ Tregs, CD4+ and CD3+ T cells in IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), and membranous glomerulopathy (MGN). We retrospectively reviewed 71 renal biopsies (28 from patients with IgAN, 22 from patients with FSGS and 21 from patients with MGN) performed with proteinuria as the main indication. FOXP3+ Tregs and CD4+ and CD3+ T cells in inflammatory cell infiltrates of the interstitial tissue and periglomerular space were automatically counted using image analysis software. Univariable and multivariable logistic regressions were applied for statistical analysis. Nuclear FOXP3+ immunohistochemical expression was observed in T cells in 64% of IgAN cases, 77% of FSGS cases, and 76% of MGN cases ( p > 0.05 ). Absolute FOXP3+ Tregs count in the interstitial tissue was higher in patients without arteriolar hyalinosis than in those with arteriolar hyalinosis (1.814 ± 2.160 vs. 831 ± 696; p = 0.029 ). In patients with a high FOXP3+/CD4+ ratio in the interstitial tissue, the odds ratio for CKD-EPI eGFR ≥60 ml/min/1.73 m2 at biopsy was 4.80 (95% CI: 1.29–17.91; p = 0.019 ). FOXP3+ Tregs intrarenal infiltration in primary glomerulopathies is common. FOXP3+ Tregs’ increased expression may be associated with milder histological lesions. High FOXP3+/CD4+ ratio in the interstitial tissue may have prognostic significance for renal function preservation.