Modern pathology – thsd7a staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity

Thrombospondin type I domain-containing 7A (THSD7A) is a known antigenic target of autoantibodies leading to primary membranous glomerulopathy and was reported to account for ~10 % of phospholipase A2 receptor (PLA2R)-negative membranous glomerulopathy. Gas in babies that breastfeed It has been proposed that PLA2R and THSD7A autoantibodies are mutually exclusive in membranous glomerulopathy. Gas unlimited houston We validated an immunohistochemical assay to investigate for THSD7A-associated membranous glomerulopathy and utilized it in 258 consecutive native kidney biopsies, which showed membranous glomerulopathy in our laboratory, with the exception of membranous lupus nephritis. Gas tax Membranous glomerulopathy stained positive for THSD7A-only in 7 (3 %) cases, PLA2R-only in 141 (55 %) cases, and showed dual positivity for THSD7A and PLA2R in 2 (1 %) cases. Gas 10 8 schlauchadapter Serologic testing for antibodies to PLA2R and THSD7A was performed in a subset of these patients. Electricity rate per kwh philippines There was 100 % correlation between positive THSD7A and /or PLA2R tissue staining and the presence of the corresponding autoantibodies in the serum including the two cases with dual positive THSD7A and PLA2R antibodies. Electricity in costa rica current We describe and provide a protocol for detection of THSD7A-associated membranous glomerulopathy in clinical practice. Electricity and magnetism worksheets The cases with dual THSD7A and PLA2R positivity show that these autoantibodies are not mutually exclusive. Electricity in the body symptoms They also emphasize the importance of using a panel-based approach when subtyping membranous glomerulopathy as a patient could conceptually be identified and treated based on anti-PLA2R titers, but still have anti-THSD7A antibodies driving persistent disease.

We sought to validate a staining technique for the detection of THSD7A-associated membranous glomerulopathy on kidney biopsies. Electricity song 2015 An immunoperoxidase staining method was utilized as our initial attempt using an indirect immunofluorescence technique, similar to that described for PLA2R, 10 showed false negative staining. Electricity orlando Since THSD7A is normally present in podocytes, the aim was to optimize the method such that we had minimal THSD7A staining in normal glomeruli and non-THSD7A membranous glomerulopathy while maintaining strong positive staining in THSD7A-associated membranous glomerulopathy. Electricity n and l Weak pseudo-linear staining along the glomerular basement membranes was commonly present under normal conditions and in non-THSD7A-associated membranous glomerulopathy. Electricity out However, strong diffuse global granular staining of THSD7A along the capillary loops was only present in the THSD7A-associated membranous glomerulopathy cases ( Figure 1).

Membranous glomerulopathy stained positive for THSD7A-only in 7 (3 %) cases, PLA2R-only in 141 (55 %) cases, and showed dual positivity for THSD7A and PLA2R in 2 (1 %) cases ( Figure 2). 1 unit electricity cost in bangalore Staining was negative for both in 108 (42 %) cases. Electricity outage austin A summary of the clinical findings for the nine patients with THSD7A-positive membranous glomerulopathy is available in Table 1. Gas kinetic energy formula They had a mean age of 62 years and a mean of 8.2 g of proteinuria per day. A level physics electricity equations Serologic tests for ANA, ANCA, HBV, HCV, and HIV as well as complement levels were normal in all of these patients. Electricity worksheets for 4th grade One of the patients had a remote history of membranous glomerulopathy that was in clinical remission for 7 years prior to the current biopsy. Gas out game instructions Tissue from the previous biopsy was not available for examination.

The diagnosis of membranous glomerulopathy is made when the renal biopsy shows a combination of granular deposits of IgG along the glomerular basement membranes on immunofluorescence in combination with subepithelial deposits by electron microscopy. Gas density Traditionally, this disease has been divided into primary, in which the etiology is unknown, and secondary when one of numerous associated conditions is identified. Types of electricity Identification of PLA2R as the antigenic target in ~70 % of primary membranous glomerulopathy has made it possible to diagnose a specific subtype of membranous glomerulopathy based on the underlying pathogenic mechanism driving the disease and has enabled non-invasive monitoring utilizing serologic testing for PLA2R antibodies as biomarkers of activity. Electricity merit badge pamphlet pdf 4, 5 The recent identification of THSD7A as a second antigenic target of antibodies leading to primary membranous glomerulopathy provides the ability to classify more of these cases. Electricity jeopardy We provide here our experience with detecting THSD7A-associated membranous glomerulopathy on renal biopsy using a specific immunohistochemical stain in a large biopsy cohort.

Subclassifying membranous glomerulopathy based on the autoantibody driving the disease can be performed through serologic testing for autoantibodies or staining the renal biopsy. Electricity static electricity In the setting of PLA2R, tissue staining has been shown to be more sensitive for the detection of the type of membranous glomerulopathy present than serum testing. Gas density units 11 Care must be taken when utilizing an immunoperoxidase technique for membranous subtyping to avoid mistaking normal podocyte staining for evidence of disease-associated positivity in glomeruli ( Figure 1). Electricity explained We have found that for THSD7A, a diffuse global capillary wall staining pattern for THSD7A is specific for identifying cases in which the patients have autoantibodies directed against this protein. Electricity png The protocol utilized in our laboratory is provided in Table 3. Static electricity sound effect However, careful validation must be performed in each laboratory as variability in local tissue processing protocols (eg, fixation type and time) might affect these results and alterations in the protocol will likely be necessary to achieve acceptable results.

We present here the first report of cases of membranous glomerulopathy with dual positive antibodies against THSD7A and PLA2R. Hp gas kushaiguda These rare cases with dual THSD7A and PLA2R positivity show that these autoantibodies are not mutually exclusive and reveal the need for further study to determine the underlying etiology when more than one antibody is present. Gas natural We do not know at this time if both autoantibodies are pathogenic in driving disease. Gas what i smoke It is possible that one of the autoantibodies represents ‘opportunistic’ antibody formation after podocyte antigens are exposed in disease. La gas prices Alternatively, as genetic association studies have shown that the genetic susceptibility to idiopathic membranous glomerulopathy involves HLA DQA1, 12, 13 it is possible that certain individual’s immune systems are genetically primed to produce autoantibodies to podocyte antigens and both are pathogenic.

The diagnosis and treatment of membranous glomerulopathy is in the midst of transformation as details concerning the underlying pathogenic drivers of disease are uncovered. Gas in back We present here our experience with THSD7A staining of renal biopsies in clinical practice. Dynamic electricity examples Further work is needed to determine whether or not serologic studies for THSD7A are useful for noninvasive monitoring of disease activity as they are for PLA2R. Gas 78 industries Unlike previous reports, we show that THSD7A and PLA2R autoantibodies do rarely occur together in cases of membranous glomerulopathy. I feel electricity in my body These cases emphasize the importance of using a panel-based approach when subtyping membranous glomerulopathy as a patient could conceptually be identified and treated based on anti-PLA2R titers, but still have anti-THSD7A antibodies driving persistent disease.