CD11b suppresses TLR7-driven inflammatory signaling to protect against lupus nephritis.

Lupus Nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) that affects kidney function. Here, we investigated the role of CD11b, a protein encoded by the gene, in the development of LN and its functional activation as a therapeutic strategy. Genetic coding variants of significantly increase the risk for SLE and LN by producing a less active CD11b and leading to elevated levels of type I interferon (IFN I).

SeqStain is an efficient method for multiplexed, spatialomic profiling of human and murine tissues.

Spatial organization of molecules and cells in complex tissue microenvironments provides essential organizational cues in health and disease. A significant need exists for improved visualization of these spatial relationships. Here, we describe a multiplex immunofluorescence imaging method, termed SeqStain, that uses fluorescent-DNA-labeled antibodies for immunofluorescent staining and nuclease treatment for de-staining that allows selective enzymatic removal of the fluorescent signal.

Development and Validation of a Deep Learning Model to Quantify Interstitial Fibrosis and Tubular Atrophy From Kidney Ultrasonography Images.

Importance: Interstitial fibrosis and tubular atrophy (IFTA) is a strong indicator of decline in kidney function and is measured using histopathological assessment of kidney biopsy core. At present, a noninvasive test to assess IFTA is not available.

Objective: To develop and validate a deep learning (DL) algorithm to quantify IFTA from kidney ultrasonography images.

Interobserver reliability of methods to determine complete resection of adenomas in colonoscopy.

Background: Forceps margin biopsy and polypectomy specimen margins have both been used to assess for polypectomy resection adequacy. The interobserver reliability of the two methods has not been well described.

Methods: The interpretability of polypectomy specimens for presence of residual neoplasia at the margin was assessed by two blinded pathologists.

Positive Allosteric Modulation of CD11b as a Novel Therapeutic Strategy Against Lung Cancer.

Lung cancer is one of the leading causes of cancer-related deaths in the United States. A major hurdle for improved therapies is immune suppression mediated by the tumor and its microenvironment. The lung tumor microenvironment (TME) contains large numbers of tumor-associated macrophages (TAMs), which suppress the adaptive immune response, increase neo-vascularization of the tumor, and provide pro-tumor factors to promote tumor growth.

Urine exosomal ceruloplasmin: a potential early biomarker of underlying kidney disease.

Background: Previously we found that kidney tissue and urinary exosomes from patients of diabetic kidney disease showed high levels of ceruloplasmin (CP). Because CP is an acute-phase protein of kidney origin, it could be an early marker of many other kidney diseases. To investigate this hypothesis, we first measured urine exosomal and kidney expression of CP in non-diabetic chronic kidney disease (CKD) patients (membranous nephropathy, focal segmental glomerulosclerosis, lupus nephritis and IgA nephropathy) followed by a longitudinal study in rat passive Heymann nephritis (PHN), a model of human membranous nephropathy.

Nonimmune cell-derived ICOS ligand functions as a renoprotective αvβ3 integrin-selective antagonist.

Soluble urokinase receptor (suPAR) is a circulatory molecule that activates αvβ3 integrin on podocytes, causes foot process effacement, and contributes to proteinuric kidney disease. While active integrin can be targeted by antibodies and small molecules, endogenous inhibitors haven't been discovered yet. Here we report what we believe is a novel renoprotective role for the inducible costimulator ligand (ICOSL) in early kidney disease through its selective binding to podocyte αvβ3 integrin.

uPAR isoform 2 forms a dimer and induces severe kidney disease in mice.

Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived circulating signaling molecule that has been implicated in chronic kidney disease, such as focal segmental glomerulosclerosis (FSGS). Typically, native uPAR (isoform 1) translates to a 3-domain protein capable of binding and activating integrins, yet the function of additional isoforms generated by alternative splicing is unknown. Here, we characterized mouse uPAR isoform 2 (msuPAR2), encoding domain I and nearly one-half of domain II, as a dimer in solution, as revealed by 3D electron microscopy structural analysis.

CD11b activation suppresses TLR-dependent inflammation and autoimmunity in systemic lupus erythematosus.

Genetic variations in the ITGAM gene (encoding CD11b) strongly associate with risk for systemic lupus erythematosus (SLE). Here we have shown that 3 nonsynonymous ITGAM variants that produce defective CD11b associate with elevated levels of type I interferon (IFN-I) in lupus, suggesting a direct link between reduced CD11b activity and the chronically increased inflammatory status in patients. Treatment with the small-molecule CD11b agonist LA1 led to partial integrin activation, reduced IFN-I responses in WT but not CD11b-deficient mice, and protected lupus-prone MRL/Lpr mice from end-organ injury.

Absence of miR-146a in Podocytes Increases Risk of Diabetic Glomerulopathy via Up-regulation of ErbB4 and Notch-1.

Podocyte injury is an early event in diabetic kidney disease and is a hallmark of glomerulopathy. MicroRNA-146a (miR-146a) is highly expressed in many cell types under homeostatic conditions, and plays an important anti-inflammatory role in myeloid cells. However, its role in podocytes is unclear.

In Diabetic Kidney Disease Urinary Exosomes Better Represent Kidney Specific Protein Alterations Than Whole Urine.

Background: Predicting or diagnosing underlying kidney disease by analyzing whole urine remains the mainstay of nephrology practice. However, whole urine is a poor compartment to assess many structural changes in the kidney because whole urine contains only a few proteins derived from the kidney itself. Urinary exosomes, on the other hand, which are derived from the kidney, contain proteins secreted by the kidney.

Mastitis, a Radiographic, Clinical, and Histopathologic Review.

Mastitis is a benign inflammatory process of the breast with heterogeneous histopathological findings, which clinically and radiographically may mimic a mammary carcinoma. We undertook a retrospective study on 37 cases of mastitis in our institution to correlate the radiographic imaging features and the clinical presentation with the histopathological findings. Histologically, there were 21 granulomatous, 7 fibrous, 3 plasma cell, 3 lupus, 2 lymphocytic, and 1 case of acute mastitis.

Concurrent angiomyolipomas and renal cell neoplasms in patients without tuberous sclerosis: a retrospective study.

Synchronous renal cell neoplasms (RCNs) and angiomyolipomas (AML) occurring in the same kidney are rare. The aim of this retrospective study is to investigate the incidence and clinicopathological features of concurrent AML and RCN in patients without tuberous sclerosis complex (TSC). Partial and radical nephrectomy specimens with a diagnosis of RCN and AML from 1995 to May 2013 were reviewed.

A Small Molecule β2 Integrin Agonist Improves Chronic Kidney Allograft Survival by Reducing Leukocyte Recruitment and Accompanying Vasculopathy.

Kidney allograft rejection is associated with infiltration of inflammatory CD11b+ leukocytes. A CD11b agonist leukadherin-1 (LA1) increases leukocyte adhesion, preventing their transmigration and tissue recruitment in vivo. Here, we test the extent to which LA1-mediated activation of CD11b/CD18 enhances kidney allograft survival in a mouse model of fully MHC-mismatched orthotopic kidney transplantation, where C57BL/6J (H-2(b)) recipients received kidney allografts from Balb/c mice (H-2(d)).

The variable course of women with X-linked Alport Syndrome.

X-linked Alport syndrome (XLAS) arises from mutations in the gene encoding the α5-chain of type IV collagen and is associated with hematuria, ocular abnormalities and high-tone sensorineural hearing loss. Nearly all affected males have decreased kidney function resulting in end-stage renal disease (ESRD) as early as the second decade of life. It was long thought that affected females had a benign outcome; however, in recent decades, it has become quite clear that they too are at risk for developing nephrotic syndrome, decreased kidney function and ESRD.

Resurgence of membranous nephropathy in African Americans in inner city Chicago.

Background: It is well established that the incidence of focal segmental glomerular sclerosis (FSGS) increased from 1970-1990 to become the leading primary glomerular disease in patients of African descent.

Methods: To determine whether this trend has continued in the past years in Chicago, adult, native kidney biopsies from January 2001 to December 2011 at our hospital were reviewed and collected relevant clinical information in patients with a primary glomerular disease including FSGS, membranous nephropathy (MN), minimal change disease (MCD), membranoproliferative glomerulonephritis (MPGN), and IgA nephropathy (IgAN).

Results: In the 204 patients analyzed, MN was the most prevalent (32.

Fine-needle aspiration of metanephric adenoma of the kidney with clinical, radiographic and histopathologic correlation: a review.

Metanephric adenoma of the kidney is an uncommon benign epithelial neoplasm with only a small number of reports that describe its cytologic features. We describe two additional cases of metanephric adenoma diagnosed on fine-needle aspiration biopsy and review the available literature. Our cases showed similar cytology and were composed of cellular smears with numerous clusters of small, oval to round cells arranged in a microfollicular pattern and papillary configurations.

Acute Epstein-Barr virus infection-associated collapsing glomerulopathy.

A 21-year-old woman presenting with acute Epstein-Barr virus (EBV) infection (infectious mononucleosis) was noted to have renal involvement. She had proteinuria, leukocyturia and microscopic hematuria, and 10 days after admission became nephrotic (23 g of protein per g of creatinine). Renal biopsy revealed glomerular tuft collapse, visceral epithelial cell proliferation and vacuolization consistent with collapsing glomerulopathy.

The Oxford classification of IgA nephropathy: a retrospective analysis.

Background/aims: The Oxford classification of IgA nephropathy (IgAN) assesses the presence of mesangial hypercellularity ≥50% (M1 vs. 0), endocapillary proliferation (E1 vs. 0), segmental glomerulosclerosis (S1 vs.

Ancillary studies in determining human papillomavirus status of squamous cell carcinoma of the oropharynx: a review.

Squamous cell carcinoma (SCC) of the oral cavity and pharynx represents the sixth most common form of malignancy worldwide. A significant proportion of these cases are related to human papillomavirus (HPV) infection. In general, HPV-associated SCC is more commonly nonkeratinizing and poorly differentiated, whereas non-HPV-associated SCC is typically keratinizing and moderately differentiated.

Solid variant of papillary renal cell carcinoma with spindle cell and tubular components.

The solid variant of papillary renal cell carcinoma, when strictly defined as a tumor in which no true papillae can be identified, is extremely rare, with only a few cases reported in the literature. This tumor is characterized histologically by solid sheets of cells without true papillae; nevertheless, immunohistochemical and genetic analysis supports the classification of this tumor as a variant of papillary renal cell carcinoma. We report a case of solid variant of papillary renal cell carcinoma affecting a young man and provide histologic and clinical follow-up data, adding an additional case of this extremely rare pathology to the literature.

Fine-needle aspiration diagnosis of a metastatic adult sclerosing rhabdomyosarcoma in a lymph node.

Adult sclerosing rhabdomyosarcoma (ASRMS) is a rare variant of rhabdomyosarcoma with a characteristic histological appearance of small, round cells in a dense, hyalinized stroma. Although nodal metastases of soft-tissue sarcomas are considered uncommon, up to 5% overall are associated with lymph node metastases. Nonetheless, there is little literature on the cytologic characteristics of metastatic soft-tissue sarcomas in lymph nodes, and to our knowledge, there are no reports of nodal metastasis of ASRMS diagnosed by fine-needle aspiration (FNA) cytology.