Tiffany Nicole Caza

Arkana Laboratories

Introduction Primary membranous nephropathy (PMN) is uncommon in children. Therefore, data on the clinical course of affected children are scarce. In recent years, several novel antigens have been implicated in the pathogenesis of PMN. However, the histopathologic characteristics of pediatric patients with PMN remain poorly represented in the liter...

Antitubular basement membrane (anti-TBM) antibody disease is an extremely rare disorder. It may be idiopathic or secondary to exposure of the proximal tubular basement membrane, triggered by tubular injury due to acute pyelonephritis, acute allergic interstitial nephritis, or kidney allograft rejection. The histopathology of anti-TBM antibody disea...

Drugs are an important secondary cause of membranous nephropathy (MN) with the most common drugs associated with MN being nonsteroidal anti-inflammatory drugs (NSAIDs). Since the target antigen in NSAID-associated MN is not known, we performed laser microdissection of glomeruli followed by mass spectrometry (MS/MS) in 250 cases of PLA2R-negative MN...

Purpose of review: Multiple antigenic targets were discovered in membranous nephropathy, representing distinct autoimmune diseases with a similar morphologic pattern of injury. An overview of recent developments, including antigen types, clinical associations, serologic monitoring, and advancements in understanding disease pathogenesis are provide...

Glomerular disease is an important complication in patients undergoing hematopoietic stem cell transplantation (HSCT), impacting approximately 1–2% of all HSCT recipients and equating to 700–1400 cases per year worldwide. Development of kidney disease in HSCT recipients is often multifactorial and a kidney biopsy is required to identify the underly...

Multiple autoantigens have been identified in membranous nephropathy (MN) by tissue-based proteomics. However, antigenic targets of disease are unknown for over 10% of patients with MN and over half of those with membranous lupus nephritis (MLN). Here, we identified multiple new targets in PLA2R-/THSD7A-/EXT-/NELL1-quadruple negative MN biopsies th...

Key Points IgAN and MCD are the most common de novo glomerular diseases reported after COVID-19 vaccination, particularly after mRNA vaccination. Membranous nephropathy, pauci-immune GN, and collapsing GN have also been attributed to COVID-19 vaccination, some with dual histologies. Recovery of kidney function and proteinuria remission is more like...

Introduction Renal intravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive B-cell lymphoma with neoplastic cells occupying the vascular lumina with only 53 patients reported to date. Here, we present the largest case series to characterize this rare disease. Methods We performed a multi-institutional, retrospective review of kidney biop...

Kidney pathology education is a critical component in training of nephrology fellows, as well as for continuing medical education for practicing nephrologists. Kidney pathology images are included on nephrology fellow board exams, and clinicopathologic correlation of kidney biopsy findings is critical in everyday clinical practice. Nephropathology...

Membranous nephropathy (MN) is an immune kidney disease characterized by glomerular subepithelial immune complexes (ICs) containing antigen, IgG, and products of complement activation. Whereas proteinuria is caused by complement-mediated podocyte injury, the pathways of complement activation remain controversial due to the predominance of IgG4 in I...

Background EXT1/2 and NCAM1 associated membranous lupus nephritis (MLN) may represent distinct disease phenotypes with prognostic significance. Methods We searched our archives for patients with systemic lupus erythematous (SLE) and at least two kidney biopsies demonstrating MLN. Each biopsy was stained for EXT1 and NCAM1 and scored as positive or...

Pro-inflammatory immune system development, metabolomic defects, and deregulation of autophagy play interconnected roles in driving the pathogenesis of systemic lupus erythematosus (SLE). Lupus nephritis (LN) is a leading cause of morbidity and mortality in SLE. While the causes of SLE have not been clearly delineated, skewing of T and B cell diffe...

Despite the current standard of care, breast cancer remains one of the leading causes of mortality in women worldwide, thus emphasizing the need for better predictive and therapeutic targets. ABI1 is associated with poor survival and an aggressive breast cancer phenotype, although its role in tumorigenesis, metastasis and the disease outcome remain...

Anti-brush border antibody (ABBA) disease is a rare form of tubulointerstitial nephritis associated with autoantibodies to LDL related protein 2 (LRP2, also known as megalin). It typically affects elderly men and is associated with progressive loss of kidney function. Characteristic findings on biopsy are acute tubular injury with variable levels o...

The identification of the major target antigen phospholipase A2 receptor (PLA2R) in the majority of primary (idiopathic) cases of membranous nephropathy (MN) has been followed by the rapid identification of numerous minor antigens that appear to define phenotypically distinct forms of disease. This article serves to review all the known antigens th...

Introduction: Fibrillary glomerulonephritis (FGN) is a rare glomerular disease with poor prognosis, characterized by deposition of randomly arranged fibrillar material measuring 10-30 nm in diameter. This diagnosis is confirmed with DNAJB9 immunohistochemistry as well as ultrastructural examination. Ultrastructurally, the fibrillary material seen...

Background Immune responses to vaccination are a known trigger for a new onset of glomerular disease or disease flare in susceptible individuals. Mass immunization against SARS-CoV-2 in the COVID-19 pandemic provides a unique opportunity to study vaccination-associated autoimmune kidney diseases. In the recent literature, there are several patient...

Introduction: Anti-LDL receptor-related protein 2 (anti-LRP2) nephropathy is a rare but progressive form of autoimmune-mediated tubulointerstitial nephritis and glomerular disease, characterized by a classic pattern of immune complex deposition in the kidney. A theoretic link between autoimmune disease and lymphoproliferative diseases exists, and...

Objectives: To determine the prevalence of patients who require vaginal cavity remnant excision and obliteration during neourethral stricture repair and to characterize the histological composition of the excised tissue. Methods: A retrospective review was performed of all transgender men who underwent neourethral stricture repair. Preoperative...

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19) resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 all...

Background Membranous lupus nephritis (MLN) comprises 10%–15% of lupus nephritis and increases morbidity and mortality of patients with SLE through complications of nephrotic syndrome and chronic kidney failure. Identification of the target antigens in MLN may enable noninvasive monitoring of disease activity, inform treatment decisions, and aid in...

Membranous lupus nephritis is a frequent cause of nephrotic syndrome in patients with systemic lupus erythematosus. It has been shown in phospholipase A2 receptor positive membranous; nephropathy that known antibodies can be detected within sera, determination of the target; autoantigen can have diagnostic significance, inform prognosis, and enable...

Purpose To validate a novel method of urethral stricture treatment using liquid buccal mucosal grafts (LBMG) to augment direct vision internal urethrotomy (DVIU) in an animal model. Materials and methods A rabbit stricture model was used to test this method. Strictures were induced in 26 rabbits using electroresection of urethral epithelium. The a...

Purpose: To evaluate histological changes in stenotic urethral tissue post-radiation therapy. Treatment of prostate cancer by radiation therapy carries a risk of off-target injury to the membranous urethra causing urethral stenosis. Limited characterization of post-radiation urethral stenosis exists in the literature. We hypothesize that specific...

Reports of collapsing glomerulopathy in patients of African ancestry and high-risk APOL1 genotype infected with SARS-CoV-2 have emerged during the COVID-19 pandemic. This new entity, which we term COVID-19-associated nephropathy (COVAN), may particularly impact individuals in some regions of the world. Awareness of this potentially ominous complica...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Patients with membranous nephropathy have an increased risk of malignancy compared to the general population, but the target antigen for malignancy-associated membranous nephropathy is unknown. To explore this, we utilized mass spectrometry for antigen discovery in malignancy-associated membranous nephropathy examining immune complexes eluted from...

Coronavirus Disease-19 (COVID-19), caused by the coronavirus SARS-CoV-2, was initially recognized in Wuhan, China and subsequently spread to all continents. The disease primarily affects the lower respiratory system, but may involve other organs and systems. Histopathologic evaluation of tissue from affected patients is crucial for diagnostic purpo...

Background: Kidney involvement is a feature of COVID-19 and it can be severe in black patients. Previous research linked increased susceptibility to collapsing glomerulopathy, including in patients with HIV-associated nephropathy, to apo L1 (APOL1) variants that are more common in those of African descent. Methods: To investigate genetic, histop...

Anti-LDL Receptor-Related Protein 2 (Anti-LRP2) nephropathy is a rare form of kidney disease that affects the older patients and is characterized with acute kidney injury (AKI) and progressive renal tubular injury associated with IgG immune complex deposits along the basement membrane of proximal tubules, and circulating autoantibodies to the proxi...

Background Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiency syndromes, affecting one in 25,000–50,000 people. Renal insufficiency occurs in approximately 2% of patients with CVID. To date, there are no case series of renal biopsies from patients with CVID, making it difficult to determine whether individual...

Overexpression and long terminal repeat (LTR) polymorphism of the HRES-1/Rab4 human endogenous retrovirus locus have been associated with T-cell activation and disease manifestations in systemic lupus erythematosus (SLE). Although genomic DNA methylation is overall diminished in SLE, its role in HRES-1/Rab4 expression is unknown. Therefore, we dete...

Background: Prostate cancer development involves various mechanisms, which are poorly understood but pointing to epithelial mesenchymal transition (EMT) as the key mechanism in progression to metastatic disease. ABI1, a member of WAVE complex and actin cytoskeleton regulator and adaptor protein, acts as tumor suppressor in prostate cancer but the...

Membranous-like glomerulopathy with masked IgG kappa deposits (MGMID) is a recently described pattern of glomerulonephritis with a unique histopathology. The pattern is characterized by subepithelial and/or mesangial immune deposits that are "masked", to immunoglobulin staining by routine immunofluorescence but strongly stain for IgG and kappa ligh...

Rationale: Thrombotic microangiopathy (TMA) is a group of clinical syndromes characterized by excessive platelet activation and endothelial injury that leads to acute or chronic microvascular obliteration by intimal mucoid and fibrous thickening, with or without associated thrombi. It frequently involves the kidney but may involve any organ or sys...

280 Background: Prostate cancer is characterized by heterogeneity of mechanisms which are poorly understood but pointing to epithelial plasticity as the key mechanism in progression to metastatic disease. ABI1, a member of WAVE complex and actin cytoskeleton regulator and adaptor protein, is proposed to act as tumor suppressor in prostate cancer, b...

Breast cancer is the most commonly diagnosed non-cutaneous cancer in American women and is estimated to cause 40,000 deaths this year. Despite standard of care, breast cancer patients often relapse after a few years of treatment thus highlighting the need for new molecular targets for improved management of metastatic disease. Abelson interactor 1...

This study aims to elucidate the role of Abelson interactor 1 (Abi1), a key protein in the WAVE regulatory complex, in mammary carcinogenesis and metastasis. Breast cancer is the second-leading cause of mortality in women in the United States with an estimated ~200,000 new cases and over 40,000 deaths this year. Despite current treatment modalities...

Beckwith-Wiedemann syndrome (BWS) is a genetic disorder at chromosome 11p15 that leads to increased activity of insulin-like growth factor-2 (IGF2) and reduced activity, with no active copy of the inhibitor of cell proliferation, CDKN1C, resulting in excessive growth and increased risk of tumour formation. Isolated cases of patients with Beckwith-W...

Tubulointerstitial nephritis (TIN) is not commonly associated in aminosalicylate-naïve patients with Crohn’s disease (CD). Our case describes the initial presentation, diagnosis, and management of an adolescent presenting with TIN and underlying CD. Our case emphasizes that CD should be considered in the differential diagnosis of interstitial nephr...

Loeys-Dietz syndrome is a rare autosomal dominant connective tissue disorder with a genetic predisposition to aneurysm formation and congenital cardiofacial defects through genetic mutation affecting the transforming growth factor-beta (TGFβ) signaling pathway. We present a case of a 6-year-old female patient with Loeys-Dietz syndrome who developed...

Figure S1. Representative O2 consumption via complex II of the ETC by mitochondria isolated from livers of 4‐week‐old C57BL/6 (B6), C57BL/6.lpr (lpr), MRL, and MRL/lpr mice. ETC activity was measured in the absence and presence of substrates specific for complex II using Oxygraph, a Clark‐type O2 electrode (Hansatech, Norfolk, UK), as earlier descr...

Background/aim: Only a minority of men succumb to prostate cancer (PCa). Therapy to prevent progression would change treatment paradigms. We investigated the effect of valproic acid (VPA) on PCa cell proliferation and the effects on both angiogenesis and PCa-specific signaling. Materials and methods: LNCaP cells were treated with VPA for 72 h an...

Background: Anti-phospholipid antibodies (aPL) constitute a diagnostic criterion of systemic lupus erythematosus (SLE). aPL have been linked to liver disease in SLE. Since the mechanistic target of rapamycin (mTOR) is a regulator of oxidative stress, which contributes to the development of aPL, we examined the involvement of liver mitochondria in...

Purpose: To describe a novel method of urethral stricture treatment using liquid buccal mucosal grafts (LBMG) to augment direct vision internal urethrotomy (DVIU). Materials and methods: A rabbit stricture model was used to test this method. In Phase-1, the concept of endoscopic LBMG implantation was tested by performing DVIU in three rabbits an...

The molecular chaperone Hsp90 protects deregulated signaling proteins that are vital for tumor growth and survival. Tumors generally display sensitivity and selectivity toward Hsp90 inhibitors; however, the molecular mechanism underlying this phenotype remains undefined. We report that the mitotic checkpoint kinase Mps1 phosphorylates a conserved t...

Purpose: To evaluate the urinary and erectile functional outcomes after dorsal onlay urethroplasty for bulbomembranous urethral strictures. To understand the functional implications of dissection of the posterior urethra. Materials and methods: We report on men who underwent membranous urethral stricture repair by buccal mucosal graft dorsal onl...

The remarkable plasticity of CD4 + T cells allows individuals to respond to environmental stimuli in a context-dependent manner. A balance of CD4 + T cell subsets is critical to mount responses against pathogen challenges to prevent inappropriate activation, to maintain tolerance, and to participate in antitumor immune responses. Specification of s...

Supplemental figure 1: Simplified diagram of CD4+ T cell lineage commitment. Numbers over arrows correspond to types of experiments described in Table 2, which are used to identify the effector molecule following the arrow. Supplemental table 1: Experiments used to study CD4+ T cell subset specification.

The ability of Heat Shock Protein 90 (Hsp90) to hydrolyze ATP is essential for its chaperone function. The co-chaperone Aha1 stimulates Hsp90 ATPase activity, tailoring the chaperone function to specific "client" proteins. The intracellular signaling mechanisms directly regulating Aha1 association with Hsp90 remain unknown. Here, we show that c-Abl...

Takotsubo cardiomyopathy is a newly recognized cause of chest pain mimicking a myocardial infarction in post-menopausal women. It is diagnosed based on clinical criteria established at the Mayo Clinic and imaging studies, including echocardiography, cardiac MRI, angiography, and left ventriculography. Several hypotheses have been postulated towards...

Urothelial carcinoma, or transitional cell carcinoma, is the most common urologic malignancy that carries significant morbidity, mortality, recurrence risk and associated health care costs. Despite use of current chemotherapies and immunotherapies, long-term remission in patients with muscle-invasive or metastatic disease remains low, and disease r...

Background Despite the high prevalence of liver dysfunction in systemic lupus erythematosus (SLE), the role of the liver in disease pathogenesis is still widely unknown. Recently, we showed that prior to disease onset, SLE splenocytes overexpress the small GTPase HRES-1/Rab4A and the mechanistic target of rapamycin (mTOR), which regulate endosomal...

Sarcoidosis is an immune-mediated multisystem disease characterized by the formation of non-caseating granulomas. The pathogenesis of sarcoidosis is unclear, with proposed infectious or environmental antigens triggering an aberrant immune response in susceptible hosts. Multiple pro-inflammatory signaling pathways have been implicated in mediating m...

Infectious agents are considered to be crucial environmental factor in the etiopathogenesis of systemic lupus erythematosus (SLE). Infections may serve as initial trigger to the development of autoimmunity and carry an overall greater risk of morbidity and mortality than the general population. Initial presentation of SLE can mimic infections, and...

Accumulation of mitochondria underlies T-cell dysfunction in systemic lupus erythematosus (SLE). Mitochondrial turnover involves endosomal traffic regulated by HRES-1/Rab4, a small GTPase that is overexpressed in lupus T cells. Therefore, we investigated whether (1) HRES-1/Rab4 impacts mitochondrial homeostasis and (2) Rab geranylgeranyl transferas...

Systemic lupus erythematosus, in both animal models and in humans, is characterized by autoantibody production followed by immune complex deposition in target tissues. Ensuing target organ damage is modulated by reactive intermediates, including reactive nitrogen and oxygen species, through as of now incompletely understood mechanisms. Endothelial...