Scholars@Duke
Mary Helen Foster

Mary Helen Foster

Professor of Medicine
Medicine, Nephrology
foste027@duke.edu
Duke Box 103015, Durham, NC 27710
Msrbii Second Floor, Rm 2018, 106 Research Drive, Durham, NC 27710

Selected Publications

Autoreactive B cells recruited to lungs by silica exposure contribute to local autoantibody production in autoimmune-prone BXSB and B cell receptor transgenic mice.

Journal Article Front Immunol · 2022 Occupational exposure to inhaled crystalline silica dust (cSiO2) is linked to systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and anti-neutrophil cytoplasmic autoantibody vasculitis. Each disease has a characteristic autoantibody pr ... Full text Link to item Cite

Emerging immunotherapies for autoimmune kidney disease.

Journal Article Hum Vaccin Immunother · 2019 Autoimmunity is a leading cause of chronic kidney disease and loss of native and transplanted kidneys. Conventional immunosuppressive therapies can be effective but are non-specific, noncurative, and risk serious side effects such as life-threatening infec ... Full text Link to item Cite

Silica Exposure Differentially Modulates Autoimmunity in Lupus Strains and Autoantibody Transgenic Mice.

Journal Article Front Immunol · 2019 Inhalational exposure to crystalline silica is linked to several debilitating systemic autoimmune diseases characterized by a prominent humoral immune component, but the mechanisms by which silica induces autoantibodies is poorly understood. To better unde ... Full text Link to item Cite

Altered toll-like receptor responsiveness underlies a dominant heritable defect in B cell tolerance in autoimmune New Zealand Black mice.

Journal Article Eur J Immunol · March 2018 Systemic lupus erythematosus is a debilitating autoimmune disease in which autoantibodies and autoreactive T cells destroy kidneys and other organs. Disease is clinically and genetically heterogeneous, suggesting that underlying mechanisms vary between pat ... Full text Link to item Cite

A murine Ig light chain transgene reveals IGKV3 gene contributions to anti-collagen types IV and II specificities.

Journal Article Mol Immunol · November 2017 A subset of autoimmune diseases result from autoantibodies targeting epitopes on matrix collagen. The most extensively studied are anti-glomerular basement membrane glomerulonephritis (or its systemic counterpart Goodpasture's disease) that destroys kidney ... Full text Link to item Cite

Basement membranes and autoimmune diseases.

Journal Article Matrix Biol · January 2017 Basement membrane components are targets of autoimmune attack in diverse diseases that destroy kidneys, lungs, skin, mucous membranes, joints, and other organs in man. Epitopes on collagen and laminin, in particular, are targeted by autoantibodies and T ce ... Full text Link to item Cite

Optimizing the translational value of animal models of glomerulonephritis: insights from recent murine prototypes.

Journal Article Am J Physiol Renal Physiol · September 1, 2016 Animal models are indispensable for the study of glomerulonephritis, a group of diseases that destroy kidneys but for which specific therapies do not yet exist. Novel interventions are urgently needed, but their rational design requires suitable in vivo pl ... Full text Link to item Cite

Uncommon structural motifs dominate the antigen binding site in human autoantibodies reactive with basement membrane collagen.

Journal Article Mol Immunol · August 2016 Autoantibodies mediate organ destruction in multiple autoimmune diseases, yet their origins in patients remain poorly understood. To probe the genetic origins and structure of disease-associated autoantibodies, we engrafted immunodeficient mice with human ... Full text Link to item Cite

Recovery of a human natural antibody against the noncollagenous-1 domain of type IV collagen using humanized models.

Journal Article J Transl Med · June 6, 2015 BACKGROUND: Anti-glomerular basement membrane nephritis and Goodpasture syndrome result from autoantibody (Ab)-mediated destruction of kidney and lung. Ab target the noncollagenous 1 (NC1) domain of alpha3(IV) collagen, but little is known about Ab origins ... Full text Link to item Cite

Lack of galectin-1 or galectin-3 alters B cell deletion and anergy in an autoantibody transgene model.

Journal Article Glycobiology · July 2013 Members of the galectin family of proteins have been shown to regulate the development and the function of immune cells. We previously identified the increased expression of galectin-1 and galectin-3 mRNA and protein in anergic B cells relative to their na ... Full text Link to item Cite

Regulation of basement membrane-reactive B cells in BXSB, (NZBxNZW)F1, NZB, and MRL/lpr lupus mice.

Journal Article Autoimmunity · May 2013 Autoantibodies to diverse antigens escape regulation in systemic lupus erythematosus under the influence of a multitude of predisposing genes. To gain insight into the differential impact of diverse genetic backgrounds on tolerance mechanisms controlling a ... Full text Link to item Cite

Genetic elimination of α3(IV) collagen fails to rescue anti-collagen B cells.

Journal Article Immunol Lett · December 30, 2011 Organ deposition of autoantibodies against the noncollagenous-1 domain of the α3 chain of type IV collagen leads to severe kidney and lung injury in anti-glomerular basement membrane disease. The origin and regulation of these highly pathogenic autoantibod ... Full text Link to item Cite

Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis.

Journal Article J Clin Invest · April 2009 Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin (AT1) receptors in glomerular inflammation associated with autoimmune disease, we genera ... Full text Link to item Cite

Systemic lupus erythematosus and the kidney

Journal Article · December 1, 2008 Full text Cite

Central tolerance regulates B cells reactive with Goodpasture antigen alpha3(IV)NC1 collagen.

Journal Article J Immunol · November 1, 2008 Featured Publication Patients and rodents with Goodpasture's syndrome (GPS) develop severe autoimmune crescentic glomerulonephritis, kidney failure, and lung hemorrhage due to binding of pathogenic autoantibodies to the NC1 domain of the alpha3 chain of type IV collagen. Targe ... Full text Link to item Cite

Novel targets for immunotherapy in glomerulonephritis.

Journal Article Biologics · September 2008 Featured Publication Glomerulonephritis is a common cause of chronic kidney disease and end stage renal failure. Current therapy relies on variably effective, nonspecific and toxic immunosuppression. Recent insights into underlying biology and disease pathogenesis in human glo ... Full text Link to item Cite

Tracking Differential Gene Expression in MRL/MpJ Versus C57BL/6 Anergic B Cells: Molecular Markers of Autoimmunity.

Journal Article Biomark Insights · June 10, 2008 Featured Publication BACKGROUND: Anergy is a key mechanism controlling expression of autoreactive B cells and a major site for failed regulation in autoimmune diseases. Yet the molecular basis for this differentiated cell state remains poorly understood. The current lack of we ... Full text Link to item Cite

Multifunctional regulators of cell growth are differentially expressed in anergic murine B cells.

Journal Article Mol Immunol · February 2007 Featured Publication Defective anergy is a major cause of failed tolerance and is amenable to therapeutic manipulation. To better define the molecular basis of anergy in B cells tolerized by matrix self-antigen, we used complementary approaches of representational difference a ... Full text Link to item Cite

T cells and B cells in lupus nephritis.

Journal Article Semin Nephrol · January 2007 Featured Publication T and B lymphocytes play diverse roles at multiple stages in the development and progression of lupus nephritis. Disruption of T- and B-cell regulatory functions by environmental and genetic influences permits pathogenic effectors to emerge in disease. New ... Full text Link to item Cite

Deconstructing B cell tolerance to basement membranes.

Journal Article Arch Immunol Ther Exp (Warsz) · 2006 Featured Publication Basement membrane antigens are frequent targets of autoantibody attack in systemic and organ-restricted autoimmunity. These specialized and highly organized matrices are composed of multiple components with restricted tissue distributions and limited epito ... Full text Link to item Cite

Treatment with a laminin-derived peptide suppresses lupus nephritis.

Journal Article J Immunol · October 15, 2005 The role of DNA as the target for pathogenic lupus autoantibodies in systemic lupus erythematosus is equivocal and renal damage may be due to cross-reactivity of lupus Abs with glomerular components. We have previously shown that lupus autoantibodies bind ... Full text Link to item Cite

Kappa editing rescues autoreactive B cells destined for deletion in mice transgenic for a dual specific anti-laminin Ig.

Journal Article J Immunol · May 1, 2004 Featured Publication We explored mechanisms involved in B cell self-tolerance in a double- and triple-transgenic mouse model bearing the LamH-C mu Ig H chain conventional transgene and a gene-targeted replacement for a functional V kappa 8J kappa 5 L chain gene. Whereas the H ... Full text Link to item Cite

Tracking immune tolerance in autoimmune susceptible mice.

Conference JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY · November 1, 2003 Link to item Cite

Dissecting the biochemical basis of tolerance: Role for differential activation of MAPKs, NF-kB and NFAT.

Journal Article JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY · September 1, 2002 Link to item Cite

Defining immune tolerance through gene expression profiling.

Journal Article JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY · September 1, 2002 Link to item Cite

Complex tolerance phenotypes induced by lupus autoantigens.

Journal Article JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY · September 1, 2002 Link to item Cite

Humoral autoimmunity to basement membrane antigens is regulated in C57BL/6 and MRL/MpJ mice transgenic for anti-laminin Ig receptors.

Journal Article J Immunol · June 1, 2002 Featured Publication Basement membrane proteins are targeted in organ-limited and systemic autoimmune nephritis, yet little is known about the origin or regulation of immunity to these complex extracellular matrices. We used mice transgenic for a nephrotropic systemic lupus er ... Full text Link to item Cite

In vitro and in vivo expression of a nephritogenic Ig heavy chain determinant: pathogenic autoreactivity requires permissive light chains.

Journal Article Immunol Cell Biol · June 2001 Lymphocyte antigen receptors are promising targets for immune intervention strategies in disorders marked by repertoire skewing or expansion of lymphocyte subsets. Appropriate application of immune receptor modulation is predicated on understanding the rol ... Full text Link to item Cite

Chronic salicylism resulting in noncardiogenic pulmonary edema requiring hemodialysis.

Journal Article Am J Kidney Dis · September 2000 Salicylate intoxication is frequently overlooked as a cause of noncardiogenic pulmonary edema and altered mental status in adult patients. We describe a 42-year-old woman who presented with two episodes of recurrent noncardiogenic pulmonary edema requiring ... Full text Link to item Cite

Diverse endogenous light chains contribute to basement membrane reactivity in nonautoimmune mice transgenic for an anti-laminin Ig heavy chain.

Journal Article Immunogenetics · January 2000 Basement membrane proteins are targeted in a variety of pathologic autoimmune responses, yet little is known regarding the origins and regulation of this subset of pathogenic lymphocytes. To examine the generation and fate of B cells reactive with a matrix ... Full text Link to item Cite

Antiidiotypic antibody recognizes an amiloride binding domain within the alpha subunit of the epithelial Na+ channel.

Journal Article J Biol Chem · April 2, 1999 We previously raised an antibody (RA6.3) by an antiidiotypic approach which was designed to be directed against an amiloride binding domain on the epithelial Na+ channel (ENaC). This antibody mimicked amiloride in that it inhibited transepithelial Na+ tran ... Full text Link to item Cite

Lupus nephritis: update on pathogenesis and disease mechanisms.

Journal Article Semin Nephrol · March 1999 Immune-mediated nephritis is a common complication of systemic lupus erythematosus (SLE). It is now clear that multiple and independent mechanisms contribute to disease onset and pathogenesis, which may explain the remarkable phenotypic and histopathologic ... Link to item Cite

Membranoproliferative glomerulonephritis type I, mixed cryoglobulinemia and lymphoma in the absence of hepatitis C infection.

Journal Article Am J Nephrol · 1999 Chronic hepatitis C virus infection has been linked to cryoglobulinemia, membranoproliferative glomerulonephritis, and malignant B-cell lymphoproliferation, suggesting a possible pathogenetic link between these disorders. We report a patient with the latte ... Full text Link to item Cite

Relevance of systemic lupus erythematosus nephritis animal models to human disease.

Journal Article Semin Nephrol · January 1999 Systemic lupus erythematosus (SLE) is characterized by spontaneous B and T cell autoreactivity and multiorgan immune injury including severe glomerulonephritis. This autoimmune syndrome results from a global derangement in immune regulation dependent on th ... Link to item Cite

Anti-idiotypic monoclonal Ig specific for an anti-laminin Ig heavy chain transgene variable region.

Journal Article Hybridoma · August 1998 Techniques currently available to obtain anti-idiotypic reagents reactive with a single chain of a lymphocyte antigen receptor rely on immunization with intact soluble or cell-bound Ig or T-cell receptors. Ready recovery of single-chain-specific monoclonal ... Full text Link to item Cite

Lupus-like nephrotropic autoantibodies in non-autoimmune mice harboring an anti-basement membrane/anti-DNA Ig heavy chain transgene.

Journal Article Mol Immunol · February 1998 Autoantibodies target a diverse group of tissue antigens in human and experimental autoimmune nephritis. The proximal events that generate and regulate these various pathogenic Ab remain obscure. To examine the origins and fate in normal mice of autoantibo ... Full text Link to item Cite

The nephritogenic immune response.

Journal Article Curr Opin Nephrol Hypertens · May 1997 Featured Publication Recent insights into the etiopathogenesis of nephritogenic immune responses are derived primarily from experimental models of systemic and organ-specific autoimmunity. Genetic analyses and immune-related gene ablation studies indicate that multiple indepen ... Full text Link to item Cite

Anti-laminin reactivity and glomerular immune deposition by in vitro recombinant antibodies.

Journal Article Autoimmunity · 1997 Growing evidence suggests that recombinatorial events prior to antigen contact can generate pathogenic autoantibodies in the nonautoimmune individual, thus providing potential disease mediators if conditions arise that permit bypass of tolerance and activa ... Full text Link to item Cite

Structural features of nephritogenic lupus autoantibodies.

Journal Article Methods · January 1997 We have identified monoclonal antibodies derived from MRL-lpr/lpr lupus-prone mice that produced nephritis after passive transfer to normal mice. Our present goal was to elucidate the structural and immunochemical features of nephritogenic Ig that facilita ... Full text Link to item Cite

Lupus autoantibodies interact directly with distinct glomerular and vascular cell surface antigens.

Journal Article Kidney Int · May 1996 We have identified monoclonal anti-DNA antibodies derived from lupus prone MRL-lpr/lpr mice that produce glomerular immune deposits and nephritis after passive transfer to normal mice. Particularly noteworthy is that the location of immune deposition varie ... Full text Link to item Cite

A subgroup of murine monoclonal anti-deoxyribonucleic acid antibodies traverse the cytoplasm and enter the nucleus in a time-and temperature- dependent manner.

Journal Article Lab Invest · July 1994 BACKGROUND: The capacity of lupus autoantibodies to enter living cells and bind to molecules for which they have intrinsic affinity is not well appreciated. In previous studies, we identified a subgroup of three murine monoclonal IgG anti-DNA antibodies, d ... Link to item Cite

Topology of an amiloride-binding protein.

Journal Article J Biol Chem · January 28, 1994 Amiloride and structurally related compounds inhibit many transport proteins, enzymes, and drug or hormone receptors, although the topology of amiloride binding sites on these proteins has not been defined. We have previously raised and characterized a mon ... Link to item Cite

Molecular and structural analysis of nuclear localizing anti-DNA lupus antibodies.

Journal Article Immunol Res · 1994 Featured Publication To determine the structure of three nuclear localizing lupus anti-DNA immunoglobulins (Igs) and to search for clues to mechanisms of cellular and/or nuclear access, their H- and L-chain variable region sequences were determined and subjected to three-dimen ... Full text Link to item Cite

Structural properties of a subset of nephritogenic anti-DNA antibodies.

Journal Article Immunol Res · 1994 Structural analysis of lupus autoantibodies is beginning to provide clues to the molecular basis for antigenic specificity and pathogenicity. The present analysis indicates that multiple light and heavy chains contain residues which can facilitate DNA bind ... Full text Link to item Cite

Molecular analysis of spontaneous nephrotropic anti-laminin antibodies in an autoimmune MRL-lpr/lpr mouse.

Journal Article J Immunol · July 15, 1993 Featured Publication To explore the genetic relationship between anti-laminin and anti-DNA autoantibodies (autoAb), VH gene and gene family expression were determined among autoAb derived from an individual 6-mo-old MRL-lpr/lpr mouse. Whereas 85% of the anti-DNA Ig were identi ... Link to item Cite

Independently derived murine glomerular immune deposit-forming anti-DNA antibodies are encoded by near-identical VH gene sequences.

Journal Article J Clin Invest · February 1993 To examine the influence of variable region sequences on the capacity of individual lupus autoantibodies (autoAb) to form glomerular immune deposits, the complete VH and VL region sequences of three anti-DNA mAb that produced morphologically similar immune ... Full text Link to item Cite

Anti-DNA antibodies form immune deposits at distinct glomerular and vascular sites.

Journal Article Kidney Int · June 1992 To investigate the capacity of lupus autoAb to produce glomerular immune deposits (ID) and nephritis, 24 murine monoclonal (m) anti-DNA antibodies (Ab), derived from either MRL-lpr/lpr, SNF1 or NZB lupus-prone mice and selected based on properties shared w ... Full text Link to item Cite

Variable region sequence analysis of anti-DNA antibodies: evidence for a family of closely related germ-line VH genes encoding lupus autoantibodies.

Journal Article DNA Cell Biol · April 1992 Cloning and sequencing of the V regions of the anti-DNA monoclonal antibodies (mAbs), H438 and H130, indicate that H438 is encoded by a J558 VH gene, a single D region nucleotide, and unmutated JH1, V kappa-1C and J kappa 1 genes, and the H130 L chain is e ... Full text Link to item Cite

Murine monoclonal anti-DNA antibodies penetrate cells, bind to nuclei, and induce glomerular proliferation and proteinuria in vivo.

Journal Article J Am Soc Nephrol · February 1992 The production of relatively high quantities of autoantibodies (autoAb) that react with DNA and other intranuclear antigens is characteristic of individuals with systemic lupus erythematosus and other autoimmune diseases. However, the capacity of these Ab ... Full text Link to item Cite

VH gene analysis of spontaneously activated B cells in adult MRL-lpr/lpr mice. J558 bias is not limited to classic lupus autoantibodies.

Journal Article J Immunol · September 1, 1991 Featured Publication To determine the genetic origins of lupus auto-antibodies, we analyzed the relationship between VH gene usage and auto-Ag-binding properties of 352 B cell hybridomas derived from MRL-lpr/lpr mice. The hybridomas were derived from neonatal, 1-month-old, 3-m ... Link to item Cite

Prolonged survival with a remnant kidney.

Journal Article Am J Kidney Dis · March 1991 Surgical ablation of five-sixths renal mass in Munich-Wistar rats fed a high protein diet leads to focal sclerosis in the remnant kidney and progressive renal failure. Experimental data suggest that this injury results from intraglomerular hypertension and ... Full text Link to item Cite