TLR tolerance reduces IFN-alpha production despite plasmacytoid dendritic cell expansion and anti-nuclear antibodies in NZB bicongenic mice.

Genetic loci on New Zealand Black (NZB) chromosomes 1 and 13 play a significant role in the development of lupus-like autoimmune disease. We have previously shown that C57BL/6 (B6) congenic mice with homozygous NZB chromosome 1 (B6.NZBc1) or 13 (B6.

Epistatic suppression of fatal autoimmunity in New Zealand black bicongenic mice.

Numerous mapping studies have implicated genetic intervals from lupus-prone New Zealand Black (NZB) chromosomes 1 and 4 as contributing to lupus pathogenesis. By introgressing NZB chromosomal intervals onto a non-lupus-prone B6 background, we determined that: NZB chromosome 1 congenic mice (denoted B6.NZBc1) developed fatal autoimmune-mediated kidney disease, and NZB chromosome 4 congenic mice (denoted B6.

Abrogation of pathogenic IgG autoantibody production in CD40L gene-deleted lupus-prone New Zealand Black mice.

New Zealand Black (NZB) mice spontaneously develop a lupus-like autoimmune disease. Since CD40-CD40L interactions are important for B cell class-switch recombination and germinal center formation, we sought to understand the impact of these interactions on the immune abnormalities in NZB CD40L gene-deleted (CD40L(-/-)) mice in vivo. NZB.

Dissociation of the genetic loci leading to b1a and NKT cell expansions from autoantibody production and renal disease in B6 mice with an introgressed New Zealand Black chromosome 4 interval.

Previous mapping studies have linked New Zealand Black (NZB) chromosome 4 to several lupus traits, including autoantibody production, splenomegaly, and glomerulonephritis. To confirm the presence of these traits, our laboratory introgressed homozygous NZB chromosome 4 intervals extending from either 114 to 149 Mb or 32 to 149 Mb onto the lupus-resistant C57BL/6 background (denoted B6.NZBc4S and B6.

Immunization with an apoptotic cell-binding protein recapitulates the nephritis and sequential autoantibody emergence of systemic lupus erythematosus.

The initial events predisposing to loss of tolerance in patients with systemic lupus erythematosus (SLE) are largely unknown, as are the events that precipitate the transition from preclinical to overt disease. We hypothesized that induction of murine SLE would require tipping the balance between tolerance and immunity in two ways: 1) an immunogen that could take advantage of apoptotic cells as a scaffold for epitope spread, and 2) an immune activator that would generate a strong and persistent T cell response to the inciting immunogen. We show that immunization of C57BL/6 and BALB/c mice with human beta(2)-glycoprotein I, an apoptotic cell-binding protein, in the presence of LPS induces a long-lived, potent response to beta(2)-glycoprotein I that results in epitope spread to multiple SLE autoantigens.

Colocalization of expansion of the splenic marginal zone population with abnormal B cell activation and autoantibody production in B6 mice with an introgressed New Zealand Black chromosome 13 interval.

Polyclonal B cell activation is a prominent feature of the lupus-prone New Zealand Black (NZB) mouse strain. We have previously demonstrated linkage between a region on NZB chromosome 13 and increased costimulatory molecule expression on B cells. In this study we have produced C57BL/6 congenic mice with an introgressed homozygous NZB interval extending from approximately 24 to 73 cM on chromosome 13 (denoted B6.

Necrotizing glomerulonephritis caused by Bartonella henselae endocarditis.

Glomerulonephritis secondary to endocarditis is uncommon and usually associated with valvular infection by blood culture-positive bacteria. We report 3 cases of necrotizing glomerulonephritis associated with culture-negative endocarditis caused by Bartonella henselae. Two of the patients presented with renal abnormalities and were investigated for endocarditis after results of renal biopsy.

Functional dissection of lupus susceptibility loci on the New Zealand black mouse chromosome 1: evidence for independent genetic loci affecting T and B cell activation.

In previous work, we demonstrated linkage between a broad region on New Zealand Black (NZB) chromosome 1 and increased costimulatory molecule expression on B cells and autoantibody production. In this study, we produced C57BL/6 congenic mice with homozygous NZB chromosome 1 intervals of differing lengths. We show that both B6.

Polyomavirus infection and acute vascular rejection in a kidney allograft: coincidence or mimicry?

During the past decade, polyoma virus (PV) infection has emerged as an important cause of graft dysfunction and failure in kidney transplant recipients. Establishing the correct diagnosis can be difficult, however, because the histologic appearance of PV infection can resemble acute cellular rejection. We report a kidney-pancreas transplant recipient with PV infection, in whom both vascular and cellular rejection were dominant histologic features in a renal biopsy specimen.

Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases.

Kidney disease affects over 20 million people in the United States alone. Although the causes of renal failure are diverse, the glomerular filtration barrier is often the target of injury. Dysregulation of VEGF expression within the glomerulus has been demonstrated in a wide range of primary and acquired renal diseases, although the significance of these changes is unknown.

Improvement in human decay accelerating factor transgenic porcine kidney xenograft rejection with intravenous administration of gas914, a polymeric form of alphaGAL.

Background: The present study was undertaken to determine whether intravenous administration of GAS914, a polymeric form of alphaGal, would minimize porcine kidney xenograft rejection in baboons. Human decay accelerating factor renal xenografts were transplanted into 16 baboon recipients.

Methods: Baseline immunosuppression for all groups included cyclosporine A, cyclophosphamide, SDZ-RAD, and methylprednisolone.

Primary large cell neuroendocrine carcinoma of the urinary bladder.

Reports of primary large cell neuroendocrine carcinomas of the urinary bladder are few; we identified only 2 cases in the literature. Both of these cases involved male patients with rapid progression of disease culminating in death with widespread metastases. We report a case of primary large cell neuroendocrine carcinoma of the bladder, with an admixed minor element of adenocarcinoma, in an 82-year-old man.

Improvement in rejection of human decay accelerating factor transgenic pig-to-primate renal xenografts with administration of rabbit antithymocyte serum.

Background: Survival in pig-to-baboon kidney xenotransplantation is currently limited by acute humoral xenograft rejection (AHXR). We hypothesized that the administration of rabbit antithymocyte serum (RATS) would delay or prevent AHXR as compared with a cyclophosphamide (CyP)-based immunosuppressive regimen.

Methods: Nine baboons received life-supporting heterotopic single-kidney transplants from human decay accelerating factor transgenic pigs.