Faculty Bibliography
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720
Serum Albumin at 12 Months Post Biopsy Has Excellent Sensitivity and Specificity for Favorable 4 Year Renal Outcome in Lupus Nephritis (LN) [Meeting Abstract]
ISI:000411824104073
ISSN: 2326-5205
CID: 2767202
Lupus Nephritis Is Linked to Immunity to an Intestinal Commensal Lachnospiracaea Species [Meeting Abstract]
ISI:000411824104016
ISSN: 2326-5205
CID: 2767262
Preliminary Population-Based Incidence and Prevalence Estimates of Primary Sjogren's Syndrome from the Manhattan Lupus Surveillance Program [Meeting Abstract]
ISI:000411824103006
ISSN: 2326-5205
CID: 2767372
Factors Associated with Cardiac Dysfunction in a Longitudinal Follow-up of Neonatal Lupus [Meeting Abstract]
ISI:000411824106461
ISSN: 2326-5205
CID: 2767522
Pathological Roles By Siglec and Type I Interferons for the Development of Autoimmune Congenital Heart Block [Meeting Abstract]
ISI:000411824106319
ISSN: 2326-5205
CID: 2767542
Interferon-Induced APOL1 over-Expression Causes Autophagic Dysfunction and Mitochondrial Stress in Risk Variant-Carrying Endothelial Cells [Meeting Abstract]
ISI:000411824106317
ISSN: 2326-5205
CID: 2767552
Safety of Hydroxychloroquine Withdrawal in Older Adults with Systemic Lupus Erythematosus [Meeting Abstract]
ISI:000411824106085
ISSN: 2326-5205
CID: 2767562
Exploiting Inhibition of PD1 Signaling in a Murine Model of Anti-SSA/Ro Associated Congenital Heart Block [Meeting Abstract]
ISI:000411824106084
ISSN: 2326-5205
CID: 2767622
Association of Natural Killer Cell Ligand Polymorphism, HLA-C Asn80Lys, with the Development of Anti-SSA/Ro Associated Congenital Heart Block [Meeting Abstract]
ISI:000411824100164
ISSN: 2326-5205
CID: 2767672
Lupus nephritis is linked to immunity to an intestinal commensal lachnospiracaea species [Meeting Abstract]
Background: A transmissible agent has long been suspected in the pathogenesis of SLE. We therefore investigated the potential contribution of the intestinal microbiome to LN.
Method(s): Blood and fecal samples from SLE patients were obtained, unless a patient had selective IgA deficiency, prior cytotoxic drugs, or antibiotics within four months. Fecal 16S rRNA NGS was performed. Sera samples were profiled for autoantibodies. Sera from two independent lupus cohorts were studied for validation.
Result(s): Compared to controls, the intestinal microbiome from SLE patients (N=61) showed decreased species richness diversity. The microbiomes of patients in clinical remission (based on SLEDAI) were most similar to healthy controls, while reductions in taxonomic complexity were most pronounced in those with high disease activity. Notably, SLE patients had an overall 5-fold greater representation of a particular species in the Blautia genus of the Lachnospiracaea family of obligate anaerobic Gram-positive cocci. Abundance of this species significantly correlated with serum IgG to a cell wall moiety from a strain of this species (P=0.002, N=61, Spearman) but not with 7 other strains. There was also a significant correlation between the distribution of SLEDAI scores and levels of these circulating anti-strain IgG antibodies (P=0.02, N=48). Using antigen treated with DNAse/proteinase K, levels of IgG anti-strain antibodies were significantly higher in those with active nephritis at time of sampling compared to SLE without renal activity (Cohort 1 P=0.01 N=48; Cohort 2 P=0.001, N=53, Mann-Whitney). Levels of anti-strain antibodies also significantly correlated with high-titer serum IgG to native DNA (P<0.0001, N=27), and inversely correlated with C3 and C4 (each P<0.01, N=61). High titers of these anti-bacterial antibodies were found in active Class III, IV and V LN.
Conclusion(s): These findings suggest a novel paradigm for the pathogenesis of LN: Specific strains of common intestinal commensal bacteria affect IgG-autoantibody responses in patients with LN. This is reminiscent of post-streptococcal GN, although the postulated intestinal bacterial bloom occurs without clinical infection
Method(s): Blood and fecal samples from SLE patients were obtained, unless a patient had selective IgA deficiency, prior cytotoxic drugs, or antibiotics within four months. Fecal 16S rRNA NGS was performed. Sera samples were profiled for autoantibodies. Sera from two independent lupus cohorts were studied for validation.
Result(s): Compared to controls, the intestinal microbiome from SLE patients (N=61) showed decreased species richness diversity. The microbiomes of patients in clinical remission (based on SLEDAI) were most similar to healthy controls, while reductions in taxonomic complexity were most pronounced in those with high disease activity. Notably, SLE patients had an overall 5-fold greater representation of a particular species in the Blautia genus of the Lachnospiracaea family of obligate anaerobic Gram-positive cocci. Abundance of this species significantly correlated with serum IgG to a cell wall moiety from a strain of this species (P=0.002, N=61, Spearman) but not with 7 other strains. There was also a significant correlation between the distribution of SLEDAI scores and levels of these circulating anti-strain IgG antibodies (P=0.02, N=48). Using antigen treated with DNAse/proteinase K, levels of IgG anti-strain antibodies were significantly higher in those with active nephritis at time of sampling compared to SLE without renal activity (Cohort 1 P=0.01 N=48; Cohort 2 P=0.001, N=53, Mann-Whitney). Levels of anti-strain antibodies also significantly correlated with high-titer serum IgG to native DNA (P<0.0001, N=27), and inversely correlated with C3 and C4 (each P<0.01, N=61). High titers of these anti-bacterial antibodies were found in active Class III, IV and V LN.
Conclusion(s): These findings suggest a novel paradigm for the pathogenesis of LN: Specific strains of common intestinal commensal bacteria affect IgG-autoantibody responses in patients with LN. This is reminiscent of post-streptococcal GN, although the postulated intestinal bacterial bloom occurs without clinical infection
EMBASE:633702312
ISSN: 1533-3450
CID: 4750272
