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Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease
Scher, Jose U; Ubeda, Carles; Artacho, Alejandro; Attur, Mukundan; Isaac, Sandrine; Reddy, Soumya M; Marmon, Shoshana; Neimann, Andrea; Brusca, Samuel; Patel, Tejas; Manasson, Julia; Pamer, Eric G; Littman, Dan R; Abramson, Steven B
OBJECTIVE: To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA). METHODS: High-throughput 16S ribosomal RNA pyrosequencing was utilized to compare the community composition of gut microbiota in patients with PsA (n = 16), patients with psoriasis of the skin (n = 15), and healthy, matched control subjects (n = 17). Samples were further assessed for the presence and levels of fecal and serum secretory IgA (sIgA), proinflammatory proteins, and fatty acids. RESULTS: The gut microbiota observed in patients with PsA and patients with skin psoriasis was less diverse when compared to that in healthy controls. This could be attributed to the reduced presence of several taxa. Samples from both patient groups showed a relative decrease in abundance of Coprococcus species, while samples from PsA patients were also characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA levels and decrease in RANKL levels. Analysis of fatty acids revealed low fecal quantities of hexanoate and heptanoate in both patients with PsA and patients with psoriasis. CONCLUSION: Patients with PsA and patients with skin psoriasis had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had a lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that previously described in patients with inflammatory bowel disease and was associated with changes in specific inflammatory proteins unique to this group, and distinct from that in patients with skin psoriasis and healthy controls. Thus, the role of the gut microbiome in the continuum of psoriasis-PsA pathogenesis and the associated immune response merits further study.
PMCID:4280348
PMID: 25319745
ISSN: 2326-5205
CID: 1453542
Clinical and Imaging Features of Reactive Arthritis in Guatemala City [Meeting Abstract]
Ferrer, Helga Raquel Garcia; Kutzbach, AGarcia; Iraheta, Isa; Scher, Jose U; Von Feldt, Joan; Ogdie-Beatty, Alexis
ISI:000370860201687
ISSN: 2326-5205
CID: 2029012
The Microbiome of Reactive Arthritis in a Guatemalan Cohort [Meeting Abstract]
Ogdie-Beatty, Alexis; Ubeda, Carles; Ferrer, Helga Raquel Garcia; Von Feldt, Joan; Kutzbach, AGarcia; Scher, Jose U
ISI:000370860204368
ISSN: 2326-5205
CID: 2029252
Clinical Improvements in Psoriasis and Psoriatic Arthritis with Surgical Weight Loss [Meeting Abstract]
Sethi, Monica; Ren-Fielding, Christine; Caminer, Ana Clara; Scher, Jose U; Reddy, Soumya M
ISI:000370860201682
ISSN: 2326-5205
CID: 2029522
The Lung Microbiome in Rheumatoid Arthritis and Associated Local/Systemic Autoimmunity [Meeting Abstract]
Scher, Jose U; Joshua, Vijay; Ubeda, Carles; Artacho, Alejandro; Segal, Leopoldo; Catrina, Anca I
ISI:000370860204262
ISSN: 2326-5205
CID: 2029642
Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism
Zanin-Zhorov, Alexandra; Weiss, Jonathan M; Nyuydzefe, Melanie S; Chen, Wei; Scher, Jose U; Mo, Rigen; Depoil, David; Rao, Nishta; Liu, Ben; Wei, Jianlu; Lucas, Sarah; Koslow, Matthew; Roche, Maria; Schueller, Olivier; Weiss, Sara; Poyurovsky, Masha V; Tonra, James; Hippen, Keli L; Dustin, Michael L; Blazar, Bruce R; Liu, Chuan-Ju; Waksal, Samuel D
Rho-associated kinase 2 (ROCK2) regulates the secretion of proinflammatory cytokines and the development of autoimmunity in mice. Data from a phase 1 clinical trial demonstrate that oral administration of KD025, a selective ROCK2 inhibitor, to healthy human subjects down-regulates the ability of T cells to secrete IL-21 and IL-17 by 90% and 60%, respectively, but not IFN-gamma in response to T-cell receptor stimulation in vitro. Pharmacological inhibition with KD025 or siRNA-mediated inhibition of ROCK2, but not ROCK1, significantly diminished STAT3 phosphorylation and binding to IL-17 and IL-21 promoters and reduced IFN regulatory factor 4 and nuclear hormone RAR-related orphan receptor gammat protein levels in T cells derived from healthy subjects or rheumatoid arthritis patients. Simultaneously, treatment with KD025 also promotes the suppressive function of regulatory T cells through up-regulation of STAT5 phosphorylation and positive regulation of forkhead box p3 expression. The administration of KD025 in vivo down-regulates the progression of collagen-induced arthritis in mice via targeting of the Th17-mediated pathway. Thus, ROCK2 signaling appears to be instrumental in regulating the balance between proinflammatory and regulatory T-cell subsets. Targeting of ROCK2 in man may therefore restore disrupted immune homeostasis and have a role in the treatment of autoimmunity.
PMCID:4250132
PMID: 25385601
ISSN: 0027-8424
CID: 1345902
Biomarkers in psoriatic arthritis: recent progress
Chandran, Vinod; Scher, Jose U
Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. About a quarter of patients with psoriasis of the skin will develop PsA, although it is currently challenging-if not impossible-to determine a priori which individuals will progress. Identification of biomarkers for screening, disease activity, joint damage, treatment response and comorbidities are therefore perceived as important clinical needs in the field. Over the last few years, several lines of investigation have advanced our knowledge of new markers for PsA and its outcomes, including genomic, proteomic, cellular and tissue studies. Imaging studies utilizing ultrasonography have been applied to better understand the natural history of the disease. Novel biomarkers, such as soluble proteins and microbiomics, are also being described. Although no biomarker has yet been validated for use in clinical practice, discovery studies are in progress and validation cohorts are being designed. In this report, we review the latest progress in biomarker research in PsA and its potential implications in pathogenesis, diagnosis and therapy.
PMID: 25218735
ISSN: 1534-6307
CID: 2912132
Gender Differences in Disease Activity Accounting for Inflammatory Biomarkers in a Psoriatic Arthritis Routine Care Cohort. [Meeting Abstract]
Reddy, Soumya M; Scher, Jose U; Swearingen, Christopher; Yazici, Yusuf
ISI:000344384903204
ISSN: 2326-5205
CID: 1444032
Elevated Regulatory Mediators and Interferon Gamma Associated Responses, but Not Interferon Alpha, BLyS or IP-10, Accompany High-Titer Anti-Ro Autoantibodies in Asymptomatic Mothers of Children with Neonatal Lupus. [Meeting Abstract]
Izmirly, Peter M; Clancy, Robert M; Munroe, Melissa; Rasmussen, Sara; Saxena, Amit; Scher, Jose U; Thanou, Aikaterini; Kamp, Stan; Merrill, Joan T; Buyon, Jill P; James, Judith
ISI:000344384903229
ISSN: 2326-5205
CID: 1444042
Periodontal disease and subgingival microbiota as contributors for rheumatoid arthritis pathogenesis: modifiable risk factors?
Scher, Jose U; Bretz, Walter A; Abramson, Steven B
PURPOSE OF REVIEW: Since the early 1900s, the role of periodontal disease in the pathogenesis of rheumatoid arthritis has been a matter of intense research. The last decade has witnessed many advances supporting a link between periodontitis, the presence of specific bacterial species (i.e. Porphyromonas gingivalis) and their effects in immune response. This review will examine available evidence on the individuals. RECENT FINDINGS: Epidemiological studies have stressed the commonalities shared by periodontal disease and rheumatoid arthritis. Many groups have focused their attention toward understanding the periodontal microbiota and its alterations in states of health and disease. The presence of circulating antibodies against periodontopathic bacteria and associated inflammatory response has been found in both rheumatoid arthritis (RA) patients and individuals at-risk for disease development. Most recently, the periodontal microbiota of smokers and patients with RA has been elucidated, revealing profound changes in the bacterial communities compared with those of healthy controls. This has led to several small clinical trials of progressive disease treatment as adjuvant for disease-modifying therapy in RA. SUMMARY: Smoking and periodontal disease are emerging risk factors for the development of RA. Epidemiological, clinical, and basic research has further strengthened this association, pointing toward changes in the oral microbiota as possible contributors to systemic inflammation and arthritis.
PMCID:4128331
PMID: 24807405
ISSN: 1040-8711
CID: 972832