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Supplemental Material for Paradoxical Effects of Depression on Psoriatic Arthritis Outcomes in a Combined Psoriasis-Psoriatic Arthritis Center by Rebecca H. Haberman, MD, Seungha Um, PhD, Sydney Catron, BS, Alan Chen, BA, Eileen Lydon, NP, Malavikalakshmi Attur, MD, Andrea L. Neimann, MD, Soumya Reddy, MD, Andrea Troxel, ScD, Samrachana Adhikari, PhD and Jose U. Scher, MD in Journal of Psoriasis and Psoriatic Arthritis®

To characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome of psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients.

Supplemental Material, Appendix_4_Study_Selection_Process for 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis by Jasvinder A. Singh, Gordon Guyatt, Alexis Ogdie, Dafna D. Gladman, Chad Deal, Atul Deodhar, Maureen Dubreuil, Jonathan Dunham, M. Elaine Husni, Sarah Kenny, Jennifer Kwan-Morley, Janice Lin, Paula Marchetta, Philip J. Mease, Joseph F. Merola, Julie Miner, Christopher T. Ritchlin, Bernadette Siaton, Benjamin J. Smith, Abby S. Van Voorhees, Anna Helena Jonsson, Amit Aakash Shah, Nancy Sullivan, Marat Turgunbaev, Laura C. Coates, Alice Gottlieb, Marina Magrey, W. Benjamin Nowell, Ana-Maria Orbai, Soumya M. Reddy, Jose U. Scher, Evan Siegel, Michael Siegel, Jessica A. Walsh, Amy S. Turner, and James Reston in Journal of Psoriasis and Psoriatic Arthritis

Supplemental Material, Singh_ART40726_Supplementary_Appendix_1_Methods for 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis by Jasvinder A. Singh, Gordon Guyatt, Alexis Ogdie, Dafna D. Gladman, Chad Deal, Atul Deodhar, Maureen Dubreuil, Jonathan Dunham, M. Elaine Husni, Sarah Kenny, Jennifer Kwan-Morley, Janice Lin, Paula Marchetta, Philip J. Mease, Joseph F. Merola, Julie Miner, Christopher T. Ritchlin, Bernadette Siaton, Benjamin J. Smith, Abby S. Van Voorhees, Anna Helena Jonsson, Amit Aakash Shah, Nancy Sullivan, Marat Turgunbaev, Laura C. Coates, Alice Gottlieb, Marina Magrey, W. Benjamin Nowell, Ana-Maria Orbai, Soumya M. Reddy, Jose U. Scher, Evan Siegel, Michael Siegel, Jessica A. Walsh, Amy S. Turner, and James Reston in Journal of Psoriasis and Psoriatic Arthritis

Supplemental Material, Appendixs5_revised for 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis by Jasvinder A. Singh, Gordon Guyatt, Alexis Ogdie, Dafna D. Gladman, Chad Deal, Atul Deodhar, Maureen Dubreuil, Jonathan Dunham, M. Elaine Husni, Sarah Kenny, Jennifer Kwan-Morley, Janice Lin, Paula Marchetta, Philip J. Mease, Joseph F. Merola, Julie Miner, Christopher T. Ritchlin, Bernadette Siaton, Benjamin J. Smith, Abby S. Van Voorhees, Anna Helena Jonsson, Amit Aakash Shah, Nancy Sullivan, Marat Turgunbaev, Laura C. Coates, Alice Gottlieb, Marina Magrey, W. Benjamin Nowell, Ana-Maria Orbai, Soumya M. Reddy, Jose U. Scher, Evan Siegel, Michael Siegel, Jessica A. Walsh, Amy S. Turner, and James Reston in Journal of Psoriasis and Psoriatic Arthritis

Supplemental Material, Appendix_2_Panel,_Teams_Involved for 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis by Jasvinder A. Singh, Gordon Guyatt, Alexis Ogdie, Dafna D. Gladman, Chad Deal, Atul Deodhar, Maureen Dubreuil, Jonathan Dunham, M. Elaine Husni, Sarah Kenny, Jennifer Kwan-Morley, Janice Lin, Paula Marchetta, Philip J. Mease, Joseph F. Merola, Julie Miner, Christopher T. Ritchlin, Bernadette Siaton, Benjamin J. Smith, Abby S. Van Voorhees, Anna Helena Jonsson, Amit Aakash Shah, Nancy Sullivan, Marat Turgunbaev, Laura C. Coates, Alice Gottlieb, Marina Magrey, W. Benjamin Nowell, Ana-Maria Orbai, Soumya M. Reddy, Jose U. Scher, Evan Siegel, Michael Siegel, Jessica A. Walsh, Amy S. Turner, and James Reston in Journal of Psoriasis and Psoriatic Arthritis

Supplemental Material, Appendix_6_Strong_Recommendations.docx for 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis by Jasvinder A. Singh, Gordon Guyatt, Alexis Ogdie, Dafna D. Gladman, Chad Deal, Atul Deodhar, Maureen Dubreuil, Jonathan Dunham, M. Elaine Husni, Sarah Kenny, Jennifer Kwan-Morley, Janice Lin, Paula Marchetta, Philip J. Mease, Joseph F. Merola, Julie Miner, Christopher T. Ritchlin, Bernadette Siaton, Benjamin J. Smith, Abby S. Van Voorhees, Anna Helena Jonsson, Amit Aakash Shah, Nancy Sullivan, Marat Turgunbaev, Laura C. Coates, Alice Gottlieb, Marina Magrey, W. Benjamin Nowell, Ana-Maria Orbai, Soumya M. Reddy, Jose U. Scher, Evan Siegel, Michael Siegel, Jessica A. Walsh, Amy S. Turner, and James Reston in Journal of Psoriasis and Psoriatic Arthritis

Supplemental Material, Appendix_1_Methods for 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis by Jasvinder A. Singh, Gordon Guyatt, Alexis Ogdie, Dafna D. Gladman, Chad Deal, Atul Deodhar, Maureen Dubreuil, Jonathan Dunham, M. Elaine Husni, Sarah Kenny, Jennifer Kwan-Morley, Janice Lin, Paula Marchetta, Philip J. Mease, Joseph F. Merola, Julie Miner, Christopher T. Ritchlin, Bernadette Siaton, Benjamin J. Smith, Abby S. Van Voorhees, Anna Helena Jonsson, Amit Aakash Shah, Nancy Sullivan, Marat Turgunbaev, Laura C. Coates, Alice Gottlieb, Marina Magrey, W. Benjamin Nowell, Ana-Maria Orbai, Soumya M. Reddy, Jose U. Scher, Evan Siegel, Michael Siegel, Jessica A. Walsh, Amy S. Turner, and James Reston in Journal of Psoriasis and Psoriatic Arthritis

Supplemental Material, Singh_ART40726_Supplementary_Appendix_4_Study_Selection_Process for 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis by Jasvinder A. Singh, Gordon Guyatt, Alexis Ogdie, Dafna D. Gladman, Chad Deal, Atul Deodhar, Maureen Dubreuil, Jonathan Dunham, M. Elaine Husni, Sarah Kenny, Jennifer Kwan-Morley, Janice Lin, Paula Marchetta, Philip J. Mease, Joseph F. Merola, Julie Miner, Christopher T. Ritchlin, Bernadette Siaton, Benjamin J. Smith, Abby S. Van Voorhees, Anna Helena Jonsson, Amit Aakash Shah, Nancy Sullivan, Marat Turgunbaev, Laura C. Coates, Alice Gottlieb, Marina Magrey, W. Benjamin Nowell, Ana-Maria Orbai, Soumya M. Reddy, Jose U. Scher, Evan Siegel, Michael Siegel, Jessica A. Walsh, Amy S. Turner, and James Reston in Journal of Psoriasis and Psoriatic Arthritis

Supplemental Material, Appendix_3_PsA_Search_Strategies for 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis by Jasvinder A. Singh, Gordon Guyatt, Alexis Ogdie, Dafna D. Gladman, Chad Deal, Atul Deodhar, Maureen Dubreuil, Jonathan Dunham, M. Elaine Husni, Sarah Kenny, Jennifer Kwan-Morley, Janice Lin, Paula Marchetta, Philip J. Mease, Joseph F. Merola, Julie Miner, Christopher T. Ritchlin, Bernadette Siaton, Benjamin J. Smith, Abby S. Van Voorhees, Anna Helena Jonsson, Amit Aakash Shah, Nancy Sullivan, Marat Turgunbaev, Laura C. Coates, Alice Gottlieb, Marina Magrey, W. Benjamin Nowell, Ana-Maria Orbai, Soumya M. Reddy, Jose U. Scher, Evan Siegel, Michael Siegel, Jessica A. Walsh, Amy S. Turner, and James Reston in Journal of Psoriasis and Psoriatic Arthritis

Supplemental Material, Singh_ART40726_Supplementary_Appendix_2_Panel,_Teams_Involved for 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis by Jasvinder A. Singh, Gordon Guyatt, Alexis Ogdie, Dafna D. Gladman, Chad Deal, Atul Deodhar, Maureen Dubreuil, Jonathan Dunham, M. Elaine Husni, Sarah Kenny, Jennifer Kwan-Morley, Janice Lin, Paula Marchetta, Philip J. Mease, Joseph F. Merola, Julie Miner, Christopher T. Ritchlin, Bernadette Siaton, Benjamin J. Smith, Abby S. Van Voorhees, Anna Helena Jonsson, Amit Aakash Shah, Nancy Sullivan, Marat Turgunbaev, Laura C. Coates, Alice Gottlieb, Marina Magrey, W. Benjamin Nowell, Ana-Maria Orbai, Soumya M. Reddy, Jose U. Scher, Evan Siegel, Michael Siegel, Jessica A. Walsh, Amy S. Turner, and James Reston in Journal of Psoriasis and Psoriatic Arthritis

Supplemental Material, Singh_ART40726_Supplementary_Appendix_3_PsA_Search_Strategies for 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis by Jasvinder A. Singh, Gordon Guyatt, Alexis Ogdie, Dafna D. Gladman, Chad Deal, Atul Deodhar, Maureen Dubreuil, Jonathan Dunham, M. Elaine Husni, Sarah Kenny, Jennifer Kwan-Morley, Janice Lin, Paula Marchetta, Philip J. Mease, Joseph F. Merola, Julie Miner, Christopher T. Ritchlin, Bernadette Siaton, Benjamin J. Smith, Abby S. Van Voorhees, Anna Helena Jonsson, Amit Aakash Shah, Nancy Sullivan, Marat Turgunbaev, Laura C. Coates, Alice Gottlieb, Marina Magrey, W. Benjamin Nowell, Ana-Maria Orbai, Soumya M. Reddy, Jose U. Scher, Evan Siegel, Michael Siegel, Jessica A. Walsh, Amy S. Turner, and James Reston in Journal of Psoriasis and Psoriatic Arthritis

Supplemental Material, Singh_ART40726_Supplementary_Appendix_5_Evidence_Report for 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis by Jasvinder A. Singh, Gordon Guyatt, Alexis Ogdie, Dafna D. Gladman, Chad Deal, Atul Deodhar, Maureen Dubreuil, Jonathan Dunham, M. Elaine Husni, Sarah Kenny, Jennifer Kwan-Morley, Janice Lin, Paula Marchetta, Philip J. Mease, Joseph F. Merola, Julie Miner, Christopher T. Ritchlin, Bernadette Siaton, Benjamin J. Smith, Abby S. Van Voorhees, Anna Helena Jonsson, Amit Aakash Shah, Nancy Sullivan, Marat Turgunbaev, Laura C. Coates, Alice Gottlieb, Marina Magrey, W. Benjamin Nowell, Ana-Maria Orbai, Soumya M. Reddy, Jose U. Scher, Evan Siegel, Michael Siegel, Jessica A. Walsh, Amy S. Turner, and James Reston in Journal of Psoriasis and Psoriatic Arthritis

Perturbation of commensal intestinal microbiota has been associated with several autoimmune diseases. Mice deficient in interleukin-1 receptor antagonist (Il1rn −/− mice) spontaneously develop autoimmune arthritis and are susceptible to other autoimmune diseases such as psoriasis, diabetes, and encephalomyelitis; however, the mechanisms of increased susceptibility to these autoimmune phenotypes are poorly understood. We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) in regulation of commensal intestinal microbiota, and assessed the involvement of microbiota subsets and innate and adaptive mucosal immune responses that underlie the development of spontaneous arthritis in Il1rn −/− mice. Using high-throughput 16S rRNA gene sequencing, we show that IL-1Ra critically maintains the diversity and regulates the composition of intestinal microbiota in mice. IL-1Ra deficiency reduced the intestinal microbial diversity and richness, and caused specific taxonomic alterations characterized by overrepresented Helicobacter and underrepresented Ruminococcus and Prevotella. Notably, the aberrant intestinal microbiota in IL1rn −/− mice specifically potentiated IL-17 production by intestinal lamina propria (LP) lymphocytes and skewed the LP T cell balance in favor of T helper 17 (Th17) cells, an effect transferable to WT mice by fecal microbiota. Importantly, LP Th17 cell expansion and the development of spontaneous autoimmune arthritis in IL1rn −/− mice were attenuated under germ-free condition. Selective antibiotic treatment revealed that tobramycin-induced alterations of commensal intestinal microbiota, i.e., reduced Helicobacter, Flexispira, Clostridium, and Dehalobacterium, suppressed arthritis in IL1rn −/− mice. The arthritis phenotype in IL1rn −/− mice was previously shown to depend on Toll-like receptor 4 (TLR4). Using the ablation of both IL-1Ra and TLR4, we here show that the aberrations in the IL1rn −/− microbiota are partly TLR4-dependent. We further identify a role for TLR4 activation in the intestinal lamina propria production of IL-17 and cytokines involved in Th17 differentiation preceding the onset of arthritis. These findings identify a critical role for IL1Ra in maintaining the natural diversity and composition of intestinal microbiota, and suggest a role for TLR4 in mucosal Th17 cell induction associated with the development of autoimmune disease in mice.

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.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.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.