This episode walks us through the initial research that paved the way for a game changing therapeutic in ANCA vasculitis, as well as the story of how host Adam J. Brown, MD, finally learned how to spell complement. Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. Intro :10 Welcome :21 Today’s episode :24 So how did we get there? 4:18 How do we start teasing apart the effect of the complement in ANCA vasculitis? 8:13 Discussing and simplifying the mouse model 9:00 Quickly reviewing the complement cascade 12:06 Brought to you by GSK. Consider the long-term impact of disease activity flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com. Taking the puzzle pieces away in the mouse model 17:04 What about the next steps? 22:05 What happens when you block C5a? 25:12 CCX168: Summing up the mouse tale 28:44 In the next episode 30:20 Thanks for listening 30:46 Disclosures: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Brilland B, et al. Autoimmun Rev. 2020;19:102424. Freeley SJ, et al. J Pathol 2016;240:61-71. Haas M, Eustace JA. Kidney Int 2004;65:2145-2152. Huugen D, et al. Kidney Int 2007;71:646-654. Marder SR, et al. Arg. J Immunol. 1985;134:3325-3331. Schreiber A, et al. J Am Soc Nephrol. 2009;20:289-298. Xiao H, et al. Am J Pathol. 2007;170:52-64. Xiao H, et al. J Clin Invest 2002;110:955–963. Xiao H, et al. J Am Soc Nephrol, 2014;25:225–231.

Here I break down the confusing system that is the ire of medical learners who aim to memorize it, only to forget it later. Join me on a medieval journey that will help you visualize this complex system in a way that will stay with you. Brought to you by GSK. Consider the long-term impact of disease activity flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com. Intro :10 Welcome :24 How do you explain the complement system? :44 What is the complement system? 1:39 How does it complement the adaptive immunity? 3:43 Two major aspects of the complement system 4:50 Formation of the membrane attack complex 5:21 Why is this pathway so confusing? 5:55 Why do I have to memorize all of this? 8:33 Let’s talk about the cascades themselves 11:15 Breaking down the three pathways 12:55 Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. The alternative pathway – walking to the beat of its own drum 16:15 A medieval tale of the classic and lectin pathway 22:36 The tale of the alternative pathway 28:00 Summary 31:55 In the next episode 32:40 Disclosures: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Music: The Medieval Banquet by Shane Ivers - https://www.silvermansound.com

We end the year with Leonard Calabrese, DO, giving us a summary of what we’ve learned about COVID-19 from the perspective of a rheumatologist. Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. Intro :10 Calabrese introduction :24 In this episode :43 Nobody has complete control of the literature on COVID-19 1:39 What was ugly about COVID-19? 2:16 What was bad about COVID-19? 4:05 What good came from the COVID-19 pandemic? 7:07 Brought to you by GSK. Consider the long-term impact of disease activity flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com. The good things continued 10:20 JAK inhibitors 11:30 The best outcomes: Vaccines 14:15 Pertinent questions for the rheumatology community 16:45 Recap 20:12 Conclusion 21:41 Disclosures: Calabrese reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum

The completion of the Endocarditis for the Rheumatologist trilogy! This episode focuses on the glomerulonephritis of endocarditis as well as the immunologic abnormalities you can see on labs. Brought to you by GSK. Consider the long-term impact of disease activity flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com. Intro :11 In this episode :22 Recap of previous episodes :39 About episode three 1:00 How labs can give a clue to endocarditis being a culprit 1:23 The immune complex nature of infective endocarditis 6:30 How do you measure immune complex? 9:10 What are the effects of immune complex formation on the organ systems? 12:37 Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. Cryoglobulins and rheumatoid factor in infective endocarditis 15:12 The kidneys and infective endocarditis 16:45 Glomerulonephritis and infective endocarditis 24:15 ANCA-positive vasculitis and infective endocarditis 29:09 A summary of infective endocarditis 32:21 Takeaways 33:28 A preview of next episode 33:48 Conclusion 34:12 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Bayer AS, et al. N Engl J Med. 1976;295:1500-1505. Boils CL, et al. Kidney Int. 2015;87:1241-1249. Forte WC, et al. Arq Bras Cardiol. 2001;76:43-52. Hurwitz D, et al. Clin Exp Immunol. 1975;19:131-141. Langlois V, et al. Medicine (Baltimore). 2016;95:e2564. Levy RL, Hong R. Am J Med. 1973;54:645-652. Ma T-T, et al. PLoS One. 2014;9: https://doi.org/10.1371/journal.pone.0097843. Messias-Reason IL, et al. Clin Exp Immunol. 2002;127:310-315. Petersdorf RG. N Engl J Med. 1976;295:1534-1535. Spain DM, King DW. Ann Intern Med. 1952;36:1086-1089. Williams Jr RC, Kunkel HG. J Clin Invest. 1962;41:666-675. Tire squealing sound effect by Mike Koenig.

This episode focuses on the clinical aspects of endocarditis you can catch in the exam room, emphasizing the joint and skin manifestations, along with some interesting historical insights on Osler nodes and Janeway lesions. Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. Intro :11 In this episode :22 About episode two 2:28 Rheumatologic manifestations of infectious endocarditis 4:28 Musculoskeletal manifestations of infectious endocarditis in the back 5:55 The lack of patterns for infectious endocarditis causing joint pain 9:48 Myalgias and the connection with endocarditis 12:48 The skin and its connection with endocarditis 15:37 What are Janeway lesions 17:13 What are Osler nodes? 19:28 Brought to you by GSK. Consider the long-term impact of disease activity flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com. What causes these lesions? 21:24 Differentiating Osler’s nodes and Janeway lesions 25:20 What are splinter hemorrhages? 28:08 Petechiae and its association to infective endocarditis 31:43 What about leukocytic vasculitis? 33:17 Other puzzle pieces to look for 37:18 A preview of next episode 40:30 Conclusion 42:12 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Chahoud J, et al. Cardiol Rev. 2016;24:230-7. Farrior JB, Silverman ME. Chest. 1976;70:239-43. Godeau P, et al. Rev Med Interne. 1981;2:29-32. Gunson TH, Oliver GF. Australas J Dermatol. 2007;48:251-5. Heffner JE. West J Med. 1979;131:85-91. Loricera J, et al. Clin Exp Rheumatol. 2015;33:36-43. Koslow M, et al. Am J Med. 2014;S0002-9343(14)00188-0.    Murillo O, et al. Infection. 2018;46. Meyers OL, Commerford PJ. Ann of the Rheum Dis. 1977;36:517-519. Parikh SK, et al. J Am Acad Dermatol. 1996;35:767-8. Young J. et al. J R Coll Physicians Lond. 1988;22:240-3.

Infectious endocarditis can present with rheumatic features in 15% to 25% of cases. This series focuses on what a rheumatologist should know about the clinical puzzle of endocarditis. Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com Intro :11 In this episode :22 About episode one 2:33 How did people diagnose infectious endocarditis back in the day? 5:15 What is a Gulstonian Lecture? 6:25 So, who was Dr. Emanuel Libman? 13:33 Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. How Gustav Mahler’s endocarditis diagnosis was made 19:15 The evolution of diagnosing endocarditis 20:45 The story of Alfred S. Reinhart and his self-diagnosis of endocarditis 21:45 Clinical signs and symptoms of endocarditis and how they hold up today 28:00 Recap and a preview of next episode 33:20 Conclusion 35:15 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Flegel KM. CMAJ. 2002;167:1379-1383. Harrison's Principles of Internal Medicine, Nineteenth edition, McGraw-Hill Education, New York, 2015. Levy D. Br Med J (Clin Res Ed). 1986;293:1628-1631. Libman E, Celler HL. Am J Med Sci. 1910;140. Osler W. Br Med J. 1885;1:467-470. Parsons WB Jr, et al. J Am Med Assoc. 1953;153:14-16. Pelletier LL Jr, Petersdorf RG. Medicine (Baltimore). 1977;56:287-313. Ramin S. Hektoen International. 2013;5.

How common is asymptomatic bowel involvement in patients with peripheral or axial SpA? Can we use NSAIDs in these patients? What’s the difference between sulfasalazine and mesalamine? Listen to hear what a rheumatologist should know about IBD! Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. Intro :11 In this episode :20 Let’s start with some basics of IBD 4:11 If a patient has axSpA, what are the chances they’ll develop IBD? 5:14 What about silent disease? 7:32 When should we send our SpA patients to a GI specialist? 11:22 Two medications: budesonide and mesalamine 13:33 Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com This category of drugs – 5-ASA 16:26 NSAIDs 20:02 A look at COX inhibitors 23:06 Selective inhibition with COX-2 seems to be an attractive option for IBD 28:47 Conclusion 29:10 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Altomonte L, et al. Clin Rheumatol. 1994;13:565-570. Dougados M, et al. Joint Bone Spine. 2011;78:598-603. de Winter JJ, et al. Arthritis Res Ther. 2016;18:196. El Miedany Y, et al. Am J Gastroenterol. 2006;101:311-317. Long MD, et al. J Clin Gastroenterol. 2016;50:152-160. Mayberry J. J Gastrointestin Liver Dis. 2013;22:375-377. Miao X-P, et al. Curr Ther Res Clin Exp. 2008;69:181-191. Mielants H, et al. J Rheumatol. 1995;22:2273-2278. Morris AJ, et al. Lancet. 1991;doi: https://doi.org/10.1016/0140-6736(91)91300-J. Redfern JS, Feldman M. Gastroenterology. 1989;96:596-605. Sandborn WJ, et al. Clin Gastroenterol Hepatol. 2006;4:203-211. Stolwijk C, et al. Ann Rheum Dis. 2015;74:65-73. Svartz N. Acta Medica Scandinavica. 1942;doi: https://doi.org/10.1111/j.0954-6820.1942.tb06841.x. Takeuchi K, et al. Clin Gastroenterol Hepatol. 2006;4:196-202. Tanaka K, et al. Eur J Pharmacol. 2008;603:120-132. Van Praet L, et al. Ann Rheum Dis. 2013;72:414-417.

The last episode in the series highlighting how the structure of the antibody was discovered, as well as how a chicken butt was critical in understanding B cell biology. Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com Intro :11 In this episode :15 Recap: What we know about the antibody so far 1:12 Discovering the structure of the antibody 3:34 What else can we learn about the light chain 7:04 An understanding of what these proteins were 9:49 Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. A story about a chicken butt 11:40 Backtracking to 1898 – where do antibodies come from? 16:49 An important paper in 1945 argues the lymphocyte is the antibody maker 18:59 Where is the bursa of Fabricius in humans? 20:46 A study from Australia 21:48 The bone marrow is what did it 23:00 Thanks for listening! 24:48 Disclosures: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Black CA. Immunol Cell Biol. 1997;doi: 10.1038/icb.1997.10. Coons AH, et al. J Exp Med. 1955;102:49-60. Cooper MD. Nat Rev Immunol. 2015;191-197. Edelman GM. J Am Chem Soc. 1959;81:3155-3156. Ehrich WE, Harris TN. Science. 1945;101:28-31. Fagraeus A. J Immunol. 1948;58:1-13. Glick B, et al. Poultry Sci. 1956;35:224-225. Osmond DG, Nossal GJ. Cell Immunol. 1974;13:132-145. Porter RR. Biochem J. 1959;73:119-126. Ryser JE, Vassalli P. J Immunol. 1974;113:719-728.

Learn about the discovery of immunodeficiencies leading to the use of pooled immunoglobulin as therapy, the struggle to use it intravenously and the eventual use in autoimmune disease. Intro :11 In this episode :15 Splitting Part 3 into two episodes :26 Part A of the history of IV Ig and the antibody :53 A recap on Cohn fractionation 2:40 The history and uses of IV Ig 4:30 What led to the recognition and research of primary immunodeficiencies 7:08 How Charles Janeway Sr. paved the way for IV Ig from intramuscular Ig 9:01 What are protein aggregates? 12:54 Understanding the various mechanisms of Ig reactions 15:49 Managing patients with low IgA and anti-IgA antibodies 18:36 How to go from treating immunodeficiency to treating autoimmunity 21:40 The modern understanding and mystery of IV Ig 25:30 Quick summary 26:05 Thanks for listening! 27:30 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Barandun S, et al. Vox Sang. 1962;7:157-174. Eibl MM. Immunol Allergy Clin North Am. 2008;28:737-764, viii. Furusho K, et al. Lancet. 1983;2:1359. Gallagher PE, Buckley RH. J Allergy Clin Immunol. 1982;69:120. Guo Y, et al. Front Immunol. 2018;9:1299. Imbach P, et al. Lancet. 1981;1:1228-31. Intravenous Immunoglobulin: Prevention and Treatment of Disease. NIH Consens Statement Online. 1990;8:1-23. Kustiawan I. PLoS ONE. 2018;13: e0195729. https://doi.org/10.1371/journal.pone.0195729. MRC Working Party on Hypogammaglobulinaemia. Hypogammaglobulinaemia in the United Kingdom. London: Her Majesty’s Stationery Office; 1971. Oransky I. Lancet. 2003;362:409. Sandler SG, et al. Transfus Med Rev. 1995;9:1-8.

Part 2 of this series explores how we began to measure antibody levels and how serotherapy evolved and was used to investigate multiple diseases (I’m looking at you, pneumonia). We’ll also learn how advances in laboratory techniques like electrophoresis paved the way for a better understanding of the antibody. Intro :11 In this episode :15 Recap of Part 1 :22 In this episode :53 The mechanism of action was theoretical 2:30 The story of convalescent serum 6:22 Pneumonia: “The captain of the men of death” 6:58 How culturing was done then 10:56 A big break: Isolating the antibody 14:26 A 30,000-foot look at pneumonia 17:13 Type 1 pneumonia trials 20:20 1918 influenza pandemic 23:31 Measles 27:59 The story of the antibody 30:30 More fun naming conventions 35:25 Cone fractionation 38:35 Quick summary 42:20 Thanks for listening! 44:27 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Black CA. Immunol Cell Biol. 1997;doi: 10.1038/icb.1997.10. Bullowa JGM. JAMA. 1928;90:1354-1358. Cecil RL, Sutliff WD. JAMA. 1928;91:2035-2042. Felton LD. Boston Med Surg J. 1924;190:819-825. Hooper JA. LymphoSign Journal. 2015;2 181-194. Luke TC, et al. Ann Intern Med. 2006;145:599-609. McGuire LW, Redden WR. Am J Public Health. 1918. 741-744. McKhann CF, Chu FT. Am J Dis Child. 1933;45:475-479. Podolsky SH. Am J Public Health. 2005;95:2144-2154. Podolsky SH. J R Soc Med. 2009;102:203-207. Tiselius A, Kabat EA. J Exp Med. 1939;69:119-131.