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Bariatric surgery-induced weight loss reduces B cell activating cytokines and IgG immunoglobulins related to autoimmunity

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Abstract

Background

Obesity is associated with a chronic inflammatory state and autoimmune diseases, but little is known about the role of B cells in this context and the changes in B cell activation factors during obesity and after weight loss. To test whether bariatric-surgery-induced weight loss ameliorates the systemic inflammatory state associated with B cell activation molecules.

Methods

We conducted a prospective observational study in patients treated with bariatric surgery. Anthropometric and body composition measurements were performed preoperatively and at 6 months of follow-up post surgery. The patients were tested for a biochemical profile, plasmatic immunoglobulin G (IgG), cytokines (including specific B cell activating cytokines), and adipokines serum levels

Results

The patients’ weight loss was accounted for mostly by fat mass (52.9%). We observed a significant reduction in total plasmatic IgG levels (p = 0.001), which could be associated with decreased B cell activity. Accordingly, there was a significant decrease in the B cell activating factors such as APRIL, BAFF, and soluble CD40L and a general improvement in the inflammatory markers hs-CRP, IL-1β, IL-12, IL-18, and IFN-γ.

Conclusions

These findings point toward reduced B cell activity after weight loss due to bariatric surgery. Moreover, they could be the initial link among the systemic inflammatory factors, and B cell activation in this inflammatory context that leads to IgG production and, potentially, to autoimmunity in patients with severe obesity.

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References

  1. Castro AM, Macedo-de la Concha LE, Pantoja-Meléndez CA (2017) Low-grade inflammation and its relation to obesity and chronic degenerative diseases. Revista Médica del Hospital General de México 80:101–105. https://doi.org/10.1016/j.hgmx.2016.06.011

    Article  Google Scholar 

  2. Harpsøe MC, Basit S, Andersson M, Nielsen NM, Frisch M, Wohlfahrt J, Nohr EA, Linneberg A, Jess T (2014) Body mass index and risk of autoimmune diseases: a study within the Danish National Birth Cohort. Int J Epidemiol 43:843–855. https://doi.org/10.1093/ije/dyu045

    Article  PubMed  Google Scholar 

  3. Tedeschi SK, Barbhaiya M, Malspeis S, Lu B, Sparks JA, Karlson EW, Willett W, Costenbader KH (2017) Obesity and the risk of systemic lupus erythematosus among women in the Nurses’ Health Studies. Semin Arthritis Rheum 47:376–383. https://doi.org/10.1016/j.semarthrit.2017.05.011

    Article  PubMed  PubMed Central  Google Scholar 

  4. Conway B, Miller RG, Costacou T, Fried L, Kelsey S, Evans RW, Orchard TJ (2009) Adiposity and mortality in type 1 diabetes. Int J Obes (Lond) 33:796–805. https://doi.org/10.1038/ijo.2009.75

    Article  CAS  Google Scholar 

  5. Sparks JA, Halperin F, Karlson JC, Karlson EW, Bermas BL (2015) Impact of bariatric surgery on patients with rheumatoid arthritis. Arthritis Care Res (Hoboken) 67:1619–1626. https://doi.org/10.1002/acr.22629

    Article  CAS  Google Scholar 

  6. Egeberg A, Sørensen JA, Gislason GH, Knop FK, Skov L (2017) Incidence and prognosis of psoriasis and psoriatic arthritis in patients undergoing bariatric surgery. JAMA Surg 152:344–349. https://doi.org/10.1001/jamasurg.2016.4610

    Article  PubMed  Google Scholar 

  7. Cañas CA, Echeverri AF, Ospina FE, Suso J-P, Agualimpia A, Echeverri A, Bonilla-Abadía F, Tobón GJ (2016) Is bariatric surgery a trigger factor for systemic autoimmune diseases? J Clin Rheumatol 22:89–91. https://doi.org/10.1097/RHU.0000000000000363

    Article  PubMed  Google Scholar 

  8. Tobón GJ, Ospina FE, Suso JP, Posso-Osorio I, Echeverri AF, Muñoz-Buitrón E, Martínez J-D, Castaño G-L, Agualimpia A, Bonilla-Abadía F, Dorado E, Cañas CA (2019) Autoantibodies production and immunological abnormalities after bariatric surgery. J Transl Autoimm 2:100024. https://doi.org/10.1016/j.jtauto.2019.100024

    Article  Google Scholar 

  9. McDonnell ME, Ganley-Leal LM, Mehta A, Bigornia SJ, Mott M, Rehman Q, Farb MG, Hess DT, Joseph L, Gokce N, Apovian CM (2012) B lymphocytes in human subcutaneous adipose crown-like structures. Obesity (Silver Spring) 20:1372–1378. https://doi.org/10.1038/oby.2012.54

    Article  CAS  Google Scholar 

  10. Shaikh SR, Haas KM, Beck MA, Teague H (2015) The effects of diet-induced obesity on B cell function. Clin Exp Immunol 179:90–99. https://doi.org/10.1111/cei.12444

    Article  CAS  PubMed  Google Scholar 

  11. Frasca D, Diaz A, Romero M, Thaller S, Blomberg BB (2018) Secretion of autoimmune antibodies in the human subcutaneous adipose tissue. PLoS ONE 13:e0197472. https://doi.org/10.1371/journal.pone.0197472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, Tsui H, Wu P, Davidson MG, Alonso MN, Leong HX, Glassford A, Caimol M, Kenkel JA, Tedder TF, McLaughlin T, Miklos DB, Dosch H-M, Engleman EG (2011) B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med 17:610–617. https://doi.org/10.1038/nm.2353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Camell CD, Günther P, Lee A, Goldberg EL, Spadaro O, Youm Y-H, Bartke A, Hubbard GB, Ikeno Y, Ruddle NH, Schultze J, Dixit VD (2019) Aging induces an Nlrp3 inflammasome-dependent expansion of adipose B cells that impairs metabolic homeostasis. Cell Metab 30:1024–1039.e6. https://doi.org/10.1016/j.cmet.2019.10.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lukens JR, Dixit VD, Kanneganti T-D (2011) Inflammasome activation in obesity-related inflammatory diseases and autoimmunity. Discov Med 12:65–74

    PubMed  PubMed Central  Google Scholar 

  15. Ali MF, Dasari H, Van Keulen VP, Carmona EM (2017) Canonical stimulation of the NLRP3 inflammasome by fungal antigens links innate and adaptive B-lymphocyte responses by modulating IL-1β and IgM production. Front Immunol. https://doi.org/10.3389/fimmu.2017.01504

    Article  PubMed  PubMed Central  Google Scholar 

  16. Enoksson SL, Grasset EK, Hägglöf T, Mattsson N, Kaiser Y, Gabrielsson S, McGaha TL, Scheynius A, Karlsson MCI (2011) The inflammatory cytokine IL-18 induces self-reactive innate antibody responses regulated by natural killer T cells. Proc Natl Acad Sci USA 108:E1399–E1407. https://doi.org/10.1073/pnas.1107830108

    Article  PubMed  PubMed Central  Google Scholar 

  17. Deenick EK, Hasbold J, Hodgkin PD (2005) Decision criteria for resolving isotype switching conflicts by B cells. Eur J Immunol 35:2949–2955. https://doi.org/10.1002/eji.200425719

    Article  CAS  PubMed  Google Scholar 

  18. Frasca D, Riley RL, Blomberg BB (2007) Aging murine B cells have decreased class switch induced by anti-CD40 or BAFF. Exp Gerontol 42:192–203. https://doi.org/10.1016/j.exger.2006.09.003

    Article  CAS  PubMed  Google Scholar 

  19. Müller N, Schulte DM, Hillebrand S, Türk K, Hampe J, Schafmayer C, Brosch M, von Schönfels W, Ahrens M, Zeuner R, Schröder JO, Blüher M, Gutschow C, Freitag-Wolf S, Stelmach-Mardas M, Saggau C, Schreiber S, Laudes M (2014) B Lymphocyte Stimulator (BLyS) is expressed in human adipocytes in vivo and is related to obesity but not to insulin resistance. PLoS ONE 9:e94282. https://doi.org/10.1371/journal.pone.0094282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Schernthaner G-H, Kopp H-P, Krzyzanowska K, Kriwanek S, Koppensteiner R, Schernthaner G (2006) Soluble CD40L in patients with morbid obesity: significant reduction after bariatric surgery. Eur J Clin Invest 36:395–401. https://doi.org/10.1111/j.1365-2362.2006.01649.x

    Article  CAS  PubMed  Google Scholar 

  21. Baena-Fustegueras JA, Pardina E, Balada E, Ferrer R, Catalán R, Rivero J, Casals I, Lecube A, Fort JM, Vargas V, Peinado-Onsurbe J (2013) Soluble CD40 ligand in morbidly obese patients: effect of body mass index on recovery to normal levels after gastric bypass surgery. JAMA Surg 148:151–156. https://doi.org/10.1001/jamasurgery.2013.419

    Article  CAS  PubMed  Google Scholar 

  22. Schneider P (2005) The role of APRIL and BAFF in lymphocyte activation. Curr Opin Immunol 17:282–289. https://doi.org/10.1016/j.coi.2005.04.005

    Article  CAS  PubMed  Google Scholar 

  23. Tran NL, Schneider P, Santiago-Raber M-L (2017) TACI-dependent APRIL signaling maintains autoreactive B cells in a mouse model of systemic lupus erythematosus. Eur J Immunol 47:713–723. https://doi.org/10.1002/eji.201646630

    Article  CAS  PubMed  Google Scholar 

  24. Liu L, Inouye KE, Allman WR, Coleman AS, Siddiqui S, Hotamisligil GS, Akkoyunlu M (2018) TACI-deficient macrophages protect mice against metaflammation and obesity-induced dysregulation of glucose homeostasis. Diabetes 67:1589–1603. https://doi.org/10.2337/db17-1089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kosaraju R, Guesdon W, Crouch MJ, Teague HL, Sullivan EM, Karlsson EA, Schultz-Cherry S, Gowdy K, Bridges LC, Reese LR, Neufer PD, Armstrong M, Reisdorph N, Milner JJ, Beck M, Shaikh SR (2017) B-cell activity is impaired in human and mouse obesity and is responsive to an essential fatty acid upon murine influenza infection. J Immunol 198:4738–4752. https://doi.org/10.4049/jimmunol.1601031

    Article  CAS  PubMed  Google Scholar 

  26. Gardell JL, Parker DC (2017) Antigen-specific transfer of CD40L to antigen-presenting B cells during T cell help. Eur J Immunol 47:41–50. https://doi.org/10.1002/eji.201646504

    Article  CAS  PubMed  Google Scholar 

  27. Poggi M, Engel D, Christ A, Beckers L, Wijnands E, Boon L, Driessen A, Cleutjens J, Weber C, Gerdes N, Lutgens E (2011) CD40L deficiency ameliorates adipose tissue inflammation and metabolic manifestations of obesity in mice. Arterioscler Thromb Vasc Biol 31:2251–2260. https://doi.org/10.1161/ATVBAHA.111.231357

    Article  CAS  PubMed  Google Scholar 

  28. Toczylowski K, Hirnle T, Harasiuk D, Zabielski P, Lewczuk A, Dmitruk I, Ksiazek M, Sulik A, Gorski J, Chabowski A, Baranowski M (2019) Plasma concentration and expression of adipokines in epicardial and subcutaneous adipose tissue are associated with impaired left ventricular filling pattern. J Transl Med 17:310. https://doi.org/10.1186/s12967-019-2060-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Şelli ME, Wick G, Wraith DC, Newby AC (2017) Autoimmunity to HSP60 during diet induced obesity in mice. Int J Obes (Lond) 41:348–351. https://doi.org/10.1038/ijo.2016.216

    Article  CAS  Google Scholar 

  30. Theofilopoulos AN, Kono DH, Baccala R (2017) The multiple pathways to autoimmunity. Nat Immunol 18:716. https://doi.org/10.1038/ni.3731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Giordano A, Murano I, Mondini E, Perugini J, Smorlesi A, Severi I, Barazzoni R, Scherer PE, Cinti S (2013) Obese adipocytes show ultrastructural features of stressed cells and die of pyroptosis. J Lipid Res 54:2423–2436. https://doi.org/10.1194/jlr.M038638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46:2347–2355. https://doi.org/10.1194/jlr.M500294-JLR200

    Article  CAS  PubMed  Google Scholar 

  33. Knudsen C, Combes S, Briens C, Duperray J, Rebours G, Salaun J-M, Travel A, Weissman D, Gidenne T, Oswald IP (2015) Quantitative feed restriction rather than caloric restriction modulates the immune response of growing rabbits. J Nutr 145:483–489. https://doi.org/10.3945/jn.114.197871

    Article  CAS  PubMed  Google Scholar 

  34. Chen X, Kong X (2018) Diabetes remission and relapse after metabolic surgery. J Diabetes Investig 9:1237–1238. https://doi.org/10.1111/jdi.12871

    Article  PubMed  PubMed Central  Google Scholar 

  35. Christ A, Günther P, Lauterbach MAR, Duewell P, Biswas D, Pelka K, Scholz CJ, Oosting M, Haendler K, Baßler K, Klee K, Schulte-Schrepping J, Ulas T, Moorlag SJCFM, Kumar V, Park MH, Joosten LAB, Groh LA, Riksen NP, Espevik T, Schlitzer A, Li Y, Fitzgerald ML, Netea MG, Schultze JL, Latz E (2018) Western diet triggers NLRP3-dependent innate immune reprogramming. Cell 172:162–175.e14. https://doi.org/10.1016/j.cell.2017.12.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sakçak İ, Avşar MF, Hamamcı EO, Bostanoğlu S, Sonışık M, Bostanoğlu A, Erdem NZ, Coşgun E (2010) Comparison of early and late changes in immunoglobulins and acute phase reactants after laparoscopic adjustable gastric banding in patients with morbid obesity. OBES SURG 20:610–615. https://doi.org/10.1007/s11695-009-0061-y

    Article  PubMed  Google Scholar 

  37. Zhang C, Zhang J, Liu W, Chen X, Liu Z, Zhou Z (2019) Improvements in humoral immune function and glucolipid metabolism after laparoscopic sleeve gastrectomy in patients with obesity. Surg Obes Relat Dis 15:1455–1463. https://doi.org/10.1016/j.soard.2019.05.021

    Article  PubMed  Google Scholar 

  38. Obeid S, Wankell M, Charrez B, Sternberg J, Kreuter R, Esmaili S, Ramezani-Moghadam M, Devine C, Read S, Bhathal P, Lopata A, Ahlensteil G, Qiao L, George J, Hebbard L (2017) Adiponectin confers protection from acute colitis and restricts a B cell immune response. J Biol Chem 292:6569–6582. https://doi.org/10.1074/jbc.M115.712646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Chimen M, McGettrick HM, Apta B, Kuravi SJ, Yates CM, Kennedy A, Odedra A, Alassiri M, Harrison M, Martin A, Barone F, Nayar S, Hitchcock JR, Cunningham AF, Raza K, Filer A, Copland DA, Dick AD, Robinson J, Kalia N, Walker LSK, Buckley CD, Nash GB, Narendran P, Rainger GE (2015) Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease. Nat Med 21:467–475. https://doi.org/10.1038/nm.3842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Naylor C, Petri WA (2016) Leptin regulation of immune responses. Trends Mol Med 22:88–98. https://doi.org/10.1016/j.molmed.2015.12.001

    Article  CAS  PubMed  Google Scholar 

  41. Selthofer-Relatić K, Radić R, Stupin A, Šišljagić V, Bošnjak I, Bulj N, Selthofer R, Delić Brkljačić D (2018) Leptin/adiponectin ratio in overweight patients - gender differences. Diab Vasc Dis Res 15:260–262. https://doi.org/10.1177/1479164117752491

    Article  CAS  PubMed  Google Scholar 

  42. Hanna Kazazian N, Wang Y, Roussel-Queval A, Marcadet L, Chasson L, Laprie C, Desnues B, Charaix J, Irla M, Alexopoulou L (2019) Lupus autoimmunity and metabolic parameters are exacerbated upon high fat diet-induced obesity due to TLR7 signaling. Front Immunol 10:2015. https://doi.org/10.3389/fimmu.2019.02015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Opstad TB, Arnesen H, Pettersen AÅ, Seljeflot I (2016) Combined elevated levels of the proinflammatory cytokines IL-18 and IL-12 are associated with clinical events in patients with Coronary Artery Disease: an observational study. Metab Syndr Relat Disord 14:242–248. https://doi.org/10.1089/met.2015.0130

    Article  CAS  PubMed  Google Scholar 

  44. Gaur P, Cebula M, Riehn M, Hillebrand U, Hauser H, Wirth D (2017) Diet induced obesity has an influence on intrahepatic T cell responses. Metab Clin Exp 69:171–176. https://doi.org/10.1016/j.metabol.2017.01.022

    Article  CAS  PubMed  Google Scholar 

  45. Bianchi VE (2018) Weight loss is a critical factor to reduce inflammation. Clin Nutr ESPEN 28:21–35. https://doi.org/10.1016/j.clnesp.2018.08.007

    Article  PubMed  Google Scholar 

  46. Madsen EL, Rissanen A, Bruun JM, Skogstrand K, Tonstad S, Hougaard DM, Richelsen B (2008) Weight loss larger than 10% is needed for general improvement of levels of circulating adiponectin and markers of inflammation in obese subjects: a 3-year weight loss study. Eur J Endocrinol 158:179–187. https://doi.org/10.1530/EJE-07-0721

    Article  CAS  PubMed  Google Scholar 

  47. Magkos F, Fraterrigo G, Yoshino J, Luecking C, Kirbach K, Kelly SC, de Las FL, He S, Okunade AL, Patterson BW, Klein S (2016) Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab 23:591–601. https://doi.org/10.1016/j.cmet.2016.02.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Sacks FM, Bray GA, Carey VJ, Smith SR, Ryan DH, Anton SD, McManus K, Champagne CM, Bishop LM, Laranjo N, Leboff MS, Rood JC, de Jonge L, Greenway FL, Loria CM, Obarzanek E, Williamson DA (2009) Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. https://doi.org/10.1056/NEJMoa0804748

    Article  PubMed  PubMed Central  Google Scholar 

  49. Wadden TA, Neiberg RH, Wing RR, Clark JM, Delahanty LM, Hill JO, Krakoff J, Otto A, Ryan DH, Vitolins MZ, Look AHEAD Research Group (2011) Four-year weight losses in the Look AHEAD study: factors associated with long-term success. Obesity (Silver Spring) 19:1987–1998. https://doi.org/10.1038/oby.2011.230

    Article  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank Noemí García, MSc for the critical discussion of the manuscript and Lucia Villareal for their help with anthropometry measurements.

Funding

This work was partially supported by Cardiovascular Medicine Research Group-Tecnologico de Monterrey 0020CAT131 as well as CONACYT-México Grants 151136 and 256577 (G. G-Rivas) and by the XIGNUX foundation 00220CIE241 (LE-M). R V-C was supported by the Graduate Student Fellowship of CONACYT. This work was submitted in partial fulfillment of the requirements for the PhD degree (RX C-T) for the Doctorate in Clinical Sciences, Tecnologico de Monterrey.

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Author notes

  1. Ricardo X. Cuellar-Tamez and J. Romeo Villarreal-Calderon have contributed equally to this work.

Authors and Affiliations

  1. Tecnologico de Monterrey, Escuela de Medicina Y Ciencias de La Salud, Ave. Morones Prieto 3000, Monterrey, NL, 64710, Mexico

    Ricardo X. Cuellar-Tamez, J. Romeo Villarreal-Calderon, Nestor Rubio-Infante, Elena C. Castillo, Leticia Elizondo-Montemayor & Gerardo García-Rivas

  2. Swiss Hospital, SMG, Monterrey, NL, Mexico

    Manuel García-Garza

  3. Tecnologico de Monterrey, Centro de Investigación en Nutrición Clínica Y Obesidad, Monterrey, NL, Mexico

    Leticia Elizondo-Montemayor

  4. Tecnologico de Monterrey, Centro de Investigación Biomédica, Hospital Zambrano Hellion, TecSalud, 66278, San Pedro Garza García, NL, Mexico

    Gerardo García-Rivas

  5. Tecnologico de Monterrey, Centro de Medicina Funcional, Hospital Zambrano Hellion, TecSalud, 66278, San Pedro Garza García, NL, Mexico

    Gerardo García-Rivas

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  1. Ricardo X. Cuellar-Tamez
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Correspondence to Leticia Elizondo-Montemayor or Gerardo García-Rivas.

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Drs. Cuellar-Tamez, Villarreal-Calderon, Rubio-Infante, Castillo, García-Garza, Elizondo-Montemayor, and García-Rivas have no conflicts of interest or financial ties to disclose.

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Cuellar-Tamez, R.X., Villarreal-Calderon, J.R., Rubio-Infante, N. et al. Bariatric surgery-induced weight loss reduces B cell activating cytokines and IgG immunoglobulins related to autoimmunity. Surg Endosc 35, 5147–5158 (2021). https://doi.org/10.1007/s00464-020-08004-6

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