Top

Published in:

Open Access 29-04-2022 | Immunodeficiency | Original Article

Intravenous Immunoglobulins Promote an Expansion of Monocytic Myeloid-Derived Suppressor Cells (MDSC) in CVID Patients

Authors: Miriam Simón-Fuentes, Silvia Sánchez-Ramón, Lidia Fernández-Paredes, Bárbara Alonso, Kissy Guevara-Hoyer, Miguel A. Vega, Angel L. Corbí, Ángeles Domínguez-Soto

Published in: Journal of Clinical Immunology | Issue 5/2022

Abstract

Common variable immunodeficiency disorders (CVID), the most common primary immune deficiency, includes heterogeneous syndromes characterized by hypogammaglobulinemia and impaired antibody responses. CVID patients frequently suffer from recurrent infections and inflammatory conditions. Currently, immunoglobulin replacement therapy (IgRT) is the first-line treatment to prevent infections and aminorate immune alterations in CVID patients. Intravenous Immunoglobulin (IVIg), a preparation of highly purified poly-specific IgG, is used for treatment of immunodeficiencies as well as for autoimmune and inflammatory disorders, as IVIg exerts immunoregulatory and anti-inflammatory actions on innate and adaptive immune cells. To determine the mechanism of action of IVIg in CVID in vivo, we determined the effect of IVIg infusion on the transcriptome of peripheral blood mononuclear cells from CVID patients, and found that peripheral blood monocytes are primary targets of IVIg in vivo, and that IVIg triggers the acquisition of an anti-inflammatory gene profile in human monocytes. Moreover, IVIg altered the relative proportions of peripheral blood monocyte subsets and enhanced the proportion of CD14⁺ cells with a transcriptional, phenotypic, and functional profile that resembles that of monocytic myeloid-derived suppressor cells (MDSC). Therefore, our results indicate that CD14 + MDSC-like cells might contribute to the immunoregulatory effects of IVIg in CVID and other inflammatory disorders.

Available only for authorised users

Chapel H, Cunningham-Rundles C. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. Br J Haematol. 2009;145:709–27.PubMedPubMedCentralCrossRef

Notarangelo LD, Fischer A, Geha RS, Casanova JL, Chapel H, Conley ME, et al. Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol. 2009;124(6):1161–78.PubMedPubMedCentralCrossRef

Bogaert DJA, Dullaers M, Lambrecht BN, Vermaelen KY, De Baere E, Haerynck F. Genes associated with common variable immunodeficiency: one diagnosis to rule them all? J Med Genet. 2016;53(9):575–90.PubMedCrossRef

Patuzzo G, Barbieri A, Tinazzi E, Veneri D, Argentino G, Moretta F, et al. Autoimmunity and infection in common variable immunodeficiency (CVID). Autoimmun Rev. 2016;15:877–82.PubMedCrossRef

Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119(7):1650–7.PubMedPubMedCentralCrossRef

Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, et al. Common Variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112(2):277–86.PubMedCrossRef

Aspalter RM, Sewell WAC, Dolman K, Farrant J, Webster ADB. Deficiency in circulating natural killer (NK) cell subsets in common variable immunodeficiency and X-linked agammaglobulinaemia. Clin Exp Immunol. 2000;121(3):506–14.PubMedPubMedCentralCrossRef

Litzman J, Vlková M, Pikulová Z, Štikarovská D, Lokaj J. T and B lymphocyte subpopulations and activation/differentiation markers in patients with selective IgA deficiency. Clin Exp Immunol. 2007;147(2):249–54.PubMedPubMedCentralCrossRef

Scott-Taylor TH, Green MR, Raeiszadeh M, Workman S, Webster AD. Defective maturation of dendritic cells in common variable immunodeficiency. Clin Exp Immunol. 2006;145(3):420–7.PubMedPubMedCentralCrossRef

10.

Paquin-Proulx D, Sandberg JK. Persistent immune activation in CVID and the role of IVIg in its suppression. Front Immunol. 2014;5:637. https://doi.org/10.3389/fimmu.2014.00637.

11.

Kaveri SV, Maddur MS, Hegde P, Lacroix-Desmazes S, Bayry J. Intravenous immunoglobulins in immunodeficiencies: more than mere replacement therapy. Clin Exp Immunol. 2011;164:2–5.PubMedPubMedCentralCrossRef

12.

Perez EE, Orange JS, Bonilla F, Chinen J, Chinn IK, Dorsey M, et al. Update on the use of immunoglobulin in human disease: a review of evidence. J Allergy Clin Immunol. 2017;139(3):S1-46.PubMedCrossRef

13.

Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med. 2001;345(10):747–55.PubMedCrossRef

14.

Clynes R. IVIG Therapy: Interfering with Interferon-γ. Immunity. 2007;26(1):4–6.PubMedCrossRef

15.

Gelfand EW. Intravenous immune globulin in autoimmune and inflammatory diseases. N Engl J Med. 2012;367:2015–25.PubMedCrossRef

16.

Schwab I, Nimmerjahn F. Intravenous immunoglobulin therapy: how does IgG modulate the immune system? Nat Rev Immunol. 2013;13:176–89.PubMedCrossRef

17.

Durandy A, Kaveri SV, Kuijpers TW, Basta M, Miescher S, Ravetch JV, et al. Intravenous immunoglobulins-understanding properties and mechanisms. Clin Exp Immunol. 2009;158:2–13.PubMedPubMedCentralCrossRef

18.

Tha-In T, Bayry J, Metselaar HJ, Kaveri SV, Kwekkeboom J. Modulation of the cellular immune system by intravenous immunoglobulin. Trends Immunol. 2008;29:608–15.PubMedCrossRef

19.

Ballow M. The IgG molecule as a biological immune response modifier: mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory disorders. J Allergy Clin Immunol. 2011;127:315–23.PubMedCrossRef

20.

Negi VS, Elluru S, Sibéril S, Graff-Dubois S, Mouthon L, Kazatchkine MD, et al. Intravenous immunoglobulin: an update on the clinical use and mechanisms of action. J Clin Immunol. 2007;27:233–45.PubMedCrossRef

21.

Tjon AS, van Gent R, Geijtenbeek TB, Kwekkeboom J. Differences in anti-inflammatory actions of intravenous immunoglobulin between mice and men: more than meets the eye. Front Immunol. 2015;6:197.PubMedPubMedCentralCrossRef

22.

Corbi AL, Sanchez-Ramon S, Dominguez-Soto A. The potential of intravenous immunoglobulins for cancer therapy: a road that is worth taking? Immunotherapy. 2016;8(5):601–12.PubMedCrossRef

23.

Ben Mkaddem S, Aloulou M, Benhamou M, Monteiro RC. Role of FcγRIIIA (CD16) in IVIg-mediated anti-inflammatory function. J Clin Immunol. 2014;34(SUPPL. 1):S46-50.PubMedCrossRef

24.

Aloulou M, Ben Mkaddem S, Biarnes-Pelicot M, Boussetta T, Souchet H, Rossato E, et al. IgG1 and IVIg induce inhibitory ITAM signaling through FcγRIII controlling inflammatory responses. Blood. 2012;119(13):3084–96.PubMedCrossRef

25.

Luetscher RND, McKitrick TR, Gao C, Mehta AY, McQuillan AM, Kardish R, et al. Unique repertoire of anti-carbohydrate antibodies in individual human serum. Sci Rep. 2020;10(1):15436. https://doi.org/10.1038/s41598-020-71967-y.

26.

Alijotas-Reig J, Esteve-Valverde E, Belizna C, Selva-O’Callaghan A, Pardos-Gea J, Quintana A, et al. Immunomodulatory therapy for the management of severe COVID-19. Beyond the anti-viral therapy: a comprehensive review. Autoimmun Rev. 2020;19:102569.PubMedPubMedCentralCrossRef

27.

Nguyen AA, Habiballah SB, Platt CD, Geha RS, Chou JS, McDonald DR. Immunoglobulins in the treatment of COVID-19 infection: proceed with caution!. Clin Immunol 2020;216:108459. https://doi.org/10.1016/j.clim.2020.108459.

28.

Cao W, Liu X, Bai T, Fan H, Hong K, Song H, et al. High-dose intravenous immunoglobulin as a therapeutic option for deteriorating patients with coronavirus disease 2019. Open Forum Infect Dis. 2020;7(3):1–6.CrossRef

29.

Prete M, Favoino E, Catacchio G, Racanelli V, Perosa F. SARS-CoV-2 infection complicated by inflammatory syndrome. Could high-dose human immunoglobulin for intravenous use (IVIG) be beneficial? Autoimmun Rev. 2020;19(7):102559.PubMedPubMedCentralCrossRef

30.

Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395(10239):1771–8.PubMedPubMedCentralCrossRef

31.

Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395:1607–8.PubMedPubMedCentralCrossRef

32.

Goto R, Inuzuka R, Shindo T, Namai Y, Oda Y, Harita Y, et al. Relationship between post-IVIG IgG levels and clinical outcomes in Kawasaki disease patients: new insight into the mechanism of action of IVIG. Clin Rheumatol. 2020;39(12):3747–55.PubMedCrossRef

33.

Scully M, Singh D, Lown R, Poles A, Solomon T, Levi M, et al. Pathologic antibodies to platelet factor 4 after chAdOx1 nCoV-19 vaccination. N Engl J Med. 2021;384(23):2202–11. https://doi.org/10.1056/NEJMoa2105385.

34.

Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med. 2021;384(22):2092–2101. https://doi.org/10.1056/NEJMoa2104840.

35.

von Hundelshausen P, Lorenz R, Siess W, Weber C. Vaccine-induced immune thrombotic thrombocytopenia (VITT): targeting pathomechanisms with Bruton tyrosine kinase inhibitors. Thromb Haemost. 2021;121(11):1395–9. https://doi.org/10.1055/a-1481-3039.

36.

Dominguez-Soto A, de las Casas-Engel M, Bragado R, Medina-Echeverz J, Aragoneses-Fenoll L, Martin-Gayo E, et al. Intravenous immunoglobulin promotes antitumor responses by modulating macrophage polarization. J Immunol. 2014;193(10):5181–9.PubMedCrossRef

37.

Domínguez-Soto Á, Simón-Fuentes M, de las Casas-Engel M, Cuevas VD, López-Bravo M, Domínguez-Andrés J, et al. IVIg promote cross-tolerance against inflammatory stimuli in vitro and in vivo. J Immunol. 2018;201(1):41–52.PubMedCrossRef

38.

Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, et al. The European Society for Immunodeficiencies (ESID) registry working definitions for the clinical diagnosis of inborn errors of immunity. J Allergy Clin Immunol Pract. 2019;7(6):1763–70.PubMedCrossRef

39.

Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Clin Immunol. 1999;93(3):190–7.PubMedCrossRef

40.

Chapel H, Lucas M, Patel S, Lee M, Cunningham-Rundles C, Resnick E, et al. Confirmation and improvement of criteria for clinical phenotyping in common variable immunodeficiency disorders in replicate cohorts. J Allergy Clin Immunol. 2012;130(5):1197–8. https://doi.org/10.1016/j.jaci.2012.05.046.

41.

Cuevas VD, Anta L, Samaniego R, Orta-Zavalza E, Vladimir de la Rosa J, Baujat G, et al. MAFB determines human macrophage anti-inflammatory polarization: relevance for the pathogenic mechanisms operating in multicentric carpotarsal osteolysis. J Immunol. 2017;198(5):2070–81.PubMedCrossRef

42.

Riera-Borrull M, Cuevas VD, Alonso B, Vega MA, Joven J, Izquierdo E, et al. Palmitate conditions macrophages for enhanced responses toward inflammatory stimuli via JNK activation. J Immunol. 2017;199(11):3858–69.PubMedCrossRef

43.

Nieto C, Rayo I, de las Casas-Engel M, Izquierdo E, Alonso B, Béchade C, et al. Serotonin (5-HT) shapes the macrophage gene profile through the 5-HT 2B –dependent activation of the aryl hydrocarbon receptor. J Immunol. 2020;204(10):2808–17.PubMedCrossRef

44.

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–50.PubMedPubMedCentralCrossRef

45.

Bergenfelz C, Larsson AM, Von Stedingk K, Gruvberger-Saal S, Aaltonen K, Jansson S, et al. Systemic monocytic-MDSCs are generated from monocytes and correlate with disease progression in breast cancer patients. PLoS One. 2015;10(5):e0127028. https://doi.org/10.1371/journal.pone.0127028.

46.

Cappuzzello C, Napolitano M, Arcelli D, Melillo G, Melchionna R, Di Vito L, et al. Gene expression profiles in peripheral blood mononuclear cells of chronic heart failure patients. Physiol Genomics. 2009;38(3):233–40.PubMedCrossRef

47.

Shi M, Chen MS, Sekar K, Tan CK, Ooi LL, Hui KM. A blood-based three-gene signature for the non-invasive detection of early human hepatocellular carcinoma. Eur J Cancer. 2014;50(5):928–36.PubMedCrossRef

48.

Hoechst B, Ormandy LA, Ballmaier M, Lehner F, Krüger C, Manns MP, et al. A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4+CD25+Foxp3+ T cells. Gastroenterology. 2008;135(1):234–43.PubMedCrossRef

49.

Zhou L, Miao K, Yin B, Li H, Fan J, Zhu Y, et al. Cardioprotective role of myeloid-derived suppressor cells in heart failure. Circulation. 2018;138(2):181–97.PubMedCrossRef

50.

Kapellos TS, Bonaguro L, Gemünd I, Reusch N, Saglam A, Hinkley ER, et al. Human monocyte subsets and phenotypes in major chronic inflammatory diseases. Front Immunol. 2019;10:2035. https://doi.org/10.3389/fimmu.2019.02035.

51.

Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity. 2003;19(1):71–82.PubMedCrossRef

52.

Ancuta P, Liu KY, Misra V, Wacleche VS, Gosselin A, Zhou X, et al. Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+ and CD16- monocyte subsets. BMC Genomics. 2009;10:403.PubMedPubMedCentralCrossRef

53.

Schmidl C, Renner K, Peter K, Eder R, Lassmann T, Balwierz PJ, et al. Transcription and enhancer profiling in human monocyte subsets. Blood. 2014;123(17):e90–9. https://doi.org/10.1182/blood-2013-02-484188.

54.

Cavaliere FM, Prezzo A, Conti V, Bilotta C, Pulvirenti F, Iacobini M, et al. Intravenous immunoglobulin replacement induces an in vivo reduction of inflammatory monocytes and retains the monocyte ability to respond to bacterial stimulation in patients with common variable immunodeficiencies. Int Immunopharmacol. 2015;28(1):596–603.PubMedCrossRef

55.

Wong KL, Yeap WH, Tai JJY, Ong SM, Dang TM, Wong SC. The three human monocyte subsets: implications for health and disease. Immunol Res. 2012;53(1–3):41–57.PubMedCrossRef

56.

Veglia F, Perego M, Gabrilovich D. Myeloid-derived suppressor cells coming of age review-article. Nat Immunol. 2018;19:108–19.PubMedPubMedCentralCrossRef

57.

Kumar V, Patel S, Tcyganov E, Gabrilovich DI. The nature of myeloid-derived suppressor cells in the tumor microenvironment. Trends Immunol. 2016;37:208–20.PubMedPubMedCentralCrossRef

58.

Weber R, Fleming V, Hu X, Nagibin V, Groth C, Altevogt P, et al. Myeloid-derived suppressor cells hinder the anti-cancer activity of immune checkpoint inhibitors. Front Immunol. 2018;9:1310.PubMedPubMedCentralCrossRef

59.

Veglia F, Sanseviero E, Gabrilovich DI. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat Rev Immunol. 2021;21(8):485–98. https://doi.org/10.1038/s41577-020-00490-y.

60.

Munn DH, Sharma MD, Baban B, Harding HP, Zhang Y, Ron D, et al. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity. 2005;22(5):633–42.PubMedCrossRef

61.

Bronte V, Brandau S, Chen SH, Colombo MP, Frey AB, Greten TF, et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun. 2016;7:12150. https://doi.org/10.1038/ncomms12150.

62.

Solito S, Marigo I, Pinton L, Damuzzo V, Mandruzzato S, Bronte V. Myeloid-derived suppressor cell heterogeneity in human cancers. Ann N Y Acad Sci. 2014;1319(1):47–65.PubMedCrossRef

63.

Waigel S, Rendon BE, Lamont G, Richie J, Mitchell RA, Yaddanapudi K. MIF inhibition reverts the gene expression profile of human melanoma cell line-induced MDSCs to normal monocytes. Genomics Data. 2016;7:240–2.PubMedPubMedCentralCrossRef

64.

Yaddanapudi K, Rendon BE, Lamont G, Kim EJ, Al Rayyan N, Richie J, et al. MIF is necessary for late-stage melanoma patient MDSC immune suppression and differentiation. Cancer Immunol Res. 2016;4(2):101–12.PubMedCrossRef

65.

Hollen MK, Stortz JA, Darden D, Dirain ML, Nacionales DC, Hawkins RB, et al. Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis. Crit Care. 2019;23(1):355. https://doi.org/10.1186/s13054-019-2628-x.

66.

Yakaboski E, Fuleihan RL, Sullivan KE, Cunningham-Rundles C, Feuille E. Lymphoproliferative disease in CVID: a report of types and frequencies from a US patient registry. J Clin Immunol. 2020;40(3):524–30.PubMedPubMedCentralCrossRef

67.

Fischer A, Provot J, Jais JP, Alcais A, Mahlaoui N, Adoue D, et al. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies. J Allergy Clin Immunol. 2017;140(5):1388-1393.e8.PubMedCrossRef

68.

Fernando SL, Jang HSI, Li J. The immune dysregulation of common variable immunodeficiency disorders. Immunol Lett. 2021;230:21–6.PubMedCrossRef

69.

Hel Z, Huijbregts RPH, Xu J, Nechvatalova J, Vlkova M, Litzman J. Altered serum cytokine signature in common variable immunodeficiency. J Clin Immunol. 2014;34(8):971–8.PubMedPubMedCentralCrossRef

70.

Vlkova M, Chovancova Z, Nechvatalova J, Connelly AN, Davis MD, Slanina P, et al. Neutrophil and granulocytic myeloid-derived suppressor cell–mediated T cell suppression significantly contributes to immune dysregulation in common variable immunodeficiency disorders. J Immunol. 2019;202(1):93–104.PubMedCrossRef

71.

Jørgensen SF, Trøseid M, Kummen M, Anmarkrud JA, Michelsen AE, Osnes LT, et al. Altered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation. Mucosal Immunol. 2016;9(6):1455–65.PubMedCrossRef

72.

Litzman J, Nechvatalova J, Xu J, Ticha O, Vlkova M, Hel Z. Chronic immune activation in common variable immunodeficiency (CVID) is associated with elevated serum levels of soluble CD14 and CD25 but not endotoxaemia. Clin Exp Immunol. 2012;170(3):321–32.PubMedPubMedCentralCrossRef

73.

Barbosa RR, Silva SP, Silva SL, Tendeiro R, Melo AC, Pedro E, et al. Monocyte activation is a feature of common variable immunodeficiency irrespective of plasma lipopolysaccharide levels. Clin Exp Immunol. 2012;169(3):263–72.PubMedPubMedCentralCrossRef

74.

Albin S, Cunningham-Rundles C. An update on the use of immunoglobulin for the treatment of immunodeficiency disorders. Immunotherapy. 2014;6:1113–26.PubMedCrossRef

75.

Paquin-Proulx D, Santos BAN, Carvalho KI, Toledo-Barros M, Barreto de Oliveira AK, Kokron CM, et al. IVIg immune reconstitution treatment alleviates the state of persistent immune activation and suppressed CD4 T cell counts in CVID. PLoS One. 2013;8(10):e75199. https://doi.org/10.1371/journal.pone.0075199.

76.

Zhou J, Zhou Y, Wen J, Sun X, Zhang X. Circulating myeloid-derived suppressor cells predict disease activity and treatment response in patients with immune thrombocytopenia. Braz J Med Biol Res. 2017;50(2):e5637. https://doi.org/10.1590/1414-431X20165637.

77.

Aslam R, Burack WR, Segel GB, McVey M, Spence SA, Semple JW. Intravenous immunoglobulin treatment of spleen cells from patients with immune thrombocytopenia significantly increases the percentage of myeloid-derived suppressor cells. Br J Haematol. 2018;181:262–4.PubMedCrossRef

78.

Janols H, Bergenfelz C, Allaoui R, Larsson A-M, Rydén L, Björnsson S, et al. A high frequency of MDSCs in sepsis patients, with the granulocytic subtype dominating in gram-positive cases. J Leukoc Biol. 2014;96(5):685–93.PubMedCrossRef

79.

Cuenca AG, Delano MJ, Kelly-Scumpia KM, Moreno C, Scumpia PO, LaFace DM, et al. A paradoxical role for myeloid-derived suppressor cells in sepsis and trauma. Mol Med. 2011;17(3–4):281–92.PubMedCrossRef

80.

Siedlar M, Strach M, Bukowska-Strakova K, Lenart M, Szaflarska A, Weglarczyk K, et al. Preparations of intravenous immunoglobulins diminish the number and proinflammatory response of CD14+CD16++ monocytes in common variable immunodeficiency (CVID) patients. Clin Immunol. 2011;139(2):122–32.PubMedCrossRef

81.

Tjon ASW, Metselaar HJ, te Boekhorst PAW, van Hagen PM, Kwekkeboom J. High-dose intravenous immunoglobulin does not reduce the numbers of circulating CD14+CD16++ monocytes in patients with inflammatory disorders. Clin Immunol. 2012;145:11–2.PubMedCrossRef

82.

Siedlar M, Ziegler-Heitbrock L. Commentary to the letter of Tjon et al. Clin Immunol. 2012;145:141.PubMedCrossRef

83.

Katayama K, Matsubara T, Fujiwara M, Koga M, Furukawa S. CD14+CD16+ monocyte subpopulation in Kawasaki disease. Clin Exp Immunol. 2000;121(3):566–70.PubMedPubMedCentralCrossRef

84.

Gonzalez-Dominguez E, Dominguez-Soto A, Nieto C, Luis Flores-Sevilla J, Pacheco-Blanco M, Campos-Pena V, et al. Atypical Activin A and IL-10 production impairs human CD16(+) monocyte differentiation into anti-inflammatory macrophages. J Immunol. 2016;196(3):1327–37.PubMedCrossRef

85.

Maddur MS, Kaveri SV, Bayry J. Circulating normal IgG as stimulator of regulatory T cells: lessons from intravenous immunoglobulin. Trends Immunol. Elsevier Ltd. 2017;38:789–92.PubMedCrossRef

86.

Kaufman GN, Massoud AH, Dembele M, Yona M, Piccirillo CA, Mazer BD. Induction of regulatory T cells by intravenous immunoglobulin: a bridge between adaptive and innate immunity. Front Immunol. 2015;6:469. https://doi.org/10.3389/fimmu.2015.00469.

87.

Trinath J, Hegde P, Sharma M, Maddur MS, Rabin M, Vallat JM, et al. Intravenous immunoglobulin expands regulatory T cells via induction of cyclooxygenase-2-dependent prostaglandin E2 in human dendritic cells. Blood. 2013;122(8):1419–27.PubMedCrossRef

88.

Tjon ASW, Tha-In T, Metselaar HJ, van Gent R, van der Laan LJW, Groothuismink ZMA, et al. Patients treated with high-dose intravenous immunoglobulin show selective activation of regulatory T cells. Clin Exp Immunol. 2013;173(2):259–67.PubMedPubMedCentralCrossRef

89.

Wang SC, Yang KD, Lin CY, Huang AY, Hsiao CC, Lin MT, et al. Intravenous immunoglobulin therapy enhances suppressive regulatory T cells and decreases innate lymphoid cells in children with immune thrombocytopenia. Pediatr Blood Cancer. 2020;67(2):e28075. https://doi.org/10.1002/pbc.28075.

90.

Zhang G, Wang Q, Song Y, Cheng P, Xu R, Feng X, et al. Intravenous immunoglobulin promotes the proliferation of CD4+CD25+ Foxp3+ regulatory T cells and the cytokines secretion in patients with Guillain-Barré syndrome in vitro. J Neuroimmunol. 2019;336:577042. https://doi.org/10.1016/j.jneuroim.2019.577042.

91.

Xu W, Ren M, Ghosh S, Qian K, Luo Z, Zhang A, et al. Defects of CTLA-4 are associated with regulatory T cells in myasthenia gravis implicated by intravenous immunoglobulin therapy. Mediat Inflamm. 2020;2020:3645157. https://doi.org/10.1155/2020/3645157.

92.

Massoud AH, Kaufman GN, Xue D, Béland M, Dembele M, Piccirillo CA, et al. Peripherally generated Foxp3 + regulatory T cells mediate the immunomodulatory effects of IVIg in allergic airways disease. J Immunol. 2017;198(7):2760–71.PubMedCrossRef

93.

Hirabayashi Y, Takahashi Y, Xu Y, Akane K, Villalobos IB, Okuno Y, et al. Lack of CD4+CD25+FOXP3+ regulatory T cells is associated with resistance to intravenous immunoglobulin therapy in patients with Kawasaki disease. Eur J Pediatr. 2013;172(6):833–7.PubMedCrossRef

94.

Ephrem A, Chamat S, Miquel C, Fisson S, Mouthon L, Caligiuri G, et al. Expansion of CD4+CD25+ regulatory T cells by intravenous immunoglobulin: a critical factor in controlling experimental autoimmune encephalomyelitis. Blood. 2008;111(2):715–22.PubMedCrossRef

95.

Maddur MS, Stephen-Victor E, Das M, Prakhar P, Sharma VK, Singh V, et al. Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy. J Neuroinflamm 2017;14(1):58. https://doi.org/10.1186/s12974-017-0818-5.

96.

Zoso A, Mazza EMC, Bicciato S, Mandruzzato S, Bronte V, Serafini P, et al. Human fibrocytic myeloid-derived suppressor cells express IDO and promote tolerance via Treg-cell expansion. Eur J Immunol. 2014;44(11):3307–19.PubMedCrossRef

97.

Serafini P, Mgebroff S, Noonan K, Borrello I. Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res. 2008;68(13):5439–49.PubMedPubMedCentralCrossRef

98.

Groth C, Hu X, Weber R, Fleming V, Altevogt P, Utikal J, et al. Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression. Br J Cancer. Nature Publishing Group. 2019;120:16–25.PubMedCrossRef

99.

Hatziioannou A, Alissafi T, Verginis P. Myeloid-derived suppressor cells and T regulatory cells in tumors: unraveling the dark side of the force. J Leukoc Biol. 2017;102(2):407–21.PubMedCrossRef

100.

Siret C, Collignon A, Silvy F, Robert S, Cheyrol T, André P, et al. Deciphering the crosstalk between myeloid-derived suppressor cells and regulatory T cells in pancreatic ductal adenocarcinoma. Front Immunol. 2020;10:3070. https://doi.org/10.3389/fimmu.2019.03070.

101.

Schlecker E, Stojanovic A, Eisen C, Quack C, Falk CS, Umansky V, et al. Tumor- infiltrating monocytic myeloid-derived suppressor cells mediate CCR5-dependent recruitment of regulatory T cells favoring tumor growth. J Immunol. 2012;189(12):5602–11.PubMedCrossRef

102.

Hauck F, Gennery AR, Seidel MG. Editorial: The relationship between cancer predisposition and primary immunodeficiency. Front Immunol. 2019;10:1781. https://doi.org/10.3389/fimmu.2019.01781.

Title: Intravenous Immunoglobulins Promote an Expansion of Monocytic Myeloid-Derived Suppressor Cells (MDSC) in CVID Patients
Authors: Miriam Simón-Fuentes
Silvia Sánchez-Ramón
Lidia Fernández-Paredes
Bárbara Alonso
Kissy Guevara-Hoyer
Miguel A. Vega
Angel L. Corbí
Ángeles Domínguez-Soto
Publication date: 29-04-2022
Publisher: Springer US
Keyword: Immunodeficiency
Published in: Journal of Clinical Immunology / Issue 5/2022
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-022-01277-7

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2022

Genetic Testing in Egyptian Patients with Inborn Errors of Immunity: a Single-Center Experience

A High-Throughput Amplicon Screen for Somatic UBA1 Variants in Cytopenic and Giant Cell Arteritis Cohorts

Development of Laboratory Parameters-Based Formulas in Predicting Short Outcomes for Adult Hemophagocytic Lymphohistiocytosis Patients with Different Underlying Diseases

Copy Number Analysis in a Large Cohort Suggestive of Inborn Errors of Immunity Indicates a Wide Spectrum of Relevant Chromosomal Losses and Gains

Correction to: Dexamethasone Treatment for COVID-19-Related Lung Injury in an Adult with WHIM Syndrome

The Impact of SARS-CoV-2 Infection in Patients with Inborn Errors of Immunity: the Experience of the Italian Primary Immunodeficiencies Network (IPINet)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage