CASE REPORT

Introducing the tolerogenic macrophage therapy as an alternative approach to manage systemic lupus erythematosus: a case series

Terawan Agus Putranto , Djoko Wibisono, Nyoto Widyo Astoro, Martina Lily Yana, Endra Tri Prabowo, Denny Irwansyah, Nurhadiyanta Nurhadiyanta, Yudo Rantung, Taruna Ikrar, Fred Fandrich

Terawan Agus Putranto
The Indonesia Army Medical Science Institute, Jakarta, Indonesia Department of Cellcure, RSPAD Gatot Soebroto, Jakarta, Indonesia. Email: [email protected]

Djoko Wibisono
Department of Cellcure, RSPAD Gatot Soebroto, Jakarta, Indonesia

Nyoto Widyo Astoro
Department of Cellcure, RSPAD Gatot Soebroto, Jakarta, Indonesia

Martina Lily Yana
Department of Cellcure, RSPAD Gatot Soebroto, Jakarta, Indonesia

Endra Tri Prabowo
Department of Cellcure, RSPAD Gatot Soebroto, Jakarta, Indonesia

Denny Irwansyah
Department of Cellcure, RSPAD Gatot Soebroto, Jakarta, Indonesia

Nurhadiyanta Nurhadiyanta
Department of Cellcure, RSPAD Gatot Soebroto, Jakarta, Indonesia

Yudo Rantung
The Indonesia Army Medical Science Institute, Jakarta, Indonesia

Taruna Ikrar
The Indonesia Army Medical Science Institute, Jakarta, Indonesia Department of Cellcure, RSPAD Gatot Soebroto, Jakarta, Indonesia Pacific Health Sciences University, California, United States of America

Fred Fandrich
Department of Cellcure, RSPAD Gatot Soebroto, Jakarta, Indonesia
Online First: December 01, 2019 | Cite this Article
Putranto, T., Wibisono, D., Astoro, N., Yana, M., Prabowo, E., Irwansyah, D., Nurhadiyanta, N., Rantung, Y., Ikrar, T., Fandrich, F. 2019. Introducing the tolerogenic macrophage therapy as an alternative approach to manage systemic lupus erythematosus: a case series. Bali Medical Journal 8(3). DOI:10.15562/bmj.v8i3.1621


Introduction: Systemic Lupus Erythematosus (SLE) has been quite an enigma in medicine. The possibility of the host own defense mechanism attacking itself is still quite difficult to understand. Patients who suffer from this disease tend to have a problem in their qualities of life, especially as the majority affect female in their productive ages. Conservative therapy to manage this disease is widely developed and implemented. Since the known therapies have several side effects and limitation, a need to develop a new strategy that can re-establish the “tolerance” mechanism of our immune system is increasingly needed. Immunotherapy is already a promising field in the strategy against autoimmune cases. In our facility, we developed immunotherapy called ToM (Tolerogenic Macrophage) which similar to Mreg (Regulatory Macrophage) in order to utilise the “tolerance” ability of this immune apparatus.

Case: In this study, we present 2 cases of female patients who suffer from SLE, which underwent ToM Therapy in our Cellcure facility in RSPAD Gatot Soebroto Jakarta-Indonesia. After the procedure the patient was monitored one month and one year. Clinical and control parameter such as ANA (IF) and ANA profile was examined again in both patients to measure the effect of this therapy. The ANA titer and the titer of specific antibodies such as dsDNA, Nucleosomes and Histones results show significant reduction, accompanied by the improvement of the symptoms.

Conclusion: ToM Therapy seems to have a good efficacy as immunotherapy for SLE. Further study needed to establish this approach.

References

Klemperer P., Pollack A., Baehr G. Pathology of disseminated lupus erythematosus. Arch Pathol. 1941;32(569):631.

Miller S.D., Turley D.M., Podojil J.R. Antigen-specific tolerance strategies for the prevention and treatment of autoimmune disease. Nat Rev Immunol. 2007;7(9):665–77.

Lahita R.G., Leon Bradlow H., Kunkel H.G., Fishman J. Alterations of estrogen metabolism in systemic lupus erythematosus. Arthritis Rheum. 1979;22(11):1195–8.

Lewis M.J., Jawad A.S. The effect of ethnicity and genetic ancestry on the epidemiology, clinical features and outcome of systemic lupus erythematosus. Rheumatology. 2017;Apr 1(Suppl_1):i67–77.

Pons-Estel G.J., Wojdyla D., McGwin G., Magder L.S., Petri M.A., Pons-Estel B.A., et al. The American College of Rheumatology and the Systemic Lupus International Collaborating Clinics Classification criteria for systemic lupus erythematosus in two multiethnic cohorts: a commentary. Lupus. 2013;23(1):3–9.

Rahman A., Isenberg D.A. Systemic Lupus Erythematosus. N Engl J Med. 2008;358(9):929–39.

Oelke K., Richardson B. Pathogenesis of lupus. Arthritis Rheum. 2002;47(3):343–5.

Yoshimi R., Ueda A., Ozato K., Ishigatsubo Y. Clinical and Pathological Roles of Ro/SSA Autoantibody System. Clin Dev Immunol. 2012;2012:1–12.

Arnett F.C., Reveille J.D., Moutsopoulos H.M., Georgescu L., Elkon K.B. Ribosomal P autoantibodies in systemic lupus erythematosus. Frequencies in different ethnic groups and clinical and immunogenetic associations. Arthritis Rheum. 1996;39(11):1833–9.

Isshi K., Hirohata S. Association of anti–ribosomal P protein antibodies with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 1996;39(9):1483–90.

Herrmann M., Voll R.E., Zoller O.M., Hagenhofer M., Ponner B.B., Kalden J.R. Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum. 1998;41(7):1241–50.

Leuchten N., Hoyer A., Brinks R., Schoels M., Schneider M., Smolen J., et al. Performance of Antinuclear Antibodies for Classifying Systemic Lupus Erythematosus: A Systematic Literature Review and Meta-Regression of Diagnostic Data. Arthritis Care Res (Hoboken). 2018;70(3):428–38.

Cozzani E., Drosera M., Gasparini G., Parodi A. Serology of Lupus Erythematosus: Correlation between Immunopathological Features and Clinical Aspects. Autoimmune Dis. 2014;2014:1–13.

Ghrahani R., Sapartini G., Setiabudiawan B. Antibodi Antinuklear sebagai Faktor Risiko Keterlibatan Sistem Hematologi Lupus Eritematosus Sistemik pada Anak. Maj Kedokt Bandung. 2015;47(2):124–8.

Wiryadana K.A., Supadmanaba I.G.P., Samatra I.D.P.G. Progress and potential roles blood biomarkers of ischemic stroke in clinical setting. Indones J Biomed Sci. 2017;11(2):19–29.

Kumar Y., Bhatia A., Minz R. Antinuclear antibodies and their detection methods in diagnosis of connective tissue diseases: a journey revisited. Diagn Pathol. 2009;4(1):1–10.

Yuriawantini, Suryana K. Aspek Imunologi SLE. J Penyakit Dalam. 2007;232–9.

SHELDON J. Laboratory testing in autoimmune rheumatic diseases. Best Pract Res Clin Rheumatol. 2004;18(3):249–69.

Fries J.F. The Assessment of Disability: from first to future principles. Rheumatology. 1983;XXII(suppl 1):48–58.

TSOKOS G. Overview of cellular immune function in systemic lupus erythematosus [Internet]. Systemic Lupus Erythematosus. Elsevier; 2004. p. 29–92.

Lopez R., Davidson J.E., Beeby M.D., Egger P.J., Isenberg D.A. Lupus disease activity and the risk of subsequent organ damage and mortality in a large lupus cohort. Rheumatology. 2011;51(3):491–8.

Lo M.S., Tsokos G.C. Treatment of systemic lupus erythematosus: new advances in targeted therapy. Ann N Y Acad Sci. 2012;1247(1):138–52.

Navarra S. V, Guzmán R.M., Gallacher A.E., Hall S., Levy R.A., Jimenez R.E., et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721–31.

Furie R., Petri M., Zamani O., Cervera R., Wallace D.J., Tegzová D., et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918–30.

van Vollenhoven R.F., Petri M.A., Cervera R., Roth D.A., Ji B.N., Kleoudis C.S., et al. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis. 2012;71(8):1343–9.

Sanz I., Lee F.E.-H. B cells as therapeutic targets in SLE. Nat Rev Rheumatol. 2010;6(6):326–37.

Wallace D.J., Stohl W., Furie R.A., Lisse J.R., McKay J.D., Merrill J.T., et al. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum. 2009;61(9):1168–78.

Steinman R.M. Dendritic cells: Understanding immunogenicity. Eur J Immunol. 2007;37(S1):S53–60.

Steinman R.M. Decisions About Dendritic Cells: Past, Present, and Future. Annu Rev Immunol. 2012;30(1):1–22.

Mowat A.M. Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol. 2003;3(4):331–41.

Denning T.L., Wang Y., Patel S.R., Williams I.R., Pulendran B. Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17–producing T cell responses. Nat Immunol. 2007;8(10):1086–94.

Platt A.M., Bain C.C., Bordon Y., Sester D.P., Mowat A.M. An Independent Subset of TLR Expressing CCR2-Dependent Macrophages Promotes Colonic Inflammation. J Immunol. 2010;184(12):6843–54.

Hutchinson J.A., Riquelme P., Sawitzki B., Tomiuk S., Miqueu P., Zuhayra M., et al. Cutting Edge: Immunological Consequences and Trafficking of Human Regulatory Macrophages Administered to Renal Transplant Recipients. J Immunol. 2011;187(5):2072–8.

Giannoukakis N., Phillips B., Finegold D., Harnaha J., Trucco M. Phase I (Safety) Study of Autologous Tolerogenic Dendritic Cells in Type 1 Diabetic Patients. Diabetes Care. 2011;34(9):2026–32.

Benham H., Nel H.J., Law S.C., Mehdi A.M., Street S., Ramnoruth N., et al. Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype–positive rheumatoid arthritis patients. Sci Transl Med. 2015;7(290):290ra87.

Jauregui-Amezaga A., Cabezón R., Ramírez-Morros A., España C., Rimola J., Bru C., et al. Intraperitoneal Administration of Autologous Tolerogenic Dendritic Cells for Refractory Crohn’s Disease: A Phase I Study. J Crohn’s Colitis. 2015;9(12):1071–8.

Bell G.M., Anderson A.E., Diboll J., Reece R., Eltherington O., Harry R.A., et al. Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis. Ann Rheum Dis. 2016;76(1):227–34.

Riquelme P., Haarer J., Kammler A., Walter L., Tomiuk S., Ahrens N., et al. TIGIT+ iTregs elicited by human regulatory macrophages control T cell immunity. Nat Commun. 2018;9(1):2858.

Labonte A.C., Kegerreis B., Geraci N.S., Bachali P., Madamanchi S., Robl R., et al. Identification of alterations in macrophage activation associated with disease activity in systemic lupus erythematosus. PLoS One. 2018;13(12):e0208132.

Gordon S. The macrophage: Past, present and future. Eur J Immunol. 2007;37(S1):S9–17.

Epelman S., Lavine K.J., Randolph G.J. Origin and Functions of Tissue Macrophages. Immunity. 2014;41(1):21–35.

Pelegrin P., Surprenant A. Dynamics of macrophage polarization reveal new mechanism to inhibit IL-1β release through pyrophosphates. EMBO J. 2009;28(14):2114–27.

Lindsey M.L., Saucerman J.J., DeLeon-Pennell K.Y. Knowledge gaps to understanding cardiac macrophage polarization following myocardial infarction. Biochim Biophys Acta - Mol Basis Dis. 2016;1862(12):2288–92.

Ben-Mordechai T., Palevski D., Glucksam-Galnoy Y., Elron-Gross I., Margalit R., Leor J. Targeting Macrophage Subsets for Infarct Repair. J Cardiovasc Pharmacol Ther. 2014;20(1):36–51.

Broichhausen C., Riquelme P., Geissler E.K., Hutchinson J.A. Regulatory macrophages as therapeutic targets and therapeutic agents in solid organ transplantation. Curr Opin Organ Transplant. 2012;17(4):332–42.

Riquelme P., Geissler E.K., Hutchinson J.A. Alternative approaches to myeloid suppressor cell therapy in transplantation: comparing regulatory macrophages to tolerogenic DCs and MDSCs. Transplant Res. 2012;1(17):1–14.

Conde P., Rodriguez M., van der Touw W., Jimenez A., Burns M., Miller J., et al. DC-SIGN+ Macrophages Control the Induction of Transplantation Tolerance. Immunity. 2015;42(6):1143–58.

Hutchinson J.A., Ahrens N., Geissler E.K. MITAP-compliant characterization of human regulatory macrophages. Transpl Int. 2017;30(8):765–75.

Robbins W.C., Holman H.R., Deicher H., Kunkel H.G. Complement Fixation with Cell Nuclei and DNA in Lupus Erythematosus. Exp Biol Med. 1957;96(3):575–9.

Miescher P., Strässle R. New Serological Methods for the Detection of the L.E. Factor. Vox Sang. 1957;2(4):283–7.

Vaglio A., Grayson P.C., Fenaroli P., Gianfreda D., Boccaletti V., Ghiggeri G.M., et al. Drug-induced lupus: Traditional and new concepts. Autoimmun Rev. 2018;17(9):912–8.

Fritzler M.J., Tan E.M. Antibodies to Histones in Drug-Induced and Idiopathic Lupus Erythematosus. J Clin Invest. 1978;62(3):560–7.


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