 |
 |
 |
 |
 |
 |
Sains Malaysiana 51(4)(2022): 1155-1165
http://doi.org/10.17576/jsm-2022-5104-17
Effect of Protein A-Immunoadsorption
Therapy on Serum Cytokines in AAV Patients
(Kesan Terapi A-Imunopenjerapan Protein ke atas Serum Sitokin pada Pesakit AAV)
XIEJIA LI1,2, ZHENG LI1,2,*, HONGMEI DENG1,
CUIFANG SUN1, HONG LIU1,2 & FANG YUAN1,2
1Department of Nephrology, the Second Xiangya Hospital, Central South University, Changsha,
Hunan, P.R. China
2Hunan Key Laboratory of Kidney Disease and Blood
Purification, Changsha, Hunan, P.R. China
Diserahkan:
18 Mei 2021/Diterima: 14 Oktober 2021
ABSTRACT
Protein
A-immunoadsorption (IA) is an extracorporeal apheresis technique used in
patients with autoimmune diseases which aims to remove pathogenic
autoantibodies. Apart from the adsorption of immunoglobulins (IgG), IA may
influence cellular and humoral immunity. The aim of this study was to observe
the effect of protein A-IA on cytokine networks in antineutrophil cytoplasmic
antibody (ANCA)-associated vasculitis (AAV) patients. A total of 12 newly
diagnosed AAV patients received IA therapy on days 1, 3, and 5. Serum levels of
inflammatory cytokines were measured before and after treatment including
members of the interleukin family, PDGF-BB, TNF-α and IFN-γ. IL-1β,
IL-9, IL-17A, PDGF-BB, IFN-γ, and TNF-α were elevated in AAV patients
compared to healthy individuals. There were no changes in the levels of any
cytokines after the first IA session but after 3 sessions, IL-9, PDGF-BB, and
TNF-α dramatically decreased. Moreover, reductions in IL-9 levels were
positively correlated with the changes of myeloperoxidase-ANCA
(MPO-ANCA). Our observations suggest that protein A-IA therapy does not
directly adsorb cytokines, but removes autoantibodies (MPO-ANCA) which
indirectly leads to changes in cytokine networks linked to cellular or humoral
immunity.
Keywords: Cytokines;
immunoadsorption; protein-A, ANCA; vasculitis
ABSTRAK
A-imunopenjerapan protein (IA) merupakan teknik ekstrakorporeum aferesis yang digunakan pada pesakit yang mempunyai penyakit autoimun bertujuan untuk menyingkirkan autoantibodi patogen. Selain daripada penjerapan immunoglobulin (IgG), IA boleh mempengaruhi imuniti sel dan humoral. Tujuan kajian ini adalah untuk melihat kesan protein A-IA ke atas rangkaian sitokin pada pesakit vasculitis (AAV) yang berkait dengan antibodi sitoplasmik antineutrofil (ANCA). Seramai 12 pesakit AAV yang baru didiagnos telah menerima terapi IA pada hari 1, 3 dan 5. Tahap serum daripada keradangan sitokin telah diukur sebelum dan selepas rawatan termasuk anggota daripada keluarga interleukin, PDGF-BB, TNF- α dan IFN-γ. IL-1β,
IL-9, IL-17A, PDGF-BB, IFN-γ dan TNF-α menaik pada pesakit AAV berbanding dengan individu yang sihat. Tiada perubahan pada tahap dalam mana-mana sitokin selepas sesi pertama IA tetapi selepas sesi ketiga, IL-9, PDGF-BB dan
TNF-α menurun dengan mendadak. Selain itu, penurunan dalam paras IL-9 berkorelasi secara positif dengan perubahan mieloperoksidase-ANCA (MPO-ANCA). Berdasarkan pemerhatian kami, terapi protein A-IA tidak menjerap sitokin secara langsung, tetapi mengeluarkan autoantibodi (MPO-ANCA) yang secara tidak langsung mengakibatkan perubahan kepada rangkaian sitokin yang berpaut kepada imuniti sel atau humoral.
Kata kunci: ANCA; imunopenjerapan; protein-A; sitokin;
vasculitis
RUJUKAN
Aljuhani, M., Makati, D., Hoff, A.,
Thompson, J., Pellegrino, B., Shawwa, K., Schmidt, R.
& Kannabhiran, D. 2021. Antibody subtypes and
titers predict clinical outcomes in ANCA-associated vasculitis. Rheumatology International 41(5):
965-972.
Baggi,
F., Ubiali, F., Nava, S., Nessi,
V., Andreetta, F., Rigamonti,
A., Maggi, L., Mantegazza, R. & Antozzi, C. 2008. Effect of IgG immunoadsorption on serum
cytokines in MG and LEMS patients. Journal
of Neuroimmunology 201: 104-110.
Braun,
N. & Risler, T. 1999. Immunoadsorption as a tool
for the immunomodulation of the humoral and cellular immune system in
autoimmune disease. Therapeutic Apheresis 3(3): 240-245.
Bossuyt, X., Tervaert,
J.W.C., Arimura, Y., Blockmans,
D., Flores-Suárez, L.F., Guillevin, L., Hellmich, B.,
Jayne, D., Jennette, J.C., Kallenberg, C.G. & Moiseev, S. 2017. Revised 2017 International Consensus on
testing of ANCAs in granulomatosis with polyangiitis and microscopic
polyangiitis. Nature Reviews Rheumatology 13(11): 683-692.
Bulut,
D., Creutzenberg, G. & Mügge,
A. 2013. The number of regulatory T cells correlates with hemodynamic
improvement in patients with inflammatory dilated cardiomyopathy after
immunoadsorption therapy. Scandinavian
Journal of Immunology 77(1): 54-61.
Bulut, D., Scheeler, M., Wichmann, T., Börgel, J., Miebach, T. & Mügge, A. 2010. Effect of protein A immunoadsorption on T
cell activation in patients with inflammatory dilated cardiomyopathy. Clinical Research in Cardiology 99(10):
633-638.
Casian,
A. & Jayne, D. 2011. Plasma exchange in the treatment of Wegener's
granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and renal
limited vasculitis. Current Opinion in
Rheumatology 23(1): 12-17.
Cornec, D., Cornec-Le
Gall, E., Fervenza, F.C. & Specks, U. 2016.
ANCA-associated vasculitis - Clinical utility of using ANCA specificity to
classify patients. Nature Reviews
Rheumatology 12(10): 570-579.
Flossmann, O., Berden,
A., de Groot, K., Hagen, C., Harper, L., Heijl, C., Höglund, P., Jayne, D., Luqmani,
R., Mahr, A. & Mukhtyar,
C. 2011. Long-term patient survival in ANCA-associated vasculitis. Annals of the Rheumatic Diseases 70(3):
488-494.
Gaskin,
G. & Pusey, C.D. 2001. Plasmapheresis in antineutrophil cytoplasmic
antibodies‐associated systemic vasculitis. Therapeutic Apheresis 5(3): 176-181.
Gioffredi, A., Maritati,
F., Oliva, E. & Buzio, C. 2014. Eosinophilic
granulomatosis with polyangiitis: An overview. Frontiers in Immunology 5: 549.
Goto, H., Matsuo, H., Nakane, S., Izumoto, H., Fukudome, T., Kambara,
C. & Shibuya, N. 2001. Plasmapheresis affects T helper type‐1/T
helper type‐2 balance of circulating peripheral lymphocytes. Therapeutic Apheresis 5(6): 494-496.
Hehmke, B., Salzsieder,
E., Matic, G.B., Winkler, R.E., Tiess, M. & Ramlow, W. 2000. Immunoadsorption of immunoglobulins alters
intracytoplasmic type 1 and type 2 T cell cytokine production in patients with
refractory autoimmune diseases. Therapeutic
Apheresis 4(4): 296-302.
Hogan, S.L., Falk, R.J., Chin, H.,
Cai, J., Jennette, C.E., Jennette, J.C. & Nachman, P.H. 2005. Predictors of
relapse and treatment resistance in antineutrophil cytoplasmic
antibody-associated small-vessel vasculitis. Annals of Internal Medicine 143(9): 621-631.
Inganäs, M. 1981. Comparison of mechanisms
of interaction between protein A from Staphylococcus
aureus and human monoclonal IgG, IgA and IgM in relation to the classical Fcγ and the alternative F(ab')2γ protein A
interactions. Scandinavian Journal of
Immunology 13(4): 343-352.
Ishizaki, J., Takemori, A., Suemori, K., Matsumoto, T., Akita, Y., Sada,
K.E., Yuzawa, Y., Amano, K., Takasaki, Y., Harigai,
M. & Arimura, Y. 2017. Targeted proteomics
reveals promising biomarkers of disease activity and organ involvement in
antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Research & Therapy 19(1): 1-17.
Jennette, J.C., Falk, R.J., Bacon,
P.A., Basu, N., Cid, M.C., Ferrario,
F., Flores-Suarez, L.F., Gross, W.L., Guillevin, L., Hagen, E.C. & Hoffman,
G.S. 2013. Arthritis Rheum. In 2012
Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. CHCC. pp. 1-11.
Kemna, M.J., Damoiseaux, J., Austen,
J., Winkens, B., Peters, J., van Paassen,
P. & Tervaert, J.W.C. 2015. ANCA as a predictor
of relapse: Useful in patients with renal involvement but not in patients with
nonrenal disease. Journal of the American
Society of Nephrology 26(3): 537-542.
Kronbichler, A., Leierer,
J., Gauckler, P. & Shin, J.I. 2020a.
Comorbidities in ANCA-associated vasculitis. In Rheumatology. Oxford: Oxford University Press. pp. iii79-iii83.
Kronbichler, A., Lee, K.H., Denicolò,
S., Choi, D., Lee, H., Ahn, D., Kim, K.H., Lee, J.H.,
Kim, H., Hwang, M. & Jung, S.W. 2020b. Immunopathogenesis of
ANCA-associated vasculitis. International
Journal of Molecular Sciences 21(19): 7319.
Kronbichler, A., Leierer,
J., Shin, J.I., Merkel, P.A., Spiera, R., Seo, P., Langford, C.A., Hoffman, G.S., Kallenberg,
C.G., St Clair, E.W. & Brunetta, P. 2019.
Association of pulmonary hemorrhage, positive proteinase 3, and urinary red
blood cell casts with venous thromboembolism in antineutrophil cytoplasmic
antibody–associated vasculitis. Arthritis
& Rheumatology 71(11): 1888-1893.
Kronbichler, A., Jayne, D.R. & Mayer, G.
2015. Frequency, risk factors and prophylaxis of infection in
ANCA‐associated vasculitis. European
Journal of Clinical Investigation 45(3): 346-368.
Lai, Q.Y., Ma, T.T., Li, Z.Y., Chang, D.Y., Zhao, M.H. & Chen,
M. 2014. Predictors for mortality in patients with antineutrophil cytoplasmic
autoantibody associated vasculitis: A study of 398 Chinese patients. J. Rheumatol. 41(9): 1849-1855.
Le Guenno,
G., Mahr, A., Pagnoux, C., Dhote, R., Guillevin, L. & French Vasculitis Study
Group. 2011. Incidence and predictors of urotoxic adverse events in cyclophosphamide‐treated
patients with systemic necrotizing vasculitides. Arthritis & Rheumatism 63(5):
1435-1445.
Li, Z.Y., Ma, T.T., Chen, M. &
Zhao, M.H. 2015. The prevalence and management of anti-neutrophil cytoplasmic
antibody-associated vasculitis in China. Kidney
Diseases 1(4): 216-223.
Lilliebladh,
S., Johansson, Å., Pettersson, Å., Ohlsson, S. & Hellmark, T. 2018. Phenotypic characterization of
circulating CD4+ T cells in ANCA-associated vasculitis. Journal of Immunology Research 2018: 6984563.
Lyons, P.A., Rayner, T.F., Trivedi,
S., Holle, J.U., Watts, R.A., Jayne, D.R., Baslund, B., Brenchley, P., Bruchfeld, A., Chaudhry, A.N. & Cohen Tervaert, J.W. 2012. Genetically distinct subsets within
ANCA-associated vasculitis. New England
Journal of Medicine 367(3): 214-223.
Mahr, A., Heijl, C., Le Guenno, G. & Faurschou, M.
2013. ANCA-associated vasculitis and malignancy: Current evidence for cause and
consequence relationships. Best Practice
& Research Clinical Rheumatology 27(1): 45-56.
Maillard, N., Absi,
L., Claisse, G., Masson, I., Alamartine,
E. & Mariat, C. 2015. Protein A-based
immunoadsorption is more efficient than conventional plasma exchange to remove
circulating anti-HLA antibodies. Blood
Purification 40(2): 167-172.
Martinez
Valenzuela, L., Bordignon Draibe,
J., Fulladosa Oliveras, X., Bestard Matamoros, O., Cruzado Garrit,
J.M. & Torras Ambrós,
J. 2019. T-lymphocyte in ANCA-associated vasculitis: What do we know? A
pathophysiological and therapeutic approach. Clinical Kidney Journal 12(4): 503-511.
Monach, P.A., Warner, R.L., Tomasson, G., Specks, U., Stone, J.H., Ding, L., Fervenza, F.C., Fessler, B.J., Hoffman, G.S., Iklé, D. & Kallenberg, C.G.
2013. Serum proteins reflecting inflammation, injury and repair as biomarkers
of disease activity in ANCA-associated vasculitis. Annals of the Rheumatic Disease 72(8): 1342-1350.
Palmer, A., Cairns, T., Dische, F., Gluck, G., Gjorstrup,
P., Parsons, V., Welsh, K. & Taube, D. 1991. Treatment of rapidly
progressive glomerulonephritis by extracorporeal immunoadsorption, prednisolone
and cyclophosphamide. Nephrology Dialysis
Transplantation 6(8): 536-542.
Philipponnet, C., Garrouste,
C., Le Guenno, G., Cartery,
C., Guillevin, L., Boffa, J.J. & Heng, A.E. 2017.
Antineutrophilic cytoplasmic antibody-associated vasculitis and malignant
hemopathies, a retrospective study of 16 cases. Joint Bone Spine 84(1): 51-57.
Rahmattulla, C., Mooyaart,
A.L., van Hooven, D., Schoones,
J.W., Bruijn, J.A., Dekkers,
O.M., Bajema, I.M. & European Vasculitis Genetics
Consortium. 2016. Genetic variants in ANCA-associated vasculitis: A
meta-analysis. Annals of the Rheumatic
Diseases 75(9): 1687-1692.
Rowaiye, O.O., Kusztal,
M. & Klinger, M. 2015. The kidneys and ANCA-associated vasculitis: From
pathogenesis to diagnosis. Clinical
Kidney Journal 8(3): 343-350.
Schneidewind‐Müller, J.M., Winkler, R.E., Tiess, M., Müller, W. & Ramlow,
W. 2002. Changes in lymphocytic cluster distribution during extracorporeal
immunoadsorption. Artificial Organs 26(2): 140-144.
Stegmayr, B., Almroth,
G., Berlin, G., Fehrman, I., Kurkus,
J., Norda, R., Olander, R., Sterner, G., Thysell, H., Wikström, B. & Wiren, J.E. 1999. Plasma exchange or immunoadsorption in
patients with rapidly progressive crescentic glomerulonephritis a Swedish
multi-center study. The International
Journal of Artificial Organs 22(2): 81-87.
Szczeklik, W., Jakieła,
B., Wawrzycka‐Adamczyk, K., Sanak,
M., Hubalewska‐Mazgaj, M., Padjas,
A., Surmiak, M., Szczeklik,
K., Sznajd, J. & Musiał,
J. 2017. Skewing toward Treg and Th2 responses is a
characteristic feature of sustained remission in ANCA‐positive
granulomatosis with polyangiitis. European
Journal of Immunology 47(4): 724-733.
Tanna, A., Guarino, L., Tam, F.W., Rodriquez-Cubillo,
B., Levy, J.B., Cairns, T.D., Griffith, M., Tarzi,
R.M., Caplin, B., Salama, A.D. & Cook, T. 2015. Long-term outcome of
anti-neutrophil cytoplasm antibody-associated glomerulonephritis: Evaluation of
the international histological classification and other prognostic factors. Nephrology Dialysis Transplantation 30(7): 1185-1192.
Tomasson,
G., Grayson, P.C., Mahr, A.D., LaValley,
M. & Merkel, P.A. 2012. Value of ANCA measurements during remission to
predict a relapse of ANCA-associated vasculitis - A meta-analysis. Rheumatology 51(1): 100-109.
Unizony,
S., Villarreal, M., Miloslavsky, E.M., Lu, N.,
Merkel, P.A., Spiera, R., Seo,
P., Langford, C.A., Hoffman, G.S., Kallenberg, C.M.
& Clair, E.W.S. 2016. Clinical outcomes of treatment of anti-neutrophil
cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type. Annals of the Rheumatic Diseases 75(6):
1166-1169.
Wallace, Z.S., Fu, X., Harkness, T.,
Stone, J.H., Zhang, Y. & Choi, H. 2020. All-cause and cause-specific
mortality in ANCA-associated vasculitis: Overall and according to ANCA type. Rheumatology 59(9): 2308-2315.
Watanabe, H., Sada,
K.E., Matsumoto, Y., Harigai, M., Amano, K., Dobashi, H., Fujimoto, S., Usui, J., Yamagata, K., Atsumi, T. & Banno, S. 2018.
Association between reappearance of myeloperoxidase - antineutrophil
cytoplasmic antibody and relapse in antineutrophil cytoplasmic antibody -
associated vasculitis: Subgroup analysis of nationwide prospective cohort
studies. Arthritis & Rheumatology 70(10): 1626-1633.
Watts,
R.A., Mahr, A., Mohammad, A.J., Gatenby,
P., Basu, N. & Flores-Suárez, L.F. 2015.
Classification, epidemiology and clinical subgrouping of antineutrophil
cytoplasmic antibody (ANCA) - associated vasculitis. Nephrology Dialysis Transplantation 30: i14-i22.
Xiao, H., Hu, P., Falk, R.J. &
Jennette, J.C. 2015. Overview of the pathogenesis of ANCA-associated
vasculitis. Kidney Diseases 1(4):
205-215.
Yokoyama, H., Wada, T. & Furuichi, K. 2003. Immunomodulation effects and clinical
evidence of apheresis in renal diseases. Therapeutic
Apheresis and Dialysis 7(6): 513-519.
*Pengarang untuk surat-menyurat; email: lizheng2064@csu.edu.cn
|
|||
|
