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Purpose: Anti-complement factor H (CFH) autoantibodies could be detected in lupus and its significance remained to be elucidated. Herein, we aimed to explore the roles of anti-CFH autoantibodies based on pristane-induced lupus mice.

Methods: Twenty-four female Balb/c mice were randomly divided into four groups, with one group injected with pristane (pristane group), one group with pristane and then human CFH (hCFH) (pristane-CFH group) 3 times, and the other two as vertical controls, PBS group and PBS-CFH group. Histopathological analysis was performed six months after pristane administration. Levels of hCFH, anti-CFH autoantibodies and anti-dsDNA antibody were detected. Murine IgG (mIgG) were purified and cross-reactivity, epitopes, subclasses and functional analysis were further evaluated in vitro.

Results: Immunization with hCFH and subsequent development of anti-CFH autoantibodies significantly attenuated nephritis of pristane-induced lupus, including lower levels of urinary protein and serum creatinine, decreased levels of serum anti-dsDNA antibody, greatly ameliorated renal histopathologic damage, decreased IgG, complements (C1q, C3) deposits and lower inflammatory factor (IL-6) expression in glomerulus. Furthermore, the purified mIgG (contained anti-CFH autoantibodies) could recognize both hCFH and murine CFH, and the epitopes were predominantly located in hCFH short consensus repeats (SCRs) 1-4, 7 and 11-14. The IgG subclasses were predominant IgG1. The autoantibodies could enhance the binding between hCFH and C3b, and increase factor I mediated-C3b lysis in vitro.

Conclusion: Our results suggested that anti-CFH autoantibodies could attenuate pristane-induced lupus nephritis by increasing bio-functions of CFH on regulating complement activation and controlling inflammation.

Titel:	Anti-complement factor H (CFH) autoantibodies could delay pristane-induced lupus nephritis.
Autor/in / Beteiligte Person:	Li, LL ; Luan, ZQ ; Tan, Y ; Wang, H ; Yu, XJ ; Qu, Z ; Yu, F ; Chen, M
Link:	View record at Springer (Volltext)
Zeitschrift:	Immunologic research, Jg. 71 (2023-12-01), Heft 6, S. 849-859
Veröffentlichung:	Totawa Nj : Humana Press ; <i>Original Publication</i>: Basel ; New York : S. Karger, [c1986-, 2023
Medientyp:	academicJournal
ISSN:	1559-0755 (electronic)
DOI:	10.1007/s12026-023-09396-y
Schlagwort:	Animals Female Humans Mice Autoantibodies Complement Factor H Epitopes Immunoglobulin G Immunologic Factors Mice, Inbred BALB C Lupus Nephritis chemically induced Lupus Nephritis immunology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Immunol Res] 2023 Dec; Vol. 71 (6), pp. 849-859. <i>Date of Electronic Publication: </i>2023 Jun 16. MeSH Terms: Lupus Nephritis* / chemically induced ; Lupus Nephritis* / immunology ; Animals ; Female ; Humans ; Mice ; Autoantibodies ; Complement Factor H ; Epitopes ; Immunoglobulin G ; Immunologic Factors ; Mice, Inbred BALB C References: J Clin Immunol. 2007 Sep;27(5):461-6. (PMID: 17587156) ; Protein Expr Purif. 2013 Oct;91(2):105-11. (PMID: 23906520) ; Pediatr Nephrol. 2019 Feb;34(2):269-281. (PMID: 30315407) ; Pharmacol Res. 2019 Jan;139:191-198. (PMID: 30471408) ; Lupus. 2018 Apr;27(4):545-555. (PMID: 28954590) ; J Am Soc Nephrol. 2011 Feb;22(2):285-95. (PMID: 21148254) ; Eur J Immunol. 1996 Oct;26(10):2383-7. (PMID: 8898949) ; Cochrane Database Syst Rev. 2009 Jan 21;(1):CD003595. (PMID: 19160220) ; Arthritis Res Ther. 2012 Aug 15;14(4):R185. (PMID: 22894814) ; J Am Soc Nephrol. 1993 Jul;4(1):58-61. (PMID: 8400070) ; J Clin Immunol. 2005 Nov;25(6):582-91. (PMID: 16380821) ; J Autoimmun. 2022 Oct;132:102871. (PMID: 35999111) ; Cytokine. 2006 Aug;35(3-4):148-53. (PMID: 17027280) ; Arthritis Care Res (Hoboken). 2018 Aug;70(8):1263-1268. (PMID: 29045037) ; Clin Chim Acta. 2020 Sep;508:1-8. (PMID: 32387092) ; Clin J Am Soc Nephrol. 2016 Jan 7;11(1):47-53. (PMID: 26700439) ; Immunol Rev. 2023 Jan;313(1):25-45. (PMID: 36382387) ; Arthritis Rheumatol. 2018 Jul;70(7):1089-1101. (PMID: 29481735) ; Autoimmun Rev. 2015 Jan;14(1):75-9. (PMID: 25449682) ; Kidney Dis (Basel). 2015 Sep;1(2):91-9. (PMID: 27536669) ; Nephrol Dial Transplant. 2022 Oct 19;37(11):2128-2137. (PMID: 34677610) ; Nephrol Dial Transplant. 2016 Aug;31(8):1235-42. (PMID: 26410885) ; Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):232-5. (PMID: 1729694) ; Am J Pathol. 1994 May;144(5):927-37. (PMID: 8178944) ; J Rheumatol. 2010 Jan;37(1):60-70. (PMID: 19955044) ; J Am Soc Nephrol. 2016 May;27(5):1334-42. (PMID: 26374608) ; PLoS One. 2016 Sep 15;11(9):e0160879. (PMID: 27631981) ; Front Immunol. 2022 Aug 23;13:931210. (PMID: 36091034) ; Immunology. 2006 Nov;119(3):296-305. (PMID: 17067309) ; J Am Soc Nephrol. 1998 Dec;9(12):2318-26. (PMID: 9848786) ; Am J Hematol. 2023 May;98 Suppl 4:S82-S89. (PMID: 36755352) ; FEBS Lett. 2016 Aug;590(15):2418-34. (PMID: 27393384) ; Springer Semin Immunopathol. 2006 Oct;28(2):175-84. (PMID: 16953439) ; J Immunol. 2015 Jun 1;194(11):5129-38. (PMID: 25917093) ; Am J Kidney Dis. 2005 Feb;45(2):415-21. (PMID: 15685522) ; Clin Rheumatol. 2021 Jul;40(7):2535-2545. (PMID: 33155159) ; Kidney Int. 2010 Aug;78(3):279-86. (PMID: 20445496) ; Front Immunol. 2018 May 09;9:958. (PMID: 29867943) ; J Exp Med. 1977 Jul 1;146(1):257-70. (PMID: 301546) ; Rheumatology (Oxford). 2012 Dec;51(12):2269-77. (PMID: 22956549) ; J Biol Chem. 2010 Jan 8;285(2):1053-65. (PMID: 19850925) ; Scand J Immunol. 1989 Dec;30(6):711-8. (PMID: 2532396) ; Immunobiology. 2014 Dec;219(12):980-9. (PMID: 25092568) ; Immunol Lett. 2018 May;197:1-8. (PMID: 29476755) ; Glycobiology. 2018 Oct 1;28(10):765-773. (PMID: 29982679) ; Proc Natl Acad Sci U S A. 1976 Sep;73(9):3268-72. (PMID: 1067618) Grant Information: 7212114 Natural Science Foundation of Beijing; YN2020ZD03 Peking University International Hospital Research Grant Contributed Indexing: Keywords: Anti-CFH autoantibodies; Complement activation; Complement factor H (CFH); Lupus nephritis; Pristane-induced lupus; Protective antibody Substance Nomenclature: 0 (Autoantibodies) ; 80295-65-4 (Complement Factor H) ; 0 (Epitopes) ; 0 (Immunoglobulin G) ; 0 (Immunologic Factors) ; 26HZV48DT1 (pristane) Entry Date(s): Date Created: 20230615 Date Completed: 20231218 Latest Revision: 20231218 Update Code: 20231219 PubMed Central ID: PMC10667379

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Anti-complement factor H (CFH) autoantibodies could delay pristane-induced lupus nephritis.