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23-9-第九节 抗中性粒细胞胞浆抗体
抗中性粒细胞胞浆抗体(antineutrophil cytoplasmic antibody, ANCA)是一种以中性粒细胞和单核细胞胞浆成分为靶抗原的自身抗体。1982年,Davies等在8例节段性坏死性肾小球肾炎患者血清中首次发现了ANCA。现已发现,ANCA自身抗体谱存在十余种特异性抗体,ANCA对系统性血管炎、炎性肠病和自身免疫性肝病等疾病的诊断与鉴别诊断具有重要意义。ANCA已成为自身免疫病重要的临床常规检测项目(详见第22章)。ANCA是自身免疫性肝病标准诊断谱的最新成员,主要见于自身免疫性肝病中的AIH-Ⅰ型及 PSC患者中,而PBC患者则少见。自身免疫性肝病中出现的ANCA,其免疫荧光染色型为核周型 ANCA(perinuclear ANCA, pANCA)或非典型性AN-CA(atypical ANCA, aANCA或xANCA)。其特异性靶抗原尚未完全清楚,可能是肌动蛋白(actin)或位于核板层(lamina)的某些粒细胞特异性抗原成分,而不同于原发性系统性血管炎患者中ANCA所常对应的特异性靶抗原,如蛋白酶3 ( proteinase 3, PR3)和髓过氧化物酶(myeloperoxidase, MPO)等。* V2 C7 o$ p$ a8 _2 a& `
' J' h$ s/ e; i" P 一、检测方法
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2 J4 b- g2 e4 q4 j 因尚未完全清楚自身免疫性肝病中出现的ANCA所对应的特异性靶抗原,以肝胆损伤等症状为主的自身免疫性肝病患者,常规检测ANCA可只选用间接免疫荧光法,检测结果ANCA阳性免疫荧光染色型多为pANCA或aANCA。9 l: ]0 I( ]3 J) s* L) y: P' z( D
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二、临床意义
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pANCA主要见于自身免疫性肝病中的AIH-Ⅰ型及 PSC患者中,阳性率分别为 65%~92%,29%~88%,而AIH- II型、PBC及其他非自身免疫性肝病患者中则少见。ANCA检测有助于自身免疫性肝病患者的诊断、分型及鉴别诊断,并可用于慢性隐源性肝病的分类。
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pANCA与AIH-Ⅰ型的疾病活动度(转氨酶和γ-球蛋白水平)相关,ANCA阳性患者的病情常较重。pANCA阳性的PSC患者,合并溃疡性结肠炎(ulcerative colitis, UC)的可能性较大,亦与胆管树受累广度相关,病情往往较重。 ' Z2 j& |6 ?* _' E$ o# e3 Y' ?
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9 U' A. T2 D2 \& p0 j 参考文献4 ~3 m- n, Z7 @8 ?, m0 Q- G/ K! k/ _2 a! L5 v
$ M# p& p& u5 V0 w+ [" R* D9 d
董怡.自身免疫性肝炎是否一独立疾病 .中华风湿病学杂志,1998.2(2):63一64
* r4 d- M# ?& a) o7 Y" |) v! o1 E2 [
滑立伟,张煊 .临床病例讨论 第 12例一呕血、口干、眼干、粒细胞缺乏 .中华风湿病学杂志,2001.5(4):2“一267 ) i) c8 R/ D, H
% H- _8 G% v( ~5 \ 刘厚饪.重视对自身免疫性肝炎的研究 .肝脏,2000.5(2):65
, h; X, a$ i+ D
3 g0 ~, b: g: H! i 伍沪生,宋慧,黄彦弘,等 .原发性干燥综合征的肝脏损害.中华风湿病学杂志,2001.5(1):29一31 $ {' A$ b. C# n2 c a! B B
f9 O% |2 D: L1 F1 t' @ 张福奎,贾继东,王宝恩,等 .45例原发性胆汁性肝硬化的临床特征.中华内科杂志,2002.41(3):163一167 , b# d5 n8 N; i8 L
; d+ ^* g! Q, X) s4 z8 A7 n
张煊,林进,唐福林,等 .原发性胆汁性肝硬化的临床及病理分析 .中华风湿病学杂志,2001.5(2):98一101
3 D. t: _# O" q
6 L3 T2 ?' q( Y' k3 u) V Abuaf N,]ohanet C,chretien P, et al. Characterisation of theLiver Cytosol antigen Type 1 reacting with autoantibodies inchronic active hepatitis. HEpatology,1992. 16:892一898
3 o# ?2 q) O& `2 O5 l, P" ]% B- s3 e% D' E
Albert J. , Czaja, Henry A. Homburger. Autoantibodies in liv-er disease. Gastroenterology, 2001.120:239一249
! o/ P) }' W5 C; r$ h: N; c! U' \4 n% ?" Q% ?4 M8 m& j. \" b6 U* l
Andrae LE,Chan EK,Raska I, et al. Human autoantibody toa novel protein of the nuclear coild body :Immunological Charac-terization and cDNA cloing of p80- coilin. J Exp Med,1991,173:1407一1419 ; E% @! ~- ]- |5 |2 Z& O
3 j: n0 i/ Y6 v0 \2 y v* ] Bandin 0,Courvalin JC,Poupon R, et al. Specificity and sen-sitivity of gp210 autoantibodies detected using an enzyme-linkedimmunosorbent assay and a synthetic polypeptide in the diagnosisof primary biliary cirrhosis. HEpatology,1996.23:1020一1024
6 K* \2 ?+ t* f* C
/ |- [% i, \; k0 J- M/ o* C4 @ Bansi D, Chapman R, Fleming K. Antineutrolphil cytoplas-mic antibodies in chronic liver disease: prevalence, titre, specifici-ty and IgG subclass. J HEpato1,1996. 24:581一586 . e' N F6 Z, H: e( x8 U ]5 a
8 A/ f& [- s. L Berg PA, Klein R二Antimitochondrial antibodies in primarybiliary cirrhosis and other disorders: definition and clinical rele-vance. Dig Dis,1992.10:248一264 ! m9 {! k" o, t0 F( L
; ^0 N/ v, T0 R5 o7 v+ F Bluthner M,Schafer C and Schneider, et al. Identification ofmajor epitopes on the Sp100 nuclear PBC autoantigen by thegene-fragment phage-display technology. Autoimmunity, 1999.29:32一42
- j. q3 m7 R0 `$ z* e* D6 @4 s. e, z" m1 K2 S; q
Bylund DMchutchison J. Autoimmune liver diseaes. Clin LabMED, 1997, 17: 483一497. - ~# @# t$ e0 Q. s
7 G. F6 F( U5 `
Cancado ELR, Vilas-Boas LS,Abrantes-lemos CP, et al. Heat serum inactivation as a mandatoryprocedure for antiactin antibody detection in cell culture. HEpa-tology,1996.23:1098一1104
* i3 a$ m# T. L2 R, C$ T+ b+ j( L
2 E! Z6 ~& q9 Y8 |/ E9 K# i Chen M, Shirai M, Czaja AI, et al. Characterization of anti-histone antibodies in patients with type 1 autoimmune hepatitis. JGastroenterol HEpatol 1998.13:483一489 0 V( {, `- L5 i% j2 {( E% T( R- J* k
+ n, X- s5 i$ s; V
Courvalin JC, Worman I{I. Nuclear envelop protein autoanti-bodies in primary biliary cirrhosis. Semin Liver Dis 1997.17:79一90
& {4 F( S8 T" q+ J ^
6 ~4 z2 J2 @5 M! p5 O) b! N Czaja AJ, Cassani F, Cataleta M, et al. Antinuclear antibodiesand patterns of nuclear immunofluorescence in type 1 autoimmunehepatitis. Dig Dis Sci 1997.42:1688一1696
" G( Q* v5 e1 f: j* z
4 ~- y: b f! a/ F Czaja AJ, Manns MP, Homburger HA et al. Frequency andsignificance of antibodies to liver/ kidney microsome antibodiestype 1 in adults with chronic active hepatitis. Gastroenterology,1992.103:1290一1295 ; T% ^7 c$ D+ C. c7 @2 k: z h, `# ]
! ~1 O" [% Q$ X7 S Czaja幻,Manns MP. The validity and importance of sub-types of autoimmune hepatitis: a point of view. Am J Gastroen-terol 1995. 90:1206一1211
9 x- j n- ]8 e. W1 G6 Q& I9 U3 b7 L* o% K9 m
Czaj a川,Ming C,Shirai M, et al. Frequency and significanceof antibodies to histones in autoimmune hepatitis. J HEpatol1995.23:32一38
4 x3 m( J6 C1 z
8 w& @' w1 q! b1 U W' a6 A- I. d Czaja Aj, Morshed SA, Parveen S, et al. Antibodies to singlestranded and double-stranded DNA in antinuclear antibody posi-tive type 1 autoimmune hepatitis. HEpatologe, 1997. 26: 567一573 . J e) K* c1 A: F+ ]2 x
4 Y u7 j! m8 O1 y
Dighiero G, Lymberi P, Monot C et al. Sera with high levelsof anti-smooth muscle and anti-mitochondrial antibodies frequentlybind to cytoskeletal proteins. Clin Exp Immunol 1990.82:52一56 - S: I( G5 l" Q Q; D. F
$ l O, T2 ?, Z; x; @6 p Duclos-Vallee JC, Hajoui O, Yamamoto AM, et al. Comfor-mational epitopes on CYP2D6 are recognized by liver/ kidney mi-crosome antibodies. Gastroenterology,1995.108:470一476 ; I& i1 ~0 R( l5 b9 e5 K
7 I/ l) x9 M0 Y+ t7 u! f Durazzo M, Philip T, Van Pelt FNAM, et al. Heterogeneityof Liver-Kidney Microsomal autoantibodies in chronic hepatitis Cand D virus infection. Gastroenterology, 1995.108:455一462
# N9 L$ Q/ o$ T% @3 N. L' O
/ b/ J k6 y8 A Fusconi M,Cassani F, Zauli D, et al. Anti-actin antibodies: anew test for an old problem. J Immunol Methods, 1990. 130:1一8 5 R( p4 ^" t; B6 Z1 n+ D3 m6 J' ?
2 H! `; E3 Y" K Hill C,Roberts-Thompson P,Pollard A,et al. Clinical associ-ations of anti-lamin antibodies. Aust N J Med 1996.26:162一166
* c1 d5 m% W; s
! G7 k5 S2 ^& c s- V9 ~ Ingrid Wies,Silvia Brunner,Juergen Henninger,et al. Identi-fication of target antigen for SLA/LP autoantibodies in autoim-mune hepatitis. Lancet, 2000.355:1510一1515 + X ]5 n5 _) l' G! F+ O( i0 q# w' M
; h2 L9 B7 m4 v1 |5 `5 \# r
Itoh S, Ichida T, Yoshida T, et al. Autoantibodies against a210 Kda glycoprotein of the nuclear pore complex as a prognosticmarker in patients with primary biliary cirrhosis. J Gastroen-terology HEpatol 1998. 13:257一265
- y5 Z) N- k# a; O2 D0 }3 M: G8 A3 q6 A& ^+ y) i0 o7 ^7 _3 L
Klein R,Berg PA. Glutathione S-transferase as a major au-toantigen in anti-SLA-positive autoimmune hepatitis(letter).Gas-troenterology,1999.116:1015一1016
; I# Q; ?! V; P8 Y3 V! ^% [4 e( u7 ]9 ]! g0 o* ?1 z0 g+ Q5 [4 q
Konstantinov K,von Mikeez A,Buchwald D, et al. Autoanti-bodies to nuclear envelop antigens in chronic fatigue syndrome. JClin Invest 1996.98:1888一1896 ( ?' Z4 S+ t+ r. B% C
0 I' s6 G2 R2 |. `4 S! z! e LaBrecque DR, Phillips MJP, lppolito LA, et al. Antineu-trolphil cytoplasmic antibody and chronic liver disease(abstr ).HEpatology, 1999.30:428A
9 Q) c8 d0 r$ t& z: D9 E5 ~: i5 d
Lenzi M, Manotti P, Muratori L, et al. Liver Cytosolic 1antigen- antibody system in type 2 autoimmune hepatitis and hep-atitis C virus infection. Gut, 1995. 36:749一754 ! M8 Z8 ~. s9 |2 B
9 ]' y5 R' _3 o/ F6 P! X; t7 T4 ?5 [
Lin F, Noyer CM, Ye Q, et al. Autoantibodies from patientswith primary biliary cirrhosis recognize a region within the nucleo-plasmic domain of inner nuclear membrane protein LBR. HEpa-tology,1996. 23:57一61 ( S8 K! s) C5 {+ D
& B+ \9 x1 z: k) d
Ma Y, Peakman M, Lobo-Yeo A, et al. Differences in im-mune recognition of cytochrome P450D6 by liver kindney micro-somal(LKM) antibody in autoimmune hepatitis and chronic hep-atitis C virus infection. Clin Exp Immuno1,1994. 97:94一99 % M2 P2 n$ m" U1 }$ H/ {
0 f- w* R% S" x- F7 R& d McFarlane IG. The relationship between autoimmune mark-ers and different clinical syndromes in autoimmune hepatitis. Gut,1998.42:599一602 $ R' s& o. ]) X" |$ }0 h
: I( M) N v* Z: m
McHugh NJ,James IE, Kairburn K, et al. Autoantibodies tomitochondria) and centromere antigens in primary biliary cirrhosisand systeemic sclerosis. Clin Exp Immuno1,1990. 81:244一249 7 G& e" }7 g* G7 E& I
$ |" r' F0 r. }# u- n Michael P. Manna and Christian P. Strassburg. Autoimmunehepatitis: clinical challenges. Gastroenterology,2001.120:1502-1517 4 _9 e, j9 E8 Z R W
' N3 W7 C. s# l$ M8 k
Miyakawa H, Kikuchi K, Jong-Hon K, et al. High sensitivi-ty of a novel ELISA for anti-M2 in primary biliary cirrhosis. JGastroenterol, 2001.36:33一38
/ w ~( H6 K+ s8 z7 |1 h- p8 G. r0 s( C
Muratori L,Cataleta P,Muratori P, et al. Liver/ kidney mi-crosomal antibody type land liver cytosol antibody type 1 in type2 autoimmune hepatitis. Gut, 1999. 42:721一726
+ ?7 G- C- R, V! P9 u# t4 U/ }9 ]6 L
; ~' P5 O. O# x: W2 ]/ s Onouchi H, Muro Y, Tomita Y. Clinical features and tgGsubclass distribution of anti-p80 coilin antibodies. J Autoimmun,1999.13:225一232 8 |# d6 `3 v! T R3 l0 G0 b
$ l" G9 e+ J+ H8 r8 ^2 U. { Orth T, Gerken, Zum M, et al. Actin is a target of antineu-trolphil cytoplasmic antibodies (ANCA) in autoimmune hepatitistype 1. J HEpatolalogy, 1996.24:581一586 + S! J x$ w( A3 v% `$ a
' @- A# P1 m) `( h% X1 _
Senecal JL, Rauch J , Grodzicky T, et al. Strong association ofautoantibodies to human nuclearlant antibodies in systemic lupuslamin B1 with lupus anticoagu-erythematosus. Arthritis Rheum1999.42:1347一53
1 j# q! P6 C( x/ ^, R! z9 l0 A0 A9 M% ]7 z" z3 H+ X; r. j. @
Sternsdorf T, Guldner HH, Szostecki C, et al. Two nucleardotassociated proteins, PMLand sp100, are often co-autoim-munnogenic in patients with primary biliary cirrhosis. Scand J Im-muno1,1995. 42:257一268
* L% D$ I% c f, a4 E1 \) x9 [8 ^8 H7 M' F! T
Szostecki C,Guldner HH and Will H. Autoantibodies against"nuclear dots" in primary biliary cirrhosis. Seminars in Liver Dis-ease, 1997.17:71一78
4 i$ R; `: A9 A2 P9 f5 ?7 e# N" {: E1 j! l; M
Targan RS, landers C, Vidrich A, et al. High-titer antineu-trolphil cytoplasmic antibodies in type 1 autoimmune hepatitis.Gastroenterology,1995.108:1159一1166
5 F9 V6 E. K! d/ h7 D3 Q+ Z; ~' e* _" R
reichel U, Gerken G, Rossol S, et al. Autoantibodies a-gainst the human asialoglycoprotein receptor: effects of therapy inautoimmune and virus-induced chronic active hepatitis. J HEpatol,1993.19:55一63 : ^1 T$ h8 N" p( o/ M6 y; Q: f( k% o
( l8 W9 M& M2 B' m; g- V" q+ H
Treichel U,Porallat,Hess G, et al. Autoantibodies to humanasialoglycoprotein receptor in autoimmune-type chronic hepatitis.HEpatology,1990.11:606一612
. v0 ]$ v' q U+ F4 q
- q0 G/ P, V: N1 s# a Wesierska-Gadek J, Grimm R, Hitchman E, et al. Membersof the Glutathione S-transferase gene family are antigens in au-toimmune hepatitis. Gastroenterology,1998. 114:329一335 www.ikang.org
% r1 @: [1 Z6 B, n# x4 [! r9 V# }& S& k* n; e4 d. }
WesierskaGadek J, Hohenuer H, Hitchman E, et al. Au-toantibodies from patients with primary biliary cirrhosis preferen-tially react with the amino-terminal domain of nuclear pore com-plex glycoprotein gp210. J Exp Med 1995.182(4):1159一1162
! T- D% I* m) L( _- i L9 }0 t- _& P* \! L4 A
Wesierska-Gadek J,Hohenuer H, Hitchman E, et al. Autoan-tibodies against nucleoporin p62 consitute a novel marker of pri-mary biliary cirrhosis. Gastroenterology 1996. 110:840一847 q1 a' z0 z4 ^$ y- W5 M7 R
6 Q2 @ m e# U: n
Zauli D, Ghetti S, Grassi A, et al. Anti- neutrolphil cytoplas-mic antibodies in type 1 and type 2 autoimmune hepatitis. HEpa-tology, 1997.25:1105一1107 |
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