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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。7 q" O) L1 ^: x* u2 {9 f; Z0 g
- M2 e$ N- _$ z: a' v 一、检测方法 ! |1 q2 r) _) H9 h8 _3 u! u
4 Q& c- k( N! O0 T5 {/ M+ e5 z* [ 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。
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& E/ l9 d8 I7 y 二、临床意义 ' }6 d# }% _6 r# P# a; w
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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。 # S5 O, a2 Q( U
! w& `1 ]6 [& `) o, N+ BpANCA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。
6 L2 m3 o1 J( ` (李永哲 )
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6 R' ?0 C+ c; `& r 参考文献
! p! r, ?9 t$ U/ {; i, |6 v/ p* ]* p* e7 ?. Z' c
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
3 h7 A# t0 H/ d7 q' @& k9 q
* ?# r/ g5 H9 a6 p9 ?- @; t 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
, }. d5 I2 W8 d1 K
# z4 B* K2 P J 刘厚饪.重视对自身免疫性肝炎的研究 .肝脏,2000.5(2):65 . F( h# B8 K6 I. U- A' T
. ^$ C2 o4 @! ?! V( @ 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
+ P5 _4 z1 J$ ^" R6 L: P# r- P; G7 i1 h
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
2 G; ~5 E! I. M4 V2 X
7 V$ l. B3 e/ m9 {0 A) w6 d& t' t 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 @$ y5 L8 B3 B3 c+ x. p9 R" y
0 p% a: Z- v6 S. D; ^ P 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
$ ?. s% B- U% X7 p) T& A m% z) v4 L" N7 Z
Albert J. , Czaja, Henry A. Homburger. Autoantibodies in liv-er disease. Gastroenterology, 2001.120:239一249
3 W& x7 m5 a0 j5 P& x2 n+ Y: I1 i9 k- m, C
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 0 R8 z2 E' z+ k0 F
7 t. U6 `( B: X2 s 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
; q4 f7 r s! g: j) M" l
; u. e% ?) ], Y6 g( C3 m 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 : W; r7 B% o' }. U5 w$ I, X5 w8 T& w
( s5 e$ I/ f6 M+ o 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 , S% t9 Z5 Z, v; j1 U
" W j2 S6 I+ H4 i7 t" C6 A4 X
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
# i5 s" q2 ~; [2 t: I' J b& ^, K9 z3 ]% M6 w% O
Bylund DMchutchison J. Autoimmune liver diseaes. Clin LabMED, 1997, 17: 483一497. . ~+ }9 [' H- H b6 D5 a
& r4 Y3 Y& y! @! \
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
7 z3 w0 l, w. C$ n( B! w2 N: k& a4 t; }9 C/ o) [5 _
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 " J" t# R; N; ?. B
! {+ Z( |- o& g9 _! r Courvalin JC, Worman I{I. Nuclear envelop protein autoanti-bodies in primary biliary cirrhosis. Semin Liver Dis 1997.17:79一90
6 X% r K1 Y# f$ l: U3 P8 n
9 V( M1 n4 R$ ~% V) ^$ C. _: e 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 % ~5 a" U" O% O% m
# O, i7 k) [2 E, {* L
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
& r& W* J8 `* K+ q6 E. ^1 r9 g& ~& g/ H( ?0 j2 {
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 4 {6 s, }1 t+ ? x" V
" }; Y0 Y! g5 c8 h6 \% v" {/ }
Czaj a川,Ming C,Shirai M, et al. Frequency and significanceof antibodies to histones in autoimmune hepatitis. J HEpatol1995.23:32一38 + y, O8 f: W( f9 {
3 Q R& [' O& s- [* D5 ?
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 : e/ N! V. t2 C2 y# ~& @ Q
% J+ r- c7 F0 a, E0 ~9 h 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
/ }* {* S0 ^. f- W, ?
) b1 v3 r" m( W& E! \ 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 ) }* Z0 i2 w+ L0 h
4 R- |- H4 l, {
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
y7 W! k7 N& c% r2 h' n; F0 }9 Q9 {7 m3 X
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 2 _- i& W: d0 q3 }! ~& n' Y
' R- I7 t# N c t
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 ~$ p& _5 n P6 n9 }1 U* w
9 `% Y& F3 X( Y. N
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
) K% Y. S- P* c0 b% c5 Y
: S$ B3 |0 b+ L) t8 ^. M 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 5 ]* I! G( \9 D/ u" z$ B
( D& X& z& F0 n4 K; e1 I$ D
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 1 y7 [, Y/ M( c; f& _
' _* n" F- e l 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 # C5 ]7 W# R, `9 B1 R! T
5 t+ k' t" C6 _/ G9 B0 I LaBrecque DR, Phillips MJP, lppolito LA, et al. Antineu-trolphil cytoplasmic antibody and chronic liver disease(abstr ).HEpatology, 1999.30:428A
) _6 O5 `+ j8 c) Q3 L0 w6 Y
- m4 l0 H4 {, l8 U 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 : Q8 n( ^4 |. P
" n& X0 \5 d2 U 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
8 Y Y0 B) ~; O0 V' S$ b
2 u# b/ l# |# k" t& M% w3 N 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
% l8 R- o% w1 u: H& `2 s
3 z# a& M$ j! @ McFarlane IG. The relationship between autoimmune mark-ers and different clinical syndromes in autoimmune hepatitis. Gut,1998.42:599一602
0 w6 @, P- `0 n% u0 e. |( Z5 U6 r- z% ?# k4 I
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
; N2 U9 _ z0 r9 P5 L) ` ]! z
2 v* m" A8 |" q) R Michael P. Manna and Christian P. Strassburg. Autoimmunehepatitis: clinical challenges. Gastroenterology,2001.120:1502-1517 4 J& F# o- W- c7 _ R
& x+ ^4 t3 _' J( v, y; n
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
; Z; ]* B" u* F- r
: f2 n- t" `% V5 S" v) ] 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 9 R: N4 j: ?# [& J0 G: y
! ~* @) W$ @! C; s. a Onouchi H, Muro Y, Tomita Y. Clinical features and tgGsubclass distribution of anti-p80 coilin antibodies. J Autoimmun,1999.13:225一232
+ A! H1 g; X: Q r: n( y$ c2 I! `$ |8 T# G8 {" U+ t( S
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 + C( z" i$ X C: O% o: ]! n+ H/ j* T
2 p1 V& b. i. m, m% J6 ^ H' P
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
9 d2 n* u6 [5 f9 y9 v- ^. w' T. O/ X5 B9 U: Q( 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 - T1 t" ^+ \: y( z" p
, n+ b$ C. d3 y2 X
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
_, O' d7 K) D& a6 G8 L: N/ O
; p: W9 ^- V, P; m3 ^1 p0 s. k0 H 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 7 f, z# |2 I8 N- W% k
; j; [# C2 ]% W3 S$ s' ~9 `: d 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 7 \* l- @; h5 G- l+ M; W7 q) C
g# n6 n3 |/ P* \2 k: u$ }
Treichel U,Porallat,Hess G, et al. Autoantibodies to humanasialoglycoprotein receptor in autoimmune-type chronic hepatitis.HEpatology,1990.11:606一612 ) _. W1 [- Y. p" N ]2 l
3 y2 m% z: u2 x6 W9 ~& h
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' C, E- {% w3 W
/ l) J3 b9 R; v. `1 G 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
, d' w$ [- X7 f: w% c+ ]9 S9 x! q/ c, {' W( \; v+ U
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
" q) M) u9 e& E; c9 F
. F( L4 _, @: m 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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