Антифосфолипидный синдром - часть 59

риска необъяснимых ранних спонтанных абортов. Кроме того, по дан

ным проспективного исследования, обнаружение этих веществ было

связано со значительным риском потери плода при последующих бере

менностях. 

Показания для определения аФЛ и алгоритм лабораторного обсле

дования пациентов с подозрением на АФС представлены на рисунке 8.1

и в таблице 8.15.

241

Подозрение на АФС

АИТВ

Удлинение

Смешивание

ФосфолипидB

зависимость

аФМ ИФМ (+)

аФМ ИФМ (+)

Достоверный

АФС

Специфические

ингибиторы

Определение

факторов

АФС

маловероятен

Определение

факторов

Дефицит

факторов

КВС или

dRVVT

ВА (—)

аФЛ ИМФ (—)

ВА (—)

аФЛ (—)

Рис. 8.1. Алгоритм лабораторной диагностики АФС

Коррекция

ГЛАВА 8. Клиническое значение антифосфолипидных антител

ЛИТЕРАТУРА

Насонов Е.Л. Антифосфолипидный синдром

242

• Необъяснимый спонтанный аборт

или внутриутробная гибель плода 
после 10й недели беременности

• Выраженная задержка роста плода
• Тяжелая преэклампсия до 34й 

недели беременности

• 2 и более необъяснимых спонтан

ных аборта до 10й недели бере
менности

• Ложноположительная реакция Вассер

мана

• Тромбоэмболии в анамнезе
• Инсульт
• СКВ
• Гемолитическая анемия
• Транзиторные ишемические атаки и по

теря зрения

• Сетчатое ливедо
• Необъяснимое удлинение АЧТВ
• Необъяснимая тромбоцитопения
• Положительная реакция на АНФ
• Семейный анамнез АФС
• Атипичные признаки раннего склероза

Таблица 8.15. Показания к определению аФЛ

У женщин

У мужчин и женщин

1. Reddel SW, Krilis SA. Testing for and clinical

significance of anticardiolipin antibodies. Clin
Diagn Lab Imunol 1999; 6: 775—782.

2. Roubey, RA. Immunology of the antiphospho

lipid antibody syndrome. Arthritis Rheum 1996;
39: 1444.

3. Triplet DA. Antiphospholipid antibodies. Arch

Pathol Lab Med 2002; 126: 1424—1429.

4. Galli M, Barbui T. Prevalence of different

antiphospholipid antibodies in systemic lupus ery
thematosus and their relationship with the
antiphospholipid syndrome. Clin Chem 2001; 47:
985—987.

5. Strandberg Pederrsen N, Orum O, Mouritsen

S. Enzymelinked immunosorbent assay for
detection of antibodies to the veneral disease
research laboratory (VDRL) antigen in syphilis. J
Clin Microbiol 1987; 25: 1711—1716.

6. Sammaritano LR, Gharavi AE, Lockshin

MD. Antiphospholipid antibody syndrome:
Immunologic and clinical aspects. Semin Arthritis
Rheum 1990; 20: 81.

7. Triplett DA, Brandt JT, Musgrave KA.

Relationship between lupus anticoagulants and

antibodies to phospholipids. JAMA 1988; 259:
550.

8. Hanly JG, Kandiah D, Kouts S. et al. Detect

ion of "antiphospholipid antibodies" using a chro
mogenic assay thrombin generation. Lupus 1998;
7: 219 (abstract).

9. Pierangeli SS, M. SLK Silva, Harris EN. An

antiphospholipid workshop: 7

th

International

Symposium on Antiphospholipid Antibodies. J
Rheumatol 1998; 25:156—160.

10. Harris EN. The second intenational anti

cardiolipin standartisation workshop. The
Kingston antiphospholipid study (KAPS) group.
Am J Clin Pathol 1990; 94: 476—484.

11. Александрова ЕН, Насонов ЕЛ, Ковалев

В.Ю. Количественный иммуноферментный
метод определения антител к кардиолипину в
сыворотке крови. Клиническая ревматол.
1995; 4: 35—39.

12. Tincani A, Balestrieri G, Allegri F. et al.

Overview on anticardiolipin ELISA standartiza
tion. J Autoimmunity 2000; 15: 195—197.

13. AlarconSegovia D, Deleze M, Oria CV, et

al. Antiphospholipid antibodies and the antiphos

243

pholipid syndrome in systemic lupus erythemato
sus. A prospective analysis of 500 consecutive
patients. Medicine 1989; 68: 353—365.

14. Escalante A, Brey RL, Mitchell BD, et al.

Accuracy of anticardiolipin antibodies in identify
ing a history of thrombosis among patients with
systemic lupus erythematosus. Am J Med 1995;
98: 559—565.

15. Wasmuth JC, Minarro DO, Homrighausen

A, et al. Phoshpholipid autoantibodies and the
antiphospholipid antibody syndrome: diagnostic
accuracy of 23 methods studied by variation in
ROC curves with number of clinical manifesta
tions. Clin Chem 2002; 48: 1004—1010.

16. Musial J, Swadzba J, Motyl A, et al.

Clinical significance of antiphospholipid protein
antibodies. Receiver operating characteristics plot
analysis. J Rheumatol 2003; 30: 723—730.

17. Reber G, Arvieux J, Comby E, et al.

Multicenter evaluation of nine commercial kits for
the quantitation of anticardiolipin antibodies. The
working group on methodologies in haemostasis
from the GEHT (groupe d'Etudes sur le hemosta
sis et la thrombose). Thromb Haemostasis 1995;
73: 444—452.

18. Andrian MA, Colonna F, Morio F, et al.

Comparison of different kits in the detection of
autoantibodies to cardiolipin and beta2 glycoprotein
1. Rheumatology (Oxford). 2004; 43:181—185.

19. McNeil HP, Chesterman CN, Krilis SA, et

al. Immunology and clinical importance of
antiphospholipid antibodies. Adv Immunol 1991;
49:193—280.

20. Boffa MC, Berard M, Sugi T, et al. Anti

phosphatidulethanolamine antibodies as the only
antiphospholipid antibodies detected by ELISA II
Kininigen reactivity. J Rheumatol 1996; 23:
1375—1379.

21. Harris EN, Pierangeli SS. "Equivocal"

antiphospholipid syndrome. J Autoimmunity
2000; 15: 81—85.

22. Day HM, Thiagarajan P, Ahn C, et al.

Antibodies to 

β

2

glycoprotein I in systemic lupus

erythehematosus and primary antiphospholipid
syndrome: clinical correlations in comparison with
other antiphospholipid antibody tests. J Rheu
matol 1998; 25: 667—674.

23. Matsuura E, Igarashi Y, Fujimoto M, et al.

Heterogeneity of anticardiolipin antibodies

defined by the anticardiolipin cofactor. J Immunol
1992; 148: 3885—3891.

24. Hasselaar P, Triplett DA, La Rue A, et al.

Heat treatment of serum and plasma induces false
positive results in the antiphospholipid antibody
ELISA. J Rheumatol 1990; 17: 186—191.

25. Cabiedes J, Cabral AR, AlarconSegovia D.

Hidden antiphospholipid antibodies in normal
human sera circulate as immune complexes whose
antigen can be removed by heat, acid, hipermolar
buffers or phospholipase treatment. Eur J
Rhumatol 1998; 28: 2108—2114.

26. Matsuda J, Saiton N, Gohchi K, et al.

Distinguising 

β

2

glycoprotein I dependent (sys

temic lupus erithematosus type) and independent
(syphilis type) anticardiolipin antibody witch
tween 20. Br J Haematol 1993; 85: 799—802.

27. Arvieux J, Roussel B. Influence of Tween 20

on the detection of 

β

2

glycoprotein I  dependent

anticardiolipin antibodies. Br J Haematol 1994;
87: 443—444.

28. Cabral AR, Cabiedes J, AlarconSegovia

D. Tween20 detaches cardiolipin from ELISA
plates and maker anticardiolipin antibodies
undetectable regardless of the presence of 

β

2

gly

coprotein I. J Immunol Methods 1994; 175:
107—114.

29. Hunt JE, McNeil HB, Morgan GJ, et al. A

phospholipid

β

2

glycoproteinI complex is an

antigen for anticardiolipin antibodies occurring in
autoimmune disease but not with infection. Lupus
1992; 1: 75—81.

30. Arvieux J, Darnige L, Hachulla E, et al.

Species specificity of anti

β

2

glycoproteinI auto

antibodies and its relevance to anticardiolipin
antibody quantitation. Thromb Haemostasis
1996; 75: 725—730.

31. McNeil HP, Simpson RJ, Chesterman CN,

Krilis SA. Antiphospholipid antibodies are direct
ed against a complex antigen that includes a lipid
binding inhibitor of coagulation: 

β

2

glycoprotein

I (apoliprotein H). Proc Natl Acad Sci USA.
1990; 87: 4120—4124.

32. Roubey RA. Antigenic specifities of antiphos

pholipid antibodies implications for clinical labo
ratory testing and diagnosis of the antiphospho
lipid syndrome. Lupus 1996; 5: 425—430.

33. McCarthy JM, Wagenknecht DR., McIntyre

J.A. Activity of antiphospholipid antibody ELISA

ГЛАВА 8. Клиническое значение антифосфолипидных антител

Насонов Е.Л. Антифосфолипидный синдром

244

cofactor in different animal sera. J Clin Lab Anal
1994; 8: 167—171.

34. Matsuura E, Igarashi Y, Yasuda T, Triplett

D, Koike T. Anticardiolipin antibodies recognize
beta 2glycoprotein I structure altered by inter
acting with an oxygen modified solid phase sur
face. J Exp Med 1994; 179: 457—462.

35. Pengo V, Biasolo A, Brocco T, Tonetto S,

Ruffatti A. Autoantibodies to phospholipid binding
plasma proteins in patients with thrombosis and
phospholipidreactive antibodies. Thromb
Haemost 1996; 75: 721—724.

36. Roubey RAS, Eisenberg RA., Harper MF,

Winfield JB. "Anticardiolipin" autoantibodies
recognize beta2glycoprotein I in the absence of
phospholipid. Importance of antigen density and
bivalent binding. J Immunol 1995: 154: 954—
960.

37. Hunt J, Krilis S. The fifth domain of beta2

glycoprotein I containes a phosphilipid binding
site (cys

281

cys

288

), and region recognised by anti

cardiolipin antibodies. J Immunol 1994;152:
653—659.

38. OhKura N, Magihara Y, Yoshimura T, et

al. Plasmin can reduse the function of human 

β

2



glycoprotein I by clearity domain V into a nicked
form. Blood 1998; 91: 4173—4179.

39. Arvieux J, Regnault V, Hachulla E, et al.

Heterogeneity and immunochemical properties of
antibeta2glycoproteinI autoantibodies. Thromb
Haemostasis 1998; 80: 393—398.

40. Guerin J, Feighery C, Sim RB, et al.

Antibodies to 

β

2

glycoprotein1 A specific marker

for the antiphospholipid syndrome. Clin Exp
Immunol 1997; 109: 304—309.

41. Forastiero RR, Martinuzzo ME, Cerrato

GS, et al. Relationship of anti

β

2

glycoprotein I

and antiprothrombin antibodies to thrombosis and
pregnancy loss in patients with antiphospholipid
antibodies. Thromb Haemost 1997; 78:1008—
1014.

42. Koike T, Matsuura E. Anti

β

2

glycoprotein

I antibodie: specificity and clinical significance.
Lupus 1996; 5: 378—380.

43. Sheng Y, Kandiah DA., Krilis SA. et al.

Anti

β

2

glycoprotein I antibodies from patients

with the "antiphospholipid" syndrome bind to 

β

2



glycoprotein I witch low affinity dimerization of
β

2

glycoprotein I induces a significant increase in

anti

β

2

glycoproteinI antibody affinity. J

Immunol 1998; 161: 2038—2043.

44. Vlachoyiannopoulos PG, Petrovas C,

Tektonidou M, et al. Antibodies to 

β

2

glycopro

teinI: urea resistance binding specificity and
association with thrombosis. J Clin Immunol
1999; 18: 380—391.

45. Molina JF, GutierrezUrena S, Molina J, et

al. Variability of anticardiolipin antibody isotype
distribution in 3 geographic populations of
patients with systemic lupus erythematosus. J
Rheumatol 1997; 24: 291—296.

46. Cucurul E, Gharavi AE, Diri E, et al. IgA

anticardiolipin and anti

β

2

glycoprpteinI are

the most prevalent isotypes in African American
patients with systemic lupus erythematosus. Am J
Med Sci 1999; 418: 55—60.

47. Samarkos M, Asherson RA, Loizou S. The

clinical significance of IgA antiphospholipid anti
bodies. J Rheumatol 2001; 28; 694—697.

48. Bizzaro N, Pasini P, Finco B. Falsepositive

reactions for IgA antiphospholipid and anti

β

2



glycoproteinI antibodies in patients with IgA
monoclonal gammapathy. Clin Chem 1999; 45:
2007—2010.

49. Hanly JG, Hong C, James H, Mansour M,

Jones JV. Requirement of 

β

2

glycoproteinI as

cofactor in the binding for IgM and IgA anticardi
olipin antibodies. J Rheumatol 1995; 22: 1091—
1096.

50. Gharavi AE, Harris EN, Asherson RA,

Hughes GR. Anticardiolipin antibodies: isotype
distribution and phospholipid stecificity. Ann
Rheum Dis 1987; 46: 1—6.

51. SelvaO`Callaghan A, OrdiRos J,

MonegalFerran F, et al. IgA anticardiolipin
antibodies — relation with other antiphospholipid
antibodies and clinical significance, Thromb
Haemost 1998; 79: 282—285.

52. Weidmann CE, Wallace DJ, Peter JB, et al.

IgG, IgM and IgA antiphospholipid antibody iso
types in systemic lupus erythematosus. J
Rheumatol 1988; 15: 74—79.

53. Hamilton RG. Human IgG subclasss meas

urement in the clinical laboratory. Clin Chem
1987; 33: 1707—1725.

54. Gharavi AE, Harris EN, Lockshin MD, et

al. IgG subclass and light chain distribution of
anticardiolipinn and antiDNA antibodies in sys