Bearded Collie Auto Immune Disease Genetics Co Efficients of Inbreeding Way Forward
Beardies Past, Present and Future
Co efficients of Inbreeding for Dummies
An explanation of what COIs are and what they mean
Gap Analysis Report
Basic Beardie Genetics
Effective Population Size
Bearded collie. dangers of low population size
Bottleneck Sires
Auto Immune Disease
Addison's Disease
Addison's Disease Update
Auto Immune Haemolytic Anaemia
Symetrical Lupoid Onchodystrophy (SLO)
Immune Mediated Hypothyroidism
Idiopathic Thrombocytopenia Purpura
Useful links to other websites
The Cohort Study
This page describes the study that will collect comprehensive and valuable data on the health and welfare of the Bearded Collie.
Dilated Cardiomyopathy
questions the possibility of some instances of DCM being auto immune problem

Dilated Cardiomyopathy

Is cardiomyopathy an autoimmune disease? Michael Fu and Shinobu Matsui1 Wallenberg Laboratory, Sahlgrenska University Hospital, Go ¨teborg, Sweden, 1Department of Cardiology Kanazawa Medical University, Kanazawa, Japan

Idiopathic dilated cardiomyopathy (DCM) is one of the leading causes of severe heart failure and the most common cause of heart transplantation due to its ventricular dilatations and contractile dysfuntions. Twenty percent of DCM is in the familiar form and the rest is sporadic. The clinical impact of DCM is far greater than its position in epidemiological terms. Despite recent improvements in therapy, both incidence and mortality are still very high. The main problem is its heterogeneous etiology. So far, three factors have been identified to be potentially important: enteroviral infection, immune mechanism and genetic factors. It is plausible that a subgroup of DCM is a post-infectious autoimmune disease, especially with individuals with genetic susceptibility.


Evidence from clinical findings indicating existence of autoimmunity

During last 10 years there have been many investigations showing distinct autoantibodies or other immune factors in heterogeneous subsets of DCM which have contributed supportive and confounding evidence to a hypothesis that multiple autoimmune mechanisms are involved in DCM. In DCM and myocarditis, abnormalities in cell-mediated immunity have been clinically demonstrated by the findings of an altered lymphocyte function, altered relative proportions of lymphocyte subsets, an activated immune cytokine system, the in

appropriate expression of the major histocompatibility complex on cardiac tissue and expression of adhesion molecles on cardiac myocytes.1–9 The relative contribution of cellular and humoral immune disturbances to the pathogenesis of myocyte injury in various heart diseases has not been determined. Accumulated evidence hitherto demonstrated a variety of circulating autoantibodies in the sera of patients with DCM. The list can be long, notably including autoantibodies directed against the myosin,6,10–14 mitochondrial adenine nucleotide translocator and M7,15–18 the branched chain alpha-ketoacid dehydrogenase dihydrolipoyl transacylase (BCKD-E2),19 laminin,20 b-adrenoceptors,21–26 M2 muscarinic receptors,25–27 sarcolemmal Na-K-ATPase28 and heat shock protein29 respectively. Since Venter et al. reported autoantibodes against b2-adrenoceptors in allergic rhinitis and asthma in 1980,30 there is a great amount of evidence available describing autoantibodies against b1-adrenoceptors in patients with DCM. Wallukat and Wollenberger found in 1987 that the IgG fraction of patients with DCM was able to display positive chronotropic effect on cultured neonatal rat myocytes.22 By using the ligand bindings of DCM sera on rat cardiac membranes, Limas et al. demonstrated autoantibodies against b-adrenergic receptors in 40% of patients with DCM.31 Magnusson et al., by using synthetic peptides corresponding to the second extracellular loops of human b1- and b2adrenergic receptors as coated antigens in an enzymelinked immunosorbent assay (ELISA), found autoantibodies against b1-adrenergic receptor peptide in 31% of patients with DCM but no autoantibodies against b2adrenergic receptor peptide.24 We have demonstrated for the first time that the sera from patients with DCM recognized the M2 muscarinic receptor peptide (36– 37%).25–27 Further study demonstrated that anti-M2 muscarinic receptor and b1-adrenoceptor autoantibodies have an almost identical spectrum of frequencies of occurrence in patients with DCM despite different geographical origins from Japan, China and Sweden.25–27,32 Moreover, anti-b1-adrenoceptor autoantibodies are mainly present in DCM but not in hypertension25 and valvular heart disease.33 On the contrary, autoantibodies against the a1-adrenoceptors and AT1 receptors were demonstrated mainly in hypertension (64% and 44% of cases, respectively).34,35 Although it has been shown that anti-muscarinic receptors and b1-adrenoceptor autoantibodies are more common in DCM compared with other antireceptor autoantibodies, it does not mean that these antireceptor autoantibodies are only specific for DCM since there are only limited data available from antibody screenings from other cardiovascular diseases and/or by use of other autoantigens. Recently we have shown that, in

aortic banding- and adriamycin-treated rats, the frequencies and titers of autoantibodies to the muscarinic receptor and b1-adrenoceptor were increased when myocardial remodeling occurred, suggesting that cardiac remodeling itself, in two disparate models of cardiomyopathy, was able to trigger the genesis of antireceptor autoantibodies.36 Therefore anti-muscarinic receptor and b1-adrenoceptor autoantibodies are possibly triggered by myocardial remodeling in patients with DCM. This may explain why there are also antimuscarinic receptor and b1-autoantibodies adrenoceptor in about 40% of patients with chronic Chagas’ infection.37 But this does not rule out that anti-muscarinic receptor and b1-adrenoceptor autoantibodies can be pathogenic and play an important role in the progression, instead of initiation, of cardiomyopathy and heart failure, and as long as they are functionally active invivo and persist over a certain period they may contribute to the pathophysiology of the disease. For example, viral infection can induce myocardial damage which in turn triggers antibody production which can escalate to aggravate myocardial damage. It is worthwhile to point out that antibody production may be triggered due to myocardial injury secondary to ischemia because of alteration of self-antigens that are normally sequestered from the immune system. Therefore, whether autoantibodies play an important role in the development of disease depends on the availability of sustained antigen exposure, properties of autoantibodies in immunological, biochemical and kinetic aspects and other genetic factors as well as subclasses in serum of autoantibodies. Recently, Jahns et al. showed that anti b1-adrenoceptor antibodies from six of eight patients with DCM act as receptor-sensitizing agents whereas two of eight acts as partial agonists,38 and Warraich et al. showed that IgG3 is probably more important than other subclasses in mediating DCM.39
Evidence from in-vitro studies
Low titers of autoantibodies, which can be part of the normal immunologic repertoire, are not necessarily pathogenic.32 Functional characterization of an antibody is the first step toward defining the role of the antibody in the development of disease. Wallukat et al. demonstrated that the IgG fractions of patients with DCM were able to increase the beating rate of myocytes.22,40 Limas et al. found that positive sera from DCM were able to immunoprecipitate b-adrenergic receptors and to inhibit adenylyl cyclase activity.31 Magnusson et al. demonstrated that purified autoantibodies can not only decrease the the binding sites but also recognize the target receptors by both immunobloting and immunocytochemistry.24,41 Krause et al. demonstrated that autoantibodies against b1-adrenergic

receptors from DCM were able to increase the activity of cAMP-dependent protein kinase (PKA).42 Likewise, we have demonstrated specific localization of muscarinic receptors in the human myocardium from DCM using anti-M2 muscarinic receptor autoantibodies, thus suggesting that autoantibodies can interact with their target receptors in failing heart tissue. In addition, anti b1 adrenergic receptor and M2 muscarinic receptor autoantibodies from DCM patients displayed positive and negative chronotropic effects respectively, which were resistent to desensitization, being different from the classical b-adrenergic receptor agonist isoprenaline and the muscarinic receptor agonist carbachol which can induce desensitization after the short a period of time.41,43,44
Evidence from in vivo studies
According to the definition of autoimmune disease as suggested by Rose and Bona (1993),45 it is not enough to define DCM as an autoimmune disease although our and others’ previous data have shown functional activities of autoantibodies in vitro. Direct evidence is still needed in vivo to make sure that cardiomyopathy can be reproduced in animals by autoimmunity, either by passive transfering of immune components from patients with DCM to SCID (Severely Combined Immunodeficieny) mice or by chronic active immunization of animals with autoantigens. Schwimmbeck et al. successfully transfered peripheral blood leukocytes of patients with chronic myocarditis into SCID mice that developed human cellular infiltrates of the myocardium and an impairment of the left ventricular function.46 Another study from our laboratory showed that transfer of lymphocytes from patients with DCM to SCID mice demonstrated induced unfavourable remodeling and increased myocardial fibrosis.47 By use of active immunization with receptor peptide(s) during 1 year, it was shown that both groups of rabbits immunized with either the b1-adrenoceptor peptide or the M2 muscarinic receptor peptide displayed significantly enlarged ventricles and thinner walls, as compared with the control group. When immunization was performed using combined b1 and M2 receptor peptides, cardiac hypertrophy was seen. Moreover, microscopic examinations of the rabbit hearts from both immunized groups demonstrated mainly degenerative changes.48–50 Recently, Iwata et al. used a similar protocol but in only 6 months demonstrated myocardial hypertroph, b1-adrenoceptor receptor desensitization, increased Gi protein and Gprotein-coupled receptor kinase-5 expression in association with myocyte disorganization and interstitial fibrosis.51,52

Evidence from therapeutical approaches

Theoretically, autoimmune therapy should be aimed at modulating the immune system to inhibit antibody production and at blocking the active autoantibodies of pathogenic importance. In order to restore normal immune function, it necessitates elucidation of mechanisms for initiation, development and regulation of autoimmunity including genetic factors, cytokines, heat shock proteins etc. Unfortunately this mechanism has not been fully understood yet. Therefore current autoimmune therapy is focused more upon inhibiting antibody activity and elimination of antibodies. For example, Matsui et al. has shown that the b1-receptor blocker bisoprolol was able to prevent autoimmune injury by b1-receptor antibody.52 Immunoadsorption has been and still is a heated topic. Several studies have demonstrated that immunoadsorption can improve cardiac functions.53–56 The underlying mechanisms for favourable effects on cardiac function remain unsolved. It has been postulated that antireceptor autoantibodies play an important role.52,53,57,58 Our data from antibody analyses of immunoadsorption, however, demonstrated that elimination of antireceptor autoantibodies may be important but not the only explanation. A recent study by Felix et al. showed that removal of circulating negative inotropic autoantibodies may contribute to the early beneficial hemodynamic effect of immunoadsorption.59 However, the specific antigen(s) to these negative inotropic autoantibodies have not been clarified. Another studybyStaudt et al. demonstrated that immunoadsorption can ameliorate myocardial inflammation.56 The above therapeutic approaches add further weight to the hypothesis that cardiomyopathy is autoimmunitymediated.
A Subgroup of Cardiomyopathy Is Autoimmune Disease Related
To summarize the data available from both in-vitro and in-vivo studies of antireceptor autoantibodies as well as from other autoantibodies and autoreactive lymphocytes, it is evident that a subgroup of DCM is autoimmunity-mediated. This is understandable because DCM is heterogeneous, implying that different subgroups of DCM may have different pathogeneses. It may be practical in the future to separate ‘‘autoimmune cardiomyopathy’’ from other ‘‘idiopathic’’ DCM.


1. Fowles RE, Bieber CP, Stinson EB: Defective in vitro suppressor cell function in idiopathic congestive cardiomyopathy. Circulation 1979; 59: 483–491

2. Eckstein R, Mempel W, Bolte HD: Reduced suppressor cell activity in congestive cardiomyopathy and in myocarditis. Circulation 1982; 65: 1224–1229
3. Anderson JL, Carlquist JF, Hammond EH: Deficient natural killer cell activity in patients with idiopathic dilated cardiomyopathy. Lancet 1982; 2: 1124–1127
4. Sanderson JE, Koech D, Iha D, Ojiambo HP: T-lymphocyte subsets in idiopathic dilated cardiomyopathy. Am J Cardiol 1985; 55: 755–758
5. Ro ¨nnblom LE, Forsberg H, Evrin PE: Increased level of HLADR-expressing T lymphocytes in peripheral blood from patients with idiopathic dilated cardiomyopathy. Cardiology 1991; 78: 161–167
6. Caforio AL, Stewart JT, Bonifacio E, Burke M, Davies MJ, McKenna WJ, Bottazzo GF: Inappropriate major histocompatibility complex expression on cardiac tissue in dilated cardiomyopathy. Relevance for autoimmunity? J Autoimmun 1990; 3: 187–200
7. Koike S: Immunological disorders in patients with dilated cardiomyopathy. With special reference to the production of interleukin-2 and the expression of interleukin-2 receptors in the patients’ peripheral blood lymphocytes. Jpn Heart J 1989; 30: 799–807
8. Seko Y, Yamazaki T, Shinkai Y, Yagita H, Okumura K, Naito S, Imataka K, Fujii J, Yazaki Y: Cellular and molecular bases for the immunopathology of the myocardial cell damage involved in acute viral myocarditis with special reference to dilated cardiomyopathy. Jpn Circ J 1992; 56: 1062–1072
9. Toyozaki T, Saito T, Takano H, Yorimitsu K, Kobayashi S, Ichikawa H, Takeda K, Inagaki Y: Expression of intercellular adhesion molecule-1 on cardiac myocytes for myocarditis before and during immunosuppressive therapy. Am J Cardiol 1993; 72: 441–444
10. Das SK, Cassidy JT, Petty RE: Antibodies against heart muscle and nuclear constituents in cardiomyopathy. Am Heart J 1972; 83: 159–166
11. Caforio AL, Grazzini M, Mann JM, Keeling PJ, Bottazzo GF, McKenna WJ, Schiaffino S: Identification of alpha- and betacardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy. Circulation 1992; 85: 1734–1742
12. Caforio AL, Mahon NJ, Mckenna WJ: Cardiac autoantibodies to myosin and other heart-specific autoantigens in myocarditis and dilated cardiomyopathy. Autoimmunity 2001; 34: 199–204
13. Latif N, Baker CS, Dunn MJ, Rose ML, Brady P, Yacoub MH: Frequency and specificity of antiheart antibodies in patients with dilated cardiomyopathy detected using SDS-PAGE and western blotting. J Am Coll Cardiol 1993; 22: 1378–1384
14. Neumann DA, Burek CL, Baughman KL, Rose NR, Herskowitz A: Circulating heart-reactive antibodies in patients with myocarditis or cardiomyopathy. J Am Coll Cardiol 1990; 16: 839– 846
15. Schultheiss HP, Schwimmbeck P, Bolte HD, Klingenberg M: The antigenic characteristics and the significance of the adenine nucleotide translocator as a major autoantigen to antimitochondrial antibodies in dilated cardiomyopathy. Adv Myocardiol 1985; 6: 311–327
16. Schulze K, Becker BF, Schauer R, Schultheiss HP: Antibodies to ADP-ATP carrier – an autoantigen in myocarditis and dilated cardiomyopathy – impair cardiac function. Circulation 1990; 81: 959–969
17. Ansari AA, Herskowitz A, Danner DJ: Identification of mitochondrial proteins that serve as targets for autoimmunity in human dilated cardiomyopathy. Circulation 1988; 78 suppl: 457
18. Klein R, Maisch B, Kochsiek K, Berg PA: Demonstration of organ specific antibodies against heart mitochondria (anti-M7) in

sera from patients with some forms of heart diseases. Clin Exp Immunol 1984; 58: 283–292
19. Ansari AA, Neckelmann N, Villinger F, Leung P, Danner DJ, Brar SS, Zhao S, Gravanis MB, Mayne A, Gershwin ME, et al: Epitope mapping of the branched chain alpha-ketoacid dehydrogenase dihydrolipoyl transacylase (BCKD-E2) protein that reacts with sera from patients with idiopathic dilated cardiomyopathy. J Immunol 1994; 153: 4754–4765
20. Wolff PG, Kuhl U, Schultheiss HP: Laminin distribution and autoantibodies to laminin in dilated cardiomyopathy and myocarditis. Am Heart J 1989; 117: 1303–1309
21. Sterin-Borda L, Cremaschi G, Pascual J, Genaro A, Borda E: Alloimmune IgG binds and modulates cardiac betaadrenoceptor activity. Clin Exp Immunol 1984; 58: 223–228 22. Wallukat G, Wollenberger A: Effects of the serum gamma globulin fraction of patients with allergic asthma and dilated cardiomyopathy on chronotropic beta adrenoceptor function in cultured neonatal rat heart myocytes. Biomed Biochim Acta 1987; 46: S634–639
23. Limas CJ, Limas C, Kubo SH, Olivari MT: Anti-b-receptor antibodies in human dilated cardiomyopathy and correlation with HLA-DR antigens. Am J Cardiol 1990; 65: 483–487 24. Magnusson Y, Marullo S, Hoyer S, Waagstein F, Andersson B, Vahlne A, Guillet JG, Strosberg AD, Hjalmarson A, Hoebeke J: Mapping of a functional autoimmune epitope on the b1adrenergic receptor in patients with idiopathic dilated cardiomyopathy. J Clin Invest 1990; 86: 1658–1663
25. Fu ML, Hoebeke J, Matsui S, Matoba M, Magnusson Y, Hedner T, Herlitz H, Hjalmarson A ˚ : Autoantibodies against cardiac Gprotein-coupled receptors define different populations with cardiomyopathies but not with hypertension. Clin Immunol Immunopathol 1994; 72: 15–20
26. Matsui S, Fu ML, Shimizu M, Fukuoka T, Teraoka K, Takekoshi N, Murakami E, Hjalmarson A ˚ : Dilated cardiomyopathy defines serum autoantibodies against G-protein-coupled cardiovascular receptors. Autoimmunity 1995; 21: 85–88
27. Fu LX, Magnusson Y, Bergh CH, Liljeqvist JA ˚ , Waagstein F, Hjalmarson A ˚ , Hoebeke J: Localization of a functional autoimmune epitope on the muscarinic acetylcholine receptor-2 in patients with idiopathic dilated cardiomyopathy. J Clin Invest 1993; 91: 1964–1968
28. Baba A, Yoshikawa T, Mitamura H, Akaishi M, Ogawa S: Autoantibodies against sarcolemmal Na-K-ATPase in patients with dilated cardiomyopathy: autoimmune basis for ventricular arrhythmias in patients with congestive heart failure: J Cardiol 2002; 39: 50–51 (In Japanese)
29. Mandi Y, Hogye M, Talha EM, Skolak E, Csanady M: Cytokine production and antibodies against heat shock protein 60 in cardiomyopathies of different origins. Pathobiology 2000; 68: 150– 158
30. Venter JC, Fraser CM, Harrison LC: Autoantibodies to b2adrenergic receptors: a possible cause of adrenergic hyporesponsiveness in allergic rhinitis and asthma. Science 1980; 207: 1361–1363
31. Limas CJ, Goldenberg IF, Limas C: Autoantibodies against badrenoceptors in human idiopathic dilated cardiomyopathy. Circ Res 1989; 64: 97–103
32. Liu HR, Zhao RR, Zhi JM, Wu BW, Fu ML: Screening of serum autoantibodies to cardiac beta1-adrenoceptors and M2muscarinic acetylcholine receptors in 408 healthy subjects of varying ages. Autoimmunity 1999; 29: 43–51
33. Jahns R, Boivin V, Siegmund C, Boege F, Lohse MJ, Inselmann G: Activating beta-1-adrenoceptor antibodies are not associated with cardiomyopathies secondary to valvular or hypertensive heart disease. J Am Coll Cardiol 1999; 34: 1545–1551 34. Fu ML, Herlitz H, Wallukat G, Hilme E, Hedner T, Hoebeke J,

Hjalmarson A ˚ : Functional autoimmune epitope on alpha 1adrenergic receptors in patients with malignant hypertension. Lancet 1994; 344: 1660–1663
35. Fu ML, Herlitz H, Schulze W, Wallukat G, Micke P, Eftekhari P, Sjogren KG, Hjalmarson A, Muller-Esterl W, Hoebeke J: Autoantibodies against the angiotensin receptor (AT1) in patients with hypertension. J Hypertens 2000; 18: 945–953
36. Liu HR, Zhao RR, Jiao XY, Wang YY, Fu M: Relationship of myocardial remodeling to the genesis of serum autoantibodies to cardiac beta(1)-adrenoceptors and muscarinic type 2 acetylcholine receptors in rats. J Am Coll Cardiol 2002; 39: 1866–1873
37. Chiale PA, Ferrari I: Autoantibodies in Chagas’ cardiomyopathy and arrhythmias. Autoimmunity 2001; 34: 205–210
38. Jahns R, Boivin V, Krapf T, Wallukat G, Boege F, Lohse MJ: Modulation of beta1-adrenoceptor activity by domain-specific antibodies and heart failure-associated autoantibodies. J Am Coll Cardiol 2000; 36: 1280–1287
39. Warraich RS, Dunn MJ, Yacoub MH: Subclass specificity of autoantibodies against myosin in patients with idiopathic dilated cardiomyopathy: pro-inflammatory antibodies in DCM patients. Biochem Biophys Res Commun 1999; 259: 255–261
40. Wallukat G, Wollenberger A, Morwinski R, Pitschner HF: Antib1-adrenoceptor autoantibodies with chronotropic activity from the serum of patients with dilated cardiomyopathy: mapping of epitopes in the first and second extracellular loops. J Mol Cell Cardiol 1995; 27: 397–406
41. Magnusson Y, Wallukat G, Waagstein F, Hjalmarson A ˚ , Hoebeke J: Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the b1-adrenoceptor with positive chronotropic effect. Circulation 1994; 89: 2760–2767
42. Krause EG, Bartel S, Beyerdorfer I, Wallukat G: Activation of cyclic AMP-dependent protein kinase in cardiomyocytes by antibeta 1-adrenoceptor autoantibodies from patients with idiopathic dilated cardiomyopathy. Blood Press Suppl 1996; 3: 37–40
43. Wallukat G, Reinke P, Dorffel WV, Luther HP, Bestvater K, Felix SB, Baumann G: Removal of autoantibodies in dilated cardiomyopathy by immunoadsorption. Int J Cardiol 1996; 54: 191–195
44. Wallukat G, Nissen E, Morwinski R, Muller J: Autoantibodies against the beta- and muscarinic receptors in cardiomyopathy. Herz 2000; 25: 261–266
45. Rose NR, Bona C: Defining criteria for autoimmune diseases (Witebsky’s postulates revisited). Immunol Today 1993; 14: 426– 430 46. Schwimmbeck PL, Badorff C, Rohn G, Schulze K, Schultheiss HP: The role of sensitized T-cells in myocarditis and dilated cardiomyopathy. Int J Cardiol 1996; 54: 117–125
47. Omerovic E, Bollano E, Andersson B, Kujacic V, Schulze W, Hjalmarson A, Waagstein F, Fu M: Induction of cardiomyopathy in severe combined immunodeficiency mice by transfer of lymphocytes from patients with idiopathic dilated cardiomyopathy. Autoimmunity 2000; 32: 271–280
48. Matsui S, Fu ML, Katsuda S, Hayase M, Yamaguchi N, Teraoka K, Kurihara T, Takekoshi N, Murakami E, Hoebeke J, Hjal
marson A ˚ : Peptides derived from cardiovascular G-proteincoupled receptors induce morphological cardiomyopathic changes in immunized rabbits. J Mol Cell Cardiol 1997; 29: 641– 655
49. Matsui S, Fu ML, Hayase M, Katsuda S, Yamaguchi N, Teraoka K, Kurihara T, Takekoshi N: Beneficial effect of muscarinic-2 antagonist on dilated cardiomyopathy induced by autoimmune mechanism against muscarinic-2 receptor. J Cardiovasc Pharmacol 2001; 38 Suppl 1: S43–49
50. Matsui S, Fu ML, Hayase M, Katsuda S, Yamaguchi N, Teraoka K, Kurihara T, Takekoshi N: Active immunization of combined beta1-adrenoceptor and M2-muscarinic receptor peptides induces cardiac hypertrophy in rabbits. J Card Fail 1999; 5: 246–254
51. Iwata M, Yoshikawa T, Baba A, Anzai T, Nakamura I, Wainai Y, Takahashi T, Ogawa S: Autoimmunity against the second extracellular loop of beta(1)-adrenergic receptors induces betaadrenergic receptor desensitization and myocardial hypertrophy in vivo. Circ Res 2001; 88: 578–586
52. Matsui S, Persson M, Fu HM, Hayase M, Katsuda S, Teraoka K, Kurihara T, Fu ML: Protective effect of bisoprolol on beta-1 adrenoceptor peptide-induced autoimmune myocardial damage in rabbits. Herz 2000; 25: 267–270
53. Dorffel WV, Felix SB, Wallukat G, Brehme S, Bestvater K, Hofmann T, Kleber FX, Baumann G, Reinke P: Short-term hemodynamic effects of immunoadsorption in dilated cardiomyopathy. Circulation 1997; 95: 1994–1997
54. Muller J, Wallukat G, Dandel M, Bieda H, Brandes K, Spiegelsberger S, Nissen E, Kunze R, Hetzer R: Immunoglobulin adsorption in patients with idiopathic dilated cardiomyopathy. Circulation 2000; 101: 385–391
55. Felix SB, Staudt A, Dorffel WV, Stangl V, Merkel K, Pohl M, Docke WD, Morgera S, Neumayer HH, Wernecke KD, et al: Hemodynamic effects of immunoadsorption and subsequent immunoglobulin substitution in dilated cardiomyopathy: threemonth results from a randomized study. J Am Coll Cardiol 2000; 35: 1590–1598
56. Staudt A, Schaper F, Stangl V, Plagemann A, Bohm M, Merkel K, Wallukat G, Wernecke KD, Stangl K, Baumann G, et al: Immunohistological changes in dilated cardiomyopathy induced by immunoadsorption therapy and subsequent immunoglobulin substitution. Circulation 2001; 103: 2681–2686
57. Christ T, Dobrev D, Wallukat G, Schuler S, Ravens U: Acute hemodynamic effects during immunoadsorption in patients with dilated cardiomyopathy positive for beta 1-adrenoceptor autoantibodies. Methods Find Exp Clin Pharmacol 2001; 23: 141– 144
58. Wallukat G, Fu HM, Matsui S, Hjalmarson A, Fu ML: Autoantibodies against M2 muscarinic receptors in patients with cardiomyopathy display non-desensitized agonist-like effects. Life Sci 1999; 64: 465–469
59. Felix SB, Staudt A, Landsberger M, Grosse Y, Stangl V, Spielhagen T, Wallukat G, Wernecke KD, Baumann G, Stangl K: Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption. J Am Coll Cardiol 2002; 39: 646–652

Text-only version of this page  |  Edit this page  |  Manage website  |  Website design: 2-minute-website.com