Skip to main content
SpringerLink
Log in

Platelets as target cells in rheumatoid arthritis and systemic lupus erythematosus: A platelet specific immunoglobulin inducing the release reaction

  • Originals
  • Published:
Rheumatology International Aims and scope Submit manuscript

Summary

Sera from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were assessed for in vitro platelet activation as measured by serotonin release; 24% (30) of 124 tested RA sera and 51% (35) of 69 SLE sera induced a significant 3H serotonin release. Investigation of 17 synovial fluid samples from RA patients revealed significant release in 82%. Concomitant testing for lymphocytotoxic antibodies and immune complexes did not show any correlation to platelet activation. Upon gel filtration the release-inducing activity of positive sera was localized in the region of 160 000 Daltons. Further characterization by ion exchange chromatography, immune electrophoresis, chromatographic and SDS PAGE molecular weight determinations, as well as analytical ultracentrifugation all confirmed the IgG nature of the release-inducing protein. Negative blocking experiments performed by preincubation of platelets with Fc-IgG fragments prior to challenge with a release-inducing serum excluded the participation of Fc receptors in the reaction. It was concluded that the release was caused by a platelet reactive IgG antibody. This antibody may also cause release of platelet mediators in vivo and may thus contribute to the pathogenesis of the generalized vasculopathy in both diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jørgensen L, Hovig T, Rowsell HC, Mustard JF (1970) Adenosine diphosphate-induced platelet aggregation and vascular injury in swine and rabbits. Am J Pathol 61:161–176

    Google Scholar 

  2. Harker LA, Slichter SJ (1972) Platelet and fibrinogen consumption in man. N Engl J Med 287:999–1005

    Google Scholar 

  3. Nachman RL, Polley M (1979) The platelet as an inflammatory cell. In: Weissman G (ed) Advances in inflammation research. Raven Press, New York, pp 169–173

    Google Scholar 

  4. Holmsen H, Day HJ, Stormorken H (1969) The blood platelet release reaction. Scand J Haematol (Suppl) 8:1–26

    Google Scholar 

  5. Weiss HJ (1975) Platelet physiology and abnormalities of platelet function. N Engl J Med 293:531–591

    Google Scholar 

  6. Nowoslawski A (1971) Immunological features of rheumatoid arthritis. In: Müller W, Harwerth HG., Fehr K (eds) Rheumatoid arthritis, pathogenetic mechanisms and consequences in therapeutics. Academic Press, London New York, pp 325–335

    Google Scholar 

  7. Conn DL, Schroeter AL, McDuffie FC (1976) Cutaneous vessel immune deposits in rheumatoid arthritis. Arthritis Rheum 19:15–20

    Google Scholar 

  8. Ullman S, Hoier-Madsen M, Halberg P, Jans H, Sylvest J (1979) Deposits of immunoglobulins and complement in skin of patients with rheumatoid arthritis. Scand J Rheumatol 8:119–123

    Google Scholar 

  9. Hutchinson RM, Davis P, Jayson MJV (1976) Thrombocytosis in rheumatoid arthritis. Am Rheum Dis 35:138–142

    Google Scholar 

  10. Valentini G, Chianese U, Tirri G, Giordano M (1978) Über Thrombozytose bei progredienter, generalisierter Sklerose (Sklerodermie) und bei anderen Rheumakrankheiten. Z Rheumatol 37:233–241

    Google Scholar 

  11. Smith AF, Castor CW (1978) Connective tissue activation. XII. Platelet abnormalities in patients with rheumatoid arthritis. J Rheumatol 5:177–183

    Google Scholar 

  12. Zeller J, Deicher H, Weissbarth E, Mielke H (1982) Serotonin contents of platelets in rheumatic diseases: Correlation to clinical activity. Arthritis Rheum (in press)

  13. Rabinowik Y, Dameshek W (1960) Systemic lupus erythematosus after “idiopathic” thombocytopenie purpura: a review. Ann Intern Med 52:1–28

    Google Scholar 

  14. Karpatkin S, Strick N, Karpatkin MB, Sishiud G (1972) Cumulative experience in the detection of antiplatelet antibody in 234 patients with ITP, SLE and other clinical disorders. Am J Med 52:776–785

    Google Scholar 

  15. Karpatkin S, Lackner HL (1975) Association of antiplatelet antibody with functional platelet disorders. Am J Med 59:599–604

    Google Scholar 

  16. Hedge UM, Gordon-Smith JC, Worlledge S (1977) Platelet antibodies in thrombocytopenic patients. Br J Haematol 35:113–122

    Google Scholar 

  17. Cines DB, Schreiber AD (1979) Immune thrombocytopenia. N Engl J Med 300:106–111

    Google Scholar 

  18. Weiss HJ, Rosove MH, Lages BA, Kaplan KL (1980) Acquired storage pool deficiency with increased platelet-associated IgG. Am J Med 69:711–717

    Google Scholar 

  19. Budman DR, Steinberg AD (1977) Haematologic aspects of systemic lupus erythematosus. Ann Intern Med 86:220–229

    Google Scholar 

  20. Cameron JS (1977) Platelets and glomerulonephritis. Nephron 18:253–258

    Google Scholar 

  21. Parbtani A, Cameron JS (1979) Platelet and plasma serotonin concentrations in glomerulonephritis I. Thromb Res 15:109–125

    Google Scholar 

  22. Clark WF, Lewis ML, Cameron JF, Parsons V (1975) Intrarenal platelet consumption in the diffuse proliferative nephritis of systemic lupus erythematosus. Clin Sci Mol Med 49:247–252

    Google Scholar 

  23. Fink PC, Piening U, Fricke M, Deicher H (1979) Platelet aggregation and aggregation inhibition by different antiglobulins and antiglobulin complexes from sera of patients with rheumatoid arthritis. Arthritis Rheum 22:896–903

    Google Scholar 

  24. Toshiro T (1977) Platelet aggregation in rheumatoid arthritis. Ryumachi 17:206–211

    Google Scholar 

  25. Ginsberg MH, O'Malley M (1977) Serum factors releasing serotonin from normal platelets: Relation of the manifestation of systemic lupus erythematosus. Ann Intern Med 87:564–567

    Google Scholar 

  26. Ropes MW, Bennett GA, Cobb S, Jocox RA, Jessar RA (1958) Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 9:175–176

    Google Scholar 

  27. Nydegger UE, Lambert PH, Gerber H, Miescher PA (1974) Circulating immune complexes in the serum in systemic lupus erythematosus and in carriers of hepatitis B antigen. J Clin Invest 54:297–309

    Google Scholar 

  28. Zubler RH, Lange G, Lambert PH, Miescher PA (1976) Detection of immune complexes in unheated sera by a modified 125J-Clq binding test. J Immunol 116:232–235

    Google Scholar 

  29. Waaler E (1940) On occurence of factor in immune serum activating specific agglutination of sheep blood corpuscles. Acta Pathol Microbiol Scand 17:172–188

    Google Scholar 

  30. Rose HM, Ragan C, Pearce E, Lipman MO (1948) Differential agglutination of normal and sensitized sheep erythrocytes by sera of patients with rheumatoid arthritis. Proc Soc Exp Biol 68:1–6

    Google Scholar 

  31. Ray IG, Scott RC (eds) (1972) Manual of tissue typing techniques. TJB, NJAD, NIH, Bethesda, Maryland, pp 50–55

    Google Scholar 

  32. Layne E (1957) Spectrophotometric and turbidimetric methods for measuring proteins. Methods Enzymol 3:447–453

    Google Scholar 

  33. Weber K, Osborn M (1969) The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem 244:4406–4412

    Google Scholar 

  34. Valone FH, Austen KF, Goetzel EJ (1979) Identification of the platelet activity in rheumatoid synovial fluid as an intermediate molecular weight complex of IgG. J Immunol 122:703–709

    Google Scholar 

  35. Karpatkin S, Siskind GW (1969) In vitro detection of platelet antibody in patients with idiopathic thrombocytopenic purpura and systemic lupus erythematosus. Blood 33: 795–812

    Google Scholar 

  36. Clancy R, Jenkins E, Firkin B (1972) Qualitative platelet abnormalities in idiopathic thrombocytopenic purpura. N Engl J Med 286:622–626

    Google Scholar 

  37. Dixon R, Rosse WF (1975) Annotation: Platelet antibody in autoimmune thrombocytopenia. Br J Haematol 31:129–134

    Google Scholar 

  38. Hirschman RJ, Shulman NR (1973) The use of platelet serotonin release as a sensitive method for detecting antiplatelet antibodies and a plasma antiplatelet factor in patients with idiopathic thrombocytopenic purpura. Br J Haematol 24:793–802

    Google Scholar 

  39. Heinrich D, Gutschank S, Mueller-Eckhardt C (1977) HLA-antibody-induced 14C-serotonin release from platelets. Vox Sang 33:65–78

    Google Scholar 

  40. Meyerhoff J, Dorsch CA (1981) Decrease platelet serotonin levels in systemic lupus erythematosus. Arthritis Rheum 24:1495–1500

    Google Scholar 

  41. Yeatts RP, Turner R, Collins R, Kaufmann J, Mashburn H (1978) Soluble and insoluble immune complex platelet interactions in rheumatoid inflammation. Ann Rheum Dis 37:421–427

    Google Scholar 

  42. Lüscher EF, Pfueller SL, Massini P (1973) Platelet aggregation by large molecules. Ser Haematol 3:382–391

    Google Scholar 

  43. Pfueller SL, Weber S, Lüscher EF (1977) Studies of the mechanism of the human platelet release reaction induced by immunologic stimuli. III. Relationship between the binding of soluble IgG aggregates to the Fc receptor and cell response in the presence and absence of plasma. J Immunol 118:514–524

    Google Scholar 

  44. Weissbarth E, Sedlacek HH, Seiler FR, Fricke M, Deicher H (1979) Release of 3H-serotonin and endogenous β-thromboglobulin from human platelets by immune complexes. Behring Inst Mitt 64:121–126

    Google Scholar 

  45. Shapleigh C, Valone FH, Schur PH, Goetzel EJ, Austen KF (1980) Platelet-activating activity in synovial fluids of patients with rheumatoid arthritis, juvenile rheumatoid arthritis, gont and noninflammatory arthropathies. Arthritis Rheum 23:800–807

    Google Scholar 

  46. Hay FC, Nineham LJ, Perumal R, Roitt JM (1979) Intra-articular and circulating immune complexes and antiglobulins (IgG and IgM) in rheumatoid arthritis: correlation with clinical features. Ann Rheum Dis 38:1–7

    Google Scholar 

  47. Kölsch E, Oberbarnscheidt J, Brüner K, Heuer J (1980) The Fc-receptor: Its role in the transmission of differentiation signals. Immunol Rev 49:61–78

    Google Scholar 

  48. Mencia-Huerta J, Benveniste J (1979) Platelet activating factor and macrophages. I. Evidence for the release from rat and mouse peritoneal macrophages and not from mastocytes. Eur J Immunol 9:405–415

    Google Scholar 

  49. Sánchez-Crespo M, Alfonso F, Egido J (1980) Platelet activating factor in anaphylaxis and phagocytosis. I. Release from human peripheral polymorphonuclears and monocytes during the stimulation by ionophore A23187 and phagocytosis but not from degranulating basophils. Immunology 40:645–655

    Google Scholar 

  50. Camussi G, Mencia-Huerta JM, Benveniste J (1977) Release of platelet activating factor and histamine. I. Effect of immune complexes, complement and neutrophils on human and rabbit mastocytes and basophils. Immunology 33:523–534

    Google Scholar 

  51. Cochrane CG (1971) Mechanisms involved in the deposition of immune complexes in tissues. J Exp Med 134:75s-89s

    Google Scholar 

  52. Kniker WT, Cochrane CG (1968) The location of circulating immune complexes in experimental serum sickness. The role of vasoactive amines and hydrodynamic forces. J Exp Med 127:119–135

    Google Scholar 

  53. Wiggins RC, Cochrane CG (1981) Current concepts in immunology: Immune complex-mediated biologic effects. N Engl J Med 304:518–520

    Google Scholar 

  54. Deicher H, Mielke H, Daniel W, Drommer W, Fischer M, Müller-Vahl H, Sybrecht G, Weissbarth E (1981) Studies on the vasculopathy of rheumatoid arthritis and its relation to “systemic rheumatoid disease”. In: Deicher H, Schulz LC (eds) Arthritis, models and mechanisms. Springer, Berlin Heidelberg New York, pp 118–134

    Google Scholar 

  55. Kijlstra A, Hilkema HA, Es LA van (1981) Conditions of vessel wall deposition of immune complexes in immunologically induced vascular diseases. In: Deicher H, Schulz LC (eds) Arthritis, models and mechanisms. Springer, Berlin Heidelberg New York, pp 106–117

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Abteilung Immunologie und Transfusionsmedizin, Zentrum Innere Medizin, Medizinische Hochschule Hannover, D-3000, Hannover, Federal Republic of Germany

    E. Weißbarth, B. Baruth, H. Mielke, W. Liman & H. Deicher

Authors
  1. E. Weißbarth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Baruth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Mielke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W. Liman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Deicher
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weißbarth, E., Baruth, B., Mielke, H. et al. Platelets as target cells in rheumatoid arthritis and systemic lupus erythematosus: A platelet specific immunoglobulin inducing the release reaction. Rheumatol Int 2, 67–73 (1982). https://doi.org/10.1007/BF00541248

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00541248

Key words

Search

Navigation