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Acta Neuropathologica

, Volume 68, Issue 1, pp 39–47 | Cite as

Immunocytochemical studies of serum proteins and immunoglobulins in human sural nerve biopsies

  • U. G. Liebert
  • R. J. Seitz
  • T. Weber
  • W. Wechsler
Original Works

Summary

Post-embedding immunocytochemical studies on immunoglobulins (Ig) and other serum proteins were carried out on 38 human sural nerve biopsies using the PAP method. In addition to toxic, hereditary, metabolic, dysproteinemic, and vasculiticneuritic neuropathies, morphologically normal sural nerves were included as controls. The intensity of the immunocytochemical reactions was strong for proteins, such as IgG, the light chains of Igs, and albumin, but weak or absent for others like complement component C3, IgA, ceruloplasmin, and alpha-1-antitrypsin (AAT) in normal nerve biopsies and in all pathologic groups. IgG, the light chains of immunoglobulins, and albumin could readily be detected in perineurium, endoneurial interstitium, and blood vessel walls. IgM, C3, and beta-lipoprotein (BLP) were largely confined to the walls of blood vessels and perineurium, thus indicating that they do not penetrate the blood nerve barrier. Only in a few cases, in vasculitic-neuritic and dysproteinemic neuropathies, staining of the endoneurial intersitium for IgM and C3 was observed. Increased staining for the corresponding heavy or light chains was not detected in the endoneurium in any of the neuropathies associated with gammopathy.

The results stress that PAP immunocytochemistry is suitable for studying the blood-nerve barrier (BNB) and provides new aspects to the concept of the BNB with respect to the steady state of serum proteins between endoneurial and vascular spaces. It is suggested that, in addition to serum concentration and molecular weight of serum proteins, the permeability of the BNB is influenced by other yet undefined factors.

Key words

PAP immunocytochemistry Immunoglobulin Serum proteins Sural nerve biopsies Blood-nerve barrier (BNB) 

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References

  1. Abrams GM, Latov N, Hays AP, Sherman W, Zimmerman EA (1982) Immunocytochemical studies of human peripheral nerve with serum from patients with polyneuropathy and paraproteinemia. Neurology 32:821–826Google Scholar
  2. Bosman FT, Nieuwenhuijzen-Kruseman AC (1977) Clinical applications of the enzyme-labelled antibody method. J Histochem Cytochem 27:1140–1147Google Scholar
  3. Burns J (1978) Immunohistological methods and their application in the routine laboratory. In: Anthony PP, Woolf N (eds) Recent advances in histopathology, no 10. Churchill Livingstone, Edinburgh London New York, pp 337–350Google Scholar
  4. Chazot G, Berger B, Carrier H (1976) Manifestation neurologiques des gammapathies monoclonales. Rev Neurol (Paris) 132:195–212Google Scholar
  5. Dalakas MC, Engel WK (1980) Immunoglobulin and complement deposits in nerves of patients with chronic relapsing polyneuropathy. Arch Neurol 37:637–640Google Scholar
  6. Dalakas MC, Engel WK (1981) Polyneuropathy with monoclonal gammopathy: Studies of 11 patients. Ann Neurol 10:45–52Google Scholar
  7. Felgenhauer K, Schliep S, Rapiel N (1976) Evaluation of the blood-CSF barrier by protein gradients and the humoral immune response within the central nervous system. J Neurol Sci 30:113–128Google Scholar
  8. Felgenhauer K (1980) Protein filtration and secretion at human body fluid barriers. Pflügers Arch 384:9–17Google Scholar
  9. Heininger K, Liebert UG, Toykak V (1984) Chronic inflammatory polyneuropathy: Reduction of nerve conduction velocities in monkeys by systemic passive transfer of immunoglobulin G. J Neurol Sci 66:1–14Google Scholar
  10. Hsu SM, Raine L, Fanger H (1981) A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol 75:734–738Google Scholar
  11. Iwashita H, Argyrakis A, Lowitzsch K, Spaar FF (1974) Polyneuropathy in Waldenström's macroglobinemia. J Neurol Sci 21:341–354Google Scholar
  12. Liebert UG, Schwendemann G, Heininger K (1983) Immunocytochemical demonstration of immunoglobulins in the peripheral nerves after systemic passive transfer to mice and monkeys. Acta Neurol Scand 68:185 [Abstr]Google Scholar
  13. Low PA, Yao JK, Poduslo JF, Donald DE, Dyck PJ (1982) Peripheral nerve microenvironment: Collection of endoneurially enriched fluid. Exp Neurol 77:208–214Google Scholar
  14. Luijten JAFM, de la Faille-Kuyper EHB (1972) The occurrence of IgM and complement factors along myelin sheaths of peripheral nerves. J Neurol Sci 15:219–224Google Scholar
  15. Meier C, Vandevelde M, Steck A, Zurbriggen A (1983) Demyelinating neuropathy associated with monoclonal IgM-paraproteinaemia. J Neurol Sci 63:353–367Google Scholar
  16. Mepham BL, Frater W, Mitchell BS (1979) The use of proteolytic enzymes to improve immunoglobulin staining by the peroxidase-antiperoxidase technique. Histochem J 11:345–357Google Scholar
  17. de la Motte DJ, Hall SM, Allt G (1975) A study of the perineurium in peripheral nerve pathology. Acta Neuropathol (Berl) 33:257–270Google Scholar
  18. Myers RR, Heckman PM, Powell HC (1983) Endoneurial fluid is hypertonic. J Neuropathol Exp Neurol 42:217–224Google Scholar
  19. Olsson Y (1971) Studies on vascular permeability in peripheral nerves. IV. Distribution of intravenously injected protein tracers in the peripheral nervous system of various species. Acta Neuropathol (Berl) 17:114–126Google Scholar
  20. Olsson Y (1975) Vascular permeability in the peripheral nervous system. In: Dyck PJ, Thomas PK, Lambert EH (eds) Peripheral neuropathy, vol 1. Sauders, Philadelphia, pp 190–200Google Scholar
  21. Propp RP, Means E, Deibel R, Dherer G, Barron K (1975) Waldenström's macroglobulinemia and neuropathy. Neurology 25:980–988Google Scholar
  22. Seitz RJ, Heininger K, Schwendemann G (1985) The mouse blood brain barrier and blood nerve barrier for IgG: a tracer study by use of the avidin-biotin system. Acta Neuropathol (Berl) (in press)Google Scholar
  23. Seitz RJ, Weber T, Wechsler W (1983) Immunzytochemische Untersuchungen von Immunglobulinen, Komplement (C3) und Albumin an Muskelbiopsien, Fortschritte der Myologie, Bd VII, pp 165–172Google Scholar
  24. Shinowara NL, Michel ME, Rapoport SI (1982) Morphological correlates of permeability in the frog perineurium: Vesicles and “transcellular channels”. Cell Tissue Res 227:11–22Google Scholar
  25. Smith IS, Kahn SN, Lacey BW, King RHM, Eames RA, Whybrew DJ, Thomas PK (1983) Chronic demyelinating neuropathy associated with benign IgM paraproteinemia. Brain 106:169–195Google Scholar
  26. Söderfeldt B, Olsson Y, Kristensson K (1973) The perineurium as a diffusion barrier to protein traces in human peripheral nerve. Acta Neuropathol (Berl) 25:120–126Google Scholar
  27. Stefasson K, Marton L, Antel JP, Wollmann RL, Roos RP, Cheijfec G, Arnason BGW (1983) Neuropathy accompanying IgM-lambda monoclonal gammopathy. Acta Neuropathol (Berl) 59:255–261Google Scholar
  28. Sternberger LA (1979) Immunocytochemistry, chap 5, Unlabeled antibody peroxidase-antiperoxidase (PAP) method, 2nd edn. Wiley, New York, pp 104–169Google Scholar
  29. Swash M, Perrin J, Schwartz MS (1979) Significance of immunoglobulin deposition in peripheral nerve in neuropathies associated with paraproteinemia. J Neurol Neurosurg Psychiatry 42:179–183Google Scholar
  30. Van Lis JMJ, Jennekens FGI (1977) Plasma proteins in human peripheral nerve. J Neurol Sci 34:329–341Google Scholar
  31. Weston PD, Poole AR (1973) Antibodies to enzymes and their use. In: Dingle JT (ed) Lysosomes in biology and pathology, vol 3, chapt 16. Front Biol, Vol 29. North-Holland, Amsterdam, pp 425–464Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • U. G. Liebert
    • 1
  • R. J. Seitz
    • 1
  • T. Weber
    • 1
  • W. Wechsler
    • 1
  1. 1.Institute of NeuropathologyUniversity of DüsseldorfDüsseldorfFederal Republic of Germany

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