Skip to main content
Log in

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

  • Original Works
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

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.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • 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 32:821–826

    Google Scholar 

  • Bosman FT, Nieuwenhuijzen-Kruseman AC (1977) Clinical applications of the enzyme-labelled antibody method. J Histochem Cytochem 27:1140–1147

    Google Scholar 

  • 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 337–350

    Google Scholar 

  • Chazot G, Berger B, Carrier H (1976) Manifestation neurologiques des gammapathies monoclonales. Rev Neurol (Paris) 132:195–212

    Google Scholar 

  • Dalakas MC, Engel WK (1980) Immunoglobulin and complement deposits in nerves of patients with chronic relapsing polyneuropathy. Arch Neurol 37:637–640

    Google Scholar 

  • Dalakas MC, Engel WK (1981) Polyneuropathy with monoclonal gammopathy: Studies of 11 patients. Ann Neurol 10:45–52

    Google Scholar 

  • 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 30:113–128

    Google Scholar 

  • Felgenhauer K (1980) Protein filtration and secretion at human body fluid barriers. Pflügers Arch 384:9–17

    Google Scholar 

  • 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 66:1–14

    Google Scholar 

  • 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 75:734–738

    Google Scholar 

  • Iwashita H, Argyrakis A, Lowitzsch K, Spaar FF (1974) Polyneuropathy in Waldenström's macroglobinemia. J Neurol Sci 21:341–354

    Google Scholar 

  • 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 

  • Low PA, Yao JK, Poduslo JF, Donald DE, Dyck PJ (1982) Peripheral nerve microenvironment: Collection of endoneurially enriched fluid. Exp Neurol 77:208–214

    Google Scholar 

  • Luijten JAFM, de la Faille-Kuyper EHB (1972) The occurrence of IgM and complement factors along myelin sheaths of peripheral nerves. J Neurol Sci 15:219–224

    Google Scholar 

  • Meier C, Vandevelde M, Steck A, Zurbriggen A (1983) Demyelinating neuropathy associated with monoclonal IgM-paraproteinaemia. J Neurol Sci 63:353–367

    Google Scholar 

  • Mepham BL, Frater W, Mitchell BS (1979) The use of proteolytic enzymes to improve immunoglobulin staining by the peroxidase-antiperoxidase technique. Histochem J 11:345–357

    Google Scholar 

  • de la Motte DJ, Hall SM, Allt G (1975) A study of the perineurium in peripheral nerve pathology. Acta Neuropathol (Berl) 33:257–270

    Google Scholar 

  • Myers RR, Heckman PM, Powell HC (1983) Endoneurial fluid is hypertonic. J Neuropathol Exp Neurol 42:217–224

    Google Scholar 

  • 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) 17:114–126

    Google Scholar 

  • 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 190–200

    Google Scholar 

  • Propp RP, Means E, Deibel R, Dherer G, Barron K (1975) Waldenström's macroglobulinemia and neuropathy. Neurology 25:980–988

    Google Scholar 

  • 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)

  • Seitz RJ, Weber T, Wechsler W (1983) Immunzytochemische Untersuchungen von Immunglobulinen, Komplement (C3) und Albumin an Muskelbiopsien, Fortschritte der Myologie, Bd VII, pp 165–172

    Google Scholar 

  • Shinowara NL, Michel ME, Rapoport SI (1982) Morphological correlates of permeability in the frog perineurium: Vesicles and “transcellular channels”. Cell Tissue Res 227:11–22

    Google Scholar 

  • Smith IS, Kahn SN, Lacey BW, King RHM, Eames RA, Whybrew DJ, Thomas PK (1983) Chronic demyelinating neuropathy associated with benign IgM paraproteinemia. Brain 106:169–195

    Google Scholar 

  • Söderfeldt B, Olsson Y, Kristensson K (1973) The perineurium as a diffusion barrier to protein traces in human peripheral nerve. Acta Neuropathol (Berl) 25:120–126

    Google Scholar 

  • Stefasson K, Marton L, Antel JP, Wollmann RL, Roos RP, Cheijfec G, Arnason BGW (1983) Neuropathy accompanying IgM-lambda monoclonal gammopathy. Acta Neuropathol (Berl) 59:255–261

    Google Scholar 

  • Sternberger LA (1979) Immunocytochemistry, chap 5, Unlabeled antibody peroxidase-antiperoxidase (PAP) method, 2nd edn. Wiley, New York, pp 104–169

    Google Scholar 

  • Swash M, Perrin J, Schwartz MS (1979) Significance of immunoglobulin deposition in peripheral nerve in neuropathies associated with paraproteinemia. J Neurol Neurosurg Psychiatry 42:179–183

    Google Scholar 

  • Van Lis JMJ, Jennekens FGI (1977) Plasma proteins in human peripheral nerve. J Neurol Sci 34:329–341

    Google Scholar 

  • 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 425–464

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liebert, U.G., Seitz, R.J., Weber, T. et al. Immunocytochemical studies of serum proteins and immunoglobulins in human sural nerve biopsies. Acta Neuropathol 68, 39–47 (1985). https://doi.org/10.1007/BF00688954

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00688954

Key words

Navigation