Expression of HLA-DR in pheripheral nerve of amyotrophic lateral sclerosis

Oliveira, A.S.B.; Isozaki, E.; Younger, D.; Gabbai, A.A.; Hays, A.P.

doi:10.1590/S0004-282X1994000400007

Abstracts

To investigate the possibility of local antigen presentation within the peripheral nerve in amyotrophic lateral sclerosis (ALS), cryostat sections of 83 peripheral nerve biopsies were stained for the demonstration of HLA-DR using a monoclonal antibody. Forty samples showed increased expression of HLA-DR in endoneurium. The phenotypic characteristics of the HLA-DR positive cells are chiefly Schwann cells, using S-100 protein as a marker. We did not detect any co-expression between HLA-DR and NF (axons) and HLA-DR and myelin marker. We also detected co-expression between HLA-DR and NGFr in a majority of HLA-DR positive cells. Inflammatory cells were infrequent, being detected only in 11 cases, predominantly around epineurial blood vessels. Motor and sensory nerve biopsies performed simultaneously showed higher expression of HLA-DR in motor nerves in 2 out of 4 patients. The significance of these findings is not clear. The presence of endoneurial cells expressing HLA-DR suggests that an autoimmune mechanism may be involved in ALS having Schwann as the main target.

amyotrophic lateral sclerosis; peripheral nerve; histocompatibity antigen

Para investigar a possibilidade de comprometimento auto imune no nervo periférico de pacientes com esclerose lateral amiotrófica (ELA) 83 biópsias do nervo periférico de 79 pacientes (51 sexo masculino, 28 sexo feminino) com média de idade de 62 anos (variação de 19 a 82) foram congeladas e coradas para demonstração de HLA-DR usando anticorpo monoclonal. Quarenta amostras (48%) mostraram expressão nitidamente aumentada de HLA-DR na região endoneural. Usando proteína S-100 como marcador, demonstramos que HLA-DR se expressava principalmente nas células de Schwann. Não encontramos co-expressão com HLA-DR usando anticorpos antineurofilamento ou antimielina, mas detectamos co-expressão de HLA-DR e anti-receptor de fator de crescimento nervoso na maioria das células HLA-DR positivas. Células inflamatórias foram encontradas ocasionalmente, sendo detectadas em somente 11 casos, predominantemente ao redor de vasos sanguíneos epineurais. Biópsias de nervo sensitivo e motor feitas simultaneamente mostraram maior expressão de HLA-DR em nervos motores de 2 dos 4 pacientes. A significância desses achados ainda não é clara. A presença de células endoneurais expressando HLA-DR sugere que mecanismos auto imunes podem estar envolvidos na ELA tendo a célula de Schwann como um dos principais alvos.

esclerose lateral amiotrófica; nervo periférico; antígeno de histocompatibilidade

Expression of HLA-DR in pheripheral nerve of amyotrophic lateral sclerosis

Expressão de HLA-DR em nervo periférico de esclerose lateral amiotrófica

A.S.B. Oliveira^I; E. Isozaki^II; D. Younger^II; A.A. Gabbai^I; A.P. Hays^II

^IDisciplina de Neurologia da Escola Paulista de Medicina

^IIDivision of Neuropathology, College of Physicians and Surgeons, Columbia University, New York, NY

SUMMARY

To investigate the possibility of local antigen presentation within the peripheral nerve in amyotrophic lateral sclerosis (ALS), cryostat sections of 83 peripheral nerve biopsies were stained for the demonstration of HLA-DR using a monoclonal antibody. Forty samples showed increased expression of HLA-DR in endoneurium. The phenotypic characteristics of the HLA-DR positive cells are chiefly Schwann cells, using S-100 protein as a marker. We did not detect any co-expression between HLA-DR and NF (axons) and HLA-DR and myelin marker. We also detected co-expression between HLA-DR and NGFr in a majority of HLA-DR positive cells. Inflammatory cells were infrequent, being detected only in 11 cases, predominantly around epineurial blood vessels. Motor and sensory nerve biopsies performed simultaneously showed higher expression of HLA-DR in motor nerves in 2 out of 4 patients. The significance of these findings is not clear. The presence of endoneurial cells expressing HLA-DR suggests that an autoimmune mechanism may be involved in ALS having Schwann as the main target.

Key words: amyotrophic lateral sclerosis, peripheral nerve, histocompatibity antigen.

RESUMO

Para investigar a possibilidade de comprometimento auto imune no nervo periférico de pacientes com esclerose lateral amiotrófica (ELA) 83 biópsias do nervo periférico de 79 pacientes (51 sexo masculino, 28 sexo feminino) com média de idade de 62 anos (variação de 19 a 82) foram congeladas e coradas para demonstração de HLA-DR usando anticorpo monoclonal. Quarenta amostras (48%) mostraram expressão nitidamente aumentada de HLA-DR na região endoneural. Usando proteína S-100 como marcador, demonstramos que HLA-DR se expressava principalmente nas células de Schwann. Não encontramos co-expressão com HLA-DR usando anticorpos antineurofilamento ou antimielina, mas detectamos co-expressão de HLA-DR e anti-receptor de fator de crescimento nervoso na maioria das células HLA-DR positivas. Células inflamatórias foram encontradas ocasionalmente, sendo detectadas em somente 11 casos, predominantemente ao redor de vasos sanguíneos epineurais. Biópsias de nervo sensitivo e motor feitas simultaneamente mostraram maior expressão de HLA-DR em nervos motores de 2 dos 4 pacientes. A significância desses achados ainda não é clara. A presença de células endoneurais expressando HLA-DR sugere que mecanismos auto imunes podem estar envolvidos na ELA tendo a célula de Schwann como um dos principais alvos.

Palavras-chave: esclerose lateral amiotrófica, nervo periférico, antígeno de histocompatibilidade.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Aceite: 12-abril-1994.

Dr. Aracy Oliveira was supported by postodoctoral fellowship from the Brazilian Research Council (CNPq).

Dr. Acary S.B. Oliveira - Disciplina de Neurologia, Escola Paulista de Medicina - Rua Botucatu 740 - 04023-900 São Paulo SP - Brasil.

1. Allison J, Campbell IL, Morahan G, Mandell TE, Harrison LC, Miller JFAP. Diabetes in transgenic mice resulting from over-expression of class I histocompatibility molecules in pancreatic beta cells. Nature 1988, 339:529-533.
2. Appel SH, Smith RG, Engelhardt JI, Stefani E. Evidence for autoimmunity in amyotrophic lateral sclerosis. J Neurol Sci 1993, 118:169-174.
3. Bradley SG, Good P, Rasool CG, Adelman LS. Morphometric and histochemical studies of peripheral nerves in amyotrophic lateral sclerosis. Ann Neurol 1983, 14:267-277.
4. Dalchan R, Kirkley J, Fabre JW. Monoclonal antibody to a human leukocyte specific membrane glycoprotein probably homologous to the leucocyte common (L-C) antigens of the rat. Eur J Immunol 1980, 10:737-744.
5. Hanyu N, Oguchi K, Yanagisawa N, Tsukagoshi H. Degeneration and regeneration of ventral root motor fibers in amyotrophic lateral sclerosis: morphometric studies of cervical ventral roots. J Neurol Sci 1982, 55:99-115.
6. Julien R, Ferrer X. Multiple sclerosis an overview. Biom Pharmacother 1989, 43:335-346.
7. Kawamata T, Akiyama H, Yamada T, McGeer PL. immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am J Pathol 1992, 140:691-707.
8. Lampson LA, Kushner PD, Sobel RA. Major histocompatibility complex antigen expression in the affected tissues in amyotrophic lateral sclerosis. Ann Neurol 1990, 28:365-372.
9. Matis L, Glimcher L, Paul W, Schwartz R. Magnitude of responses of histocompatibility-restricted T-cell clones is a function of the product of the concentrations of antigen and la molecules. Proc Natl Acad Sci USA 1983, 80:6019-6022.
10. Mazzuca M, Lhermitte M, Lafitte, Poussel P. Use of lectins for detection of glycoconjugates in the glandular cells of the human bronchia mucosa. Histochem Cytochem 1982, 30:956-966.
11. Pollard JD, McCombe PA, Baverstock J, Gatenby PA, Mc Leod JG. Class II antigen expression and T lymphocyte subsets in chronic inflammatory demyelinating polyneuropathy. J Neuroimmunol 1986, 13:123-134.
12. Scarpini E, Lisak RP, Beretta S, Velicogna M, Doronzo R, Moggio M, Jann S, Scarlato G. Quantitative assesment of class II molecules in normal and pathological nerves. Brain 1990, 113:659-675.
13. Schroder HD, Olsson T, Solders G, Kristensson K, Link H. HLA-DR expressing cells and T-lymphocytes in sural nerve biopsies. Muscle & Nerve 1988, 11:864-870.
14. Shy ME. Immunological aspects of motor neuron disease. Res Publ Assoc Res Nerv Ment Dis 1991, 68:241-256.
15. Snider WD, Johnson EM. Neurotrophic molecules. Ann Neurol 1989, 26:489-506.
16. Tandan R, Bradley WG. Amyotrophic lateral sclerosis:part 2. Etiopathogenesis. Ann Neurol 1985, 18:419-431.
17. Taniuchi M, Clark HB, Johnson EM. Induction of nerve growth factor receptor in Schwann cells after axotomy. Proc Natl Acad Sci USA 1986, 83:4094-4098.
18. Traugott U, Raine CS. Evidence for antigen presentation in situ by endothelial cells and astrocytes. J Neurol Sci 1985, 69:365-370.
19. Troost D, Van Den Oord J J, De Jong JMBV. Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 1990, 16:401-410.
20. Urban ND, Zier KS. Negative signal transmission through class II molecules on activated T cells. Hum Immunol 1991, 31:170-179.
21. Younger DS, Rowland LP, Latov N et al. Motor neuron disease and amyotrophic lateral sclerosis: relation of high CSF protein content to paraproteinemia and clinical syndromes. Neurology 1990, 40:595-599.

Publication Dates

Publication in this collection
19 Jan 2011
Date of issue
Dec 1994

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Allison J, Campbell IL, Morahan G, Mandell TE, Harrison LC, Miller JFAP. Diabetes in transgenic mice resulting from over-expression of class I histocompatibility molecules in pancreatic beta cells. Nature 1988, 339:529-533.

[2] 2. Appel SH, Smith RG, Engelhardt JI, Stefani E. Evidence for autoimmunity in amyotrophic lateral sclerosis. J Neurol Sci 1993, 118:169-174.

[3] 3. Bradley SG, Good P, Rasool CG, Adelman LS. Morphometric and histochemical studies of peripheral nerves in amyotrophic lateral sclerosis. Ann Neurol 1983, 14:267-277.

[4] 4. Dalchan R, Kirkley J, Fabre JW. Monoclonal antibody to a human leukocyte specific membrane glycoprotein probably homologous to the leucocyte common (L-C) antigens of the rat. Eur J Immunol 1980, 10:737-744.

[5] 5. Hanyu N, Oguchi K, Yanagisawa N, Tsukagoshi H. Degeneration and regeneration of ventral root motor fibers in amyotrophic lateral sclerosis: morphometric studies of cervical ventral roots. J Neurol Sci 1982, 55:99-115.

[6] 6. Julien R, Ferrer X. Multiple sclerosis an overview. Biom Pharmacother 1989, 43:335-346.

[7] 7. Kawamata T, Akiyama H, Yamada T, McGeer PL. immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am J Pathol 1992, 140:691-707.

[8] 8. Lampson LA, Kushner PD, Sobel RA. Major histocompatibility complex antigen expression in the affected tissues in amyotrophic lateral sclerosis. Ann Neurol 1990, 28:365-372.

[9] 9. Matis L, Glimcher L, Paul W, Schwartz R. Magnitude of responses of histocompatibility-restricted T-cell clones is a function of the product of the concentrations of antigen and la molecules. Proc Natl Acad Sci USA 1983, 80:6019-6022.

[10] 10. Mazzuca M, Lhermitte M, Lafitte, Poussel P. Use of lectins for detection of glycoconjugates in the glandular cells of the human bronchia mucosa. Histochem Cytochem 1982, 30:956-966.

[11] 11. Pollard JD, McCombe PA, Baverstock J, Gatenby PA, Mc Leod JG. Class II antigen expression and T lymphocyte subsets in chronic inflammatory demyelinating polyneuropathy. J Neuroimmunol 1986, 13:123-134.

[12] 12. Scarpini E, Lisak RP, Beretta S, Velicogna M, Doronzo R, Moggio M, Jann S, Scarlato G. Quantitative assesment of class II molecules in normal and pathological nerves. Brain 1990, 113:659-675.

[13] 13. Schroder HD, Olsson T, Solders G, Kristensson K, Link H. HLA-DR expressing cells and T-lymphocytes in sural nerve biopsies. Muscle & Nerve 1988, 11:864-870.

[14] 14. Shy ME. Immunological aspects of motor neuron disease. Res Publ Assoc Res Nerv Ment Dis 1991, 68:241-256.

[15] 15. Snider WD, Johnson EM. Neurotrophic molecules. Ann Neurol 1989, 26:489-506.

[16] 16. Tandan R, Bradley WG. Amyotrophic lateral sclerosis:part 2. Etiopathogenesis. Ann Neurol 1985, 18:419-431.

[17] 17. Taniuchi M, Clark HB, Johnson EM. Induction of nerve growth factor receptor in Schwann cells after axotomy. Proc Natl Acad Sci USA 1986, 83:4094-4098.

[18] 18. Traugott U, Raine CS. Evidence for antigen presentation in situ by endothelial cells and astrocytes. J Neurol Sci 1985, 69:365-370.

[19] 19. Troost D, Van Den Oord J J, De Jong JMBV. Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 1990, 16:401-410.

[20] 20. Urban ND, Zier KS. Negative signal transmission through class II molecules on activated T cells. Hum Immunol 1991, 31:170-179.

[21] 21. Younger DS, Rowland LP, Latov N et al. Motor neuron disease and amyotrophic lateral sclerosis: relation of high CSF protein content to paraproteinemia and clinical syndromes. Neurology 1990, 40:595-599.