Titration of serum anti-ganglioside antibodies in patients with chronic medular injury previous to treatment with GM1 ganglioside

Titulação de anticorpos anti-gangliosídeos no soro de pacientes com lesão medular crônica e precedendo tratamento com gangliosídeo GM1

ORIGINAL ARTICLE

Titration of serum anti-ganglioside antibodies in patients with chronic medular injury previous to treatment with GM1 ganglioside

Titulação de anticorpos anti-gangliosídeos no soro de pacientes com lesão medular crônica e precedendo tratamento com gangliosídeo GM1

Tarcísio Eloy Pessoa Barros Filho^I; Ciro da Silva Filho^II

^IAssociate Professor

^IIFull Professor, Department of Histology and Embryology - Institute of Biomedical Science - USP - ICBUSP

^{Correspondence}

SUMMARY

Anti-ganglioside serum titers were evaluated by ELISA in 150 patients with complete spinal cord lesion for 6 to 12 months (IgG monosialo GM1, IgM monosialo GM1, IgG asialo GM1, IgM asialo GM1, IgG disialo GD1b e IgM disialo GD1b) prior to treatment with GM1 100 mg/day i.m. Only 4 patients showed positive titers for anti-asialo-GM1 (IgM) antibodies . All patients were clinically examined during and after treatment. No important side effects were observed with GM1 therapy. These results suggest that GM1-ganglioside administration in patients with chronic spinal cord injury is safe.

Key words: Gangliosides; Antibodies; Spinal cord injuries

RESUMO

Soro de 150 pacientes com lesão medular completa com 6 a 12 meses de duração foi analisado para titulação de anticorpos anti-gangliosídeos pelo método ELISA (IgG monosialo GM1, IgM monosialo GM1, IgG asialo GM1, IgM asialo GM1, IgG disialo GD1b e IgM disialo GD1b). Somente 4 pacientes apresentaram títulos elevados de anticorpos contra asialo GM1 (IgM). Os demais apresentaram níveis de anticorpos abaixo dos valores de referência e foram todos tratados com GM1 na dose de 100 mg por dia i.m. Todos os pacientes foram acompanhados clinicamente durante e após o tratamento com GM1. Não foram observados efeitos adversos importantes com a medicação. O tratamento de pacientes lesados medulares crônicos com o gangliosídeo GM1 mostrou-se seguro, nos pontos sem positividade sorológica para anticorpos anti-GM1 .

Descritores: Gangliosídeos; Anticorpos; Traumatismos da medula espinhal.

INTRODUCTION

Positive results were reported with the use of GM1 ganglioside in the treatment of patients with both acute and chronic medullar injury^(1,3,4,13). However, none of these studies described the anti-ganglioside antibody profile in the serums of the patients evaluated. The purpose of this study is to determine the anti-ganglioside antibody profile in patients with chronic rachiomedullar injury previous to treatment with GM1, and observe the occurrence of possible important side effects during and after the therapy with GM1.

MATERIAL AND METHODS

One hundred and fifty patients (120 men and 30 women) aged between 18 and 50 years were included in the study. All were diagnosed with complete medullar injury for 6 to 12 months. Prior to the 30-day treatment with GM1 ganglioside (100 mg/day i.m.) a blood sample was collected and submitted to the Mayo Clinic (USA) for titration of anti-ganglioside antibodies using the ELISA method.

The following reference values were adopted:

Monosialo-GM1 IgG: less than 1/500

Monosialo-GM1 IgM: less than 1/1000

Asialo-GM1 IgG: less than 1/4000

Asialo-GM1 IgM: less than 1/4000

Disialo-GD1b IgG: less than 1/1000

Disialo-GD1b IgM: less than 1/1000

During the therapy with GM1, patients with positive serology were monitored by periodical clinical evaluations, with a minimum one-year follow-up period.

RESULTS

Of the 150 patients evaluated, only 4 (3 men and 1 woman) presented anti-ganglioside antibody titers greater than the reference values, with positive serology for asialo-GM1 IgM (titer greater than 1/4000).

None of the 146 patients who received the medication presented any relevant side effect during or after the treatment cycle with GM1.

DISCUSSION

2.7% only of the patients who were analyzed in this study presented positive serology for anti-ganglioside antibodies (asialo-GM1) previous to treatment with GM1. None of the patients presented relevant side effects during or after the therapy with GM1.

Anti-ganglioside antibodies were reported in normal subjects without previous neurological condition or previous ganglioside treatment^{(2,6,7,10,12)}. Anti-ganglioside antibodies found in the serum of healthy subjects are generally of the IgM type^(8,9). The titration of anti-GM1 (IgM) antibodies in 24 patients with chronic medullar injury who were not treated with GM1 showed significantly higher mean values as compared to the control group of 26 healthy subjects⁽⁵⁾.

The healthy subjects received i.m. injections of 100 mg/day gangliosides for 15 days⁽²⁾. Of the 12 subjects injected, 7 presented no ganglioside-responsive antibodies, before and during the treatment. In the remaining 5 subjects, anti-ganglioside antibodies were present before the treatment and persisted during its course. A slight increase in the antibody titer was observed in one patient during the treatment. In the same study, several cytokines, including IL1 alpha, TNF-alpha, INF-gamma, IL-2 and sIL2R cytokines, were evaluated in the serum of the treated patients. No increase was observed in the level of these cytokines. These results indicate that, other than the specific antibody patterns, other important mediators of the immune system were not affected by the treatment with gangliosides.

Anti-ganglioside antibody levels were monitored in 12 patients with Alzheimer's disease who received daily doses of 100 mg gangliosides during a 90-day period⁽¹²⁾. Ten patients presented anti-ganglioside antibodies before the beginning of the treatment. The most frequently detected ganglioside was LM1. These antibody titers oscillated during the ganglioside administration period, although they were reduced at the end of the study. In another study, anti-GM1 antibodies were evaluated in 418 samples of individuals receiving parenteral gangliosides⁽¹⁴⁾. No association between the treatment and antibody levels was reported.

Anti-GM1 antibody levels were monitored in 60 patients with Chaga's disease, both before and during the treatment with gangliosides for a 12-month period⁽⁶⁾. None of the patients presented positive titers for anti-GM1 antibodies in the baseline, and no significant change was observed in those titers following the treatment with gangliosides.

Anti-GM1 antibodies were evaluated in 10 patients with Parkinson's disease before and after an 18-week treatment with one i.v. bolus dose of 1000 mg GM1 ganglioside followed by daily doses of 200 mg s.c. None of the patients presented higher anti-GM1 antibody titers at the end of the treatment⁽¹¹⁾.

In conclusion, the treatment of patients with chronic medullar injuries with GM1 ganglioside showed to be safe in patients without positive serology for anti-GM1 antibodies previous to the therapy.

Work performed at the Departamento de Ortopedia e Traumatologia da Faculdade de Medicina da Universidade de São Paulo - São Paulo - SP

Trabalho recebido em 24/01/2003

Aprovado em 20/03/2003

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Correspondence to

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Publication Dates

• Publication in this collection
  03 June 2003
• Date of issue
  Apr 2003

History

• Received
  24 Jan 2003
• Accepted
  20 Mar 2003