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Polyneuropathy associated with monoclonal gammopathy: A clinical, neurophysiological and immunological study
Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
1994 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis is based upon clinical, neurophysiological, and immunological studies of polyneuropathy (symmetrical impairment of sensory and motor nerve function) in patients with monoclonal gammopathies, that is, patients characterized by proliferation of a plasma-cell clone secreting homogeneous immWloglobulins (M-component), which in some patients has serum antibody reactivity against peripheral nerve myelin.

The prevalence of clinical polyneuropathy in patients with monoclonal gammopathy (n=3) was 36%, and the prevalence of all forms of polyneuropathy including patients with neurophysiological signs only andpatients with probable polyneuropathy (signs but no symptoms) was 58%. IgM isotype of the M-component was associated with a high risk of clinical polyneuropathy (5 of 6; 83%). 3 patients, all with a demyelinating polyneuropathy, had antibodies against peripheral nerve myelin. It is concluded that polyneuropathy is common in patients with monoclonal gammopathy, but that only some polyneuropathies are of the demyelinating type and associated with circulating antibodies against peripheral nerve myelin.

Immunofixation was superior to plasma agarose electrophoresis in detecting M-components in patients investigated for polyneuropathy (n=83). The prevalence of M-components was 7% (3 of 42 patients without obvious associated disease). The prevalence of M-components in the subgroup of patients with demyelinating polyneuropathy was even higher (21 %). Hence, patients with polyneuropathy should be screened for Mcomponents by a sensitive technique, not only to reveal a possible pathogenetie factor, but also because of the possibility of successful immunosuppressive treatment in some of them.

Antibodies against peripheral nerve myelin were also shown to occur in healthy blood donors (25 of255; 10%). Only 2 of them had clinical and neurophysiological evidence of mild polyneuropathy. Their antibodies were shown to react with several proteins in peripheral nerve myelin, in contrast to patients with monoclonal gammopathy and polyneuropathy whose antibodies reacted with low molecular weight glycoproteins (14-30 kDa) in peripheral nerve myelin. The study confirms previous findings of autoantibodies in healthy persons.

A positive correlation emerged between the amount of antibodies against peripheral nerve myelin and the proportion of circulating B-1 lymphocytes, known to be responsible for autoantibody production, in patients with polyneuropathy associated with monoclonal gammopathy. The findings suggest that B-1 cells produce antimyelin antibodies and support the idea of an autoinunune mechanism for the pathogenesis of polyneuropathy in some patients.

Soluble interleukin-2 receptor (siL-2R) is secreted by activated T cells, and was elevated in 7 of 19 patients with monoclonal gammopathy and demyelinating polyneuropathy, as compared to 2 of 19 patients withmonoclonal ganuuopathy without polyneuropathy and in 1 of 15 healthy controls. The finding supports the hypothesis that T cells may have a regulatory role in the M-component production.

Genomic typing for human leukocyte antigen (HLA) -DR and -DQ genes was done in 55 patients with monoclonal gammopathy. A polyneuropathy of demyelinating type was established in26 patients. Among these people an association was found with the presence of a tryptophan amino acid residue at position 9 of the DRB chain. This position is part of the first hypervariable region of the DRB chain, and may be of importance in detennining preferential peptide-binding capacity of the HLA-DR molecule. Anti-myelin-associated glycoprotein (MAG) antibodies were fmmd in 15 of 17 patients with an IgM M-component and demyelinating polyneuropathy (14 of these 15 people carried a tryptophan at position 9), supporting the pathogenctic role of an autoimmune response against MAG. The finding of an HLA class II association may indicate a pathogenic role ofT cell immunity in this condition.

3 of 5 patients with monoclonal IgM and antibodies against peripheral nerve myelin responded to immunosuppressive treatment. In 3 patients the clinical response and the antibody concentration correlated, but in2 patients there was no clear correlation, because 1 patient improved despite increasing antibody concentration and 1 patient did hot improve despite a lowered antibody concentration. It is possible that mechanisms other than anti-peripheral-nerve myelin antibodies may contribute to the effect of treatment.

In summary, it emerged that polyneuropathy is common in monoclonal gammopathy and that the method used to uncover an M-component is important. Both B cell and T cell responses may be involved in the pathogenesis, and a genetic susceptibility to develop polyneuropathy is possible. It is important to establish the diagnosis in these patients because immunosuppressive treatment may prove useful in some cases.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 1994. , 80 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 409
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-28083Local ID: 12848ISBN: 91-7871-251-3OAI: diva2:248634
Public defence
1994-02-04, Administrationsbyggnadens aula, Universitetssjukhuset, Linköping, 09:00 (Swedish)

Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.

Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-10-17Bibliographically approved

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