AChR Ab Research Articles

Factors influencing the clinical type and course of myasthenia gravis

Myasthenia gravis is considered to be an autoimmune disease in which several factors reciprocally influence the clinical type and course. We investigated the relative importance of the following factors: anti-acetylcholine receptor antibody (AChR Ab), HLA, age at onset, autoimmunity, thymic abnormality, duration of treatment, change in AChR Ab titer and immunosuppressive therapy. The pretreatment-AChR Ab titer and HLA were shown to significantly influence the clinical type. On the other hand, the age at onset significantly influenced the clinical course. The finding that with an onset at less than 5-year-old there was a tendency for a good prognosis suggests an association between the immaturity of the muscle and immune systems, and the clinical course.

Intrathecal synthesis of AChR Ab may cause pyramidal sign

Intrathecal synthesis of AChR Ab may cause pyramidal sign

Differences between ocular and generalized myasthenia gravis: binding characteristics of anti-acetylcholine receptor antibody against bovine muscles

We studied the binding characteristics of anti-acetylcholine receptor antibody (AChR Ab) in sera of nine patients with myasthenia gravis (MG) using affinity-purified extraocular muscles (EOM) and foot muscles (FM) of bovine species. The titer of AChR Ab measured with EOM was the same as that measured with FM for both ocular and generalized MG. In patients with ocular MG, the affinity of AChR Ab, determined by Scatchard analysis, was higher for FM than for EOM ( P < 0.05), whereas it was the same for EOM and FM in those with generalized MG. On the other hand, the affinity of AChR Ab for FM was lower in generalized MG than in ocular MG ( P < 0.05), but that for EOM did not differ between the two types of MG. The affinity of AChR Ab did not change after passing the patients' sera through an EOM-affinity column. The EOM-affinity column treatment of the sera decreased the AChR Ab titer measured with EOM in all patients, but the AChR Ab titer measured with FM was decreased in only some of the patients. These data indicate that there are polyclonal or heterogenous AChR Abs in the sera of MG patients, which does not help to explain the clinical difference between ocular and generalized MG.

Antibody production by blood lymphocytes in myasthenia gravis: reduction in disease of long duration.

We measured acetylcholine receptor antibody (AchR Ab) and IgG secreted in vitro by blood lymphocytes from myasthenia gravis patients and controls. Eleven of 20 patients secreted AchR Ab. Controls did not secrete AchR Ab. IgG secretion was lower in patients who were nonsecretors of AchR Ab (351 +/- 127 ng/ml/10 days) than in secretors (3,563 +/- 949) and both groups differed from controls (1,305 +/- 353). Absence of secretion of AchR Ab and low IgG secretion correlated with long disease duration. The data suggest that nonspecific suppression of B cell mediated immune function may occur in long-standing myasthenia gravis.

Involvement of HLA in clinical courses of myasthenia gravis

The relationship between the histocompatibility leukocyte antigen (HLA) phenotypes and the clinical course of myasthenia gravis (MG) was studied in 53 Japanese patients with MG. The frequency of HLA-DRw9 antigen was high in the MG patients who did not need immunosuppressive therapy but only anticholinesterase agents ( RR = 4.52; CP < 0.02), who achieved remission of the disease ( RR = 2.98; CP < 0.05) or two showed a decrease in AChR antibody (Ab) titer ( RR = 6.32; CP < 0.0002) whereas the frequency of HLA-DRw8 antigen was increased in MG patients who underwent immunosuppressive therapy ( RR = 4.03; CP < 0.01), who did not have remission ( RR = 4.75; CP < 0.1) or who showed an increase in AChR Ab titer ( RR = 6.48; CP < 0.01). These data suggest that immunogenetic heterogeneity in MG might be reflected in its clinical course.

Heterogeneity in myasthenia gravis: HLA phenotypes and autoantibody responses in ocular and generalized types.

HLA phenotypes and autoantibody responses were studied in 71 Japanese patients with myasthenia gravis. HLA-A2, Bw61, and DRw9 were associated with ocular myasthenia gravis (corrected p [CP] less than 0.05 relative risk [RR] = 2.88; CP less than 0.02, RR = 3.60; and CP less than 0.001, RR = 4.63, respectively) and HLA-DRw8 was associated with generalized myasthenia gravis (CP less than 0.001, RR = 5.40). Neither HLA-B8 nor DR3 was found in Japanese patients. The titer of antiacetylcholine receptor antibody (AChR Ab) and the incidence of autoantibodies other than AChR Ab were higher in patients with generalized myasthenia gravis than in those with the ocular type (2.77 +/- 0.62 versus 0.17 +/- 0.03 pmol/ml, p less than 0.001; and 60.6 versus 29.0%, p less than 0.02, respectively). Patients with a high titer of AChR Ab or with autoantibodies had an increased frequency of HLA-DRw8 (CP less than 0.02, RR = 4.61, and CP less than 0.005, RR = 4.53, respectively); whereas patients with a low titer of AChR Ab or without autoantibodies had an increased frequency of HLA-DRw9 (CP less than 0.001, RR = 8.26, and CP less than 0.005, RR = 4.08, respectively). These findings suggest that ocular and generalized myasthenia gravis might have different immunogenetic backgrounds.

Humoral immunity in myasthenia gravis: clinical correlations of anti-receptor antibody avidity and titer.

Antibody to human acetylcholine receptor (AChR Ab) in myasthenia gravis (MG) correlates with clinical (Osserman) classification. Patients in remission R) or with ocular only (I) symptoms differed significantly from those with generalized disease (IIA, IIB, III, IV) (p less than 0.01, p less than 0.05 respectively). Patients with mild generalized disease (IIA) differed significantly from those with acute severe (III) or chronic severe (IV) disease (p less than 0.01). However, within each clinical class titers ranged over two or three orders of magnitude. This variation in AChR Ab titer for patients with similar diseases severity was not explained by differences in immunoglobulin class. All patients produced IgG AChR Ab and occasional patients produced IgM or IgA at less than 10% of their IgG titer. No IgM to IgG switch was identified. In MG patients negative for AChR Ab by immunoprecipitation assay, blockade of toxin binding to extracted human AChR could still be identified indicating antibody specificity to the toxin binding site. The avidity of AChR Ab for receptor assayed in six myasthenic patients with differing severities of disease, varied widely with T1/2 (time to half-maximal binding) ranges from 25 to 81 minutes. However, differences in AChR Ab avidity did not explain differences in severity of disease in patients with similar titers. AChR Ab was fractionated in six patients into IgG kappa and IgG lambda; in four patients AChR Ab activity could be demonstrated in both fractions. Thus, differences among MG patients as a group are due to production of several AChR Ab idiotypes, with individual patients being oligoclonal or polyclonal as well. Differences in IgG subclass (complement fixation) and site of attachment of AChR Ab to receptor subunits may resolve these differences.

Acetylcholine receptor antibodies in myasthenia gravis.

A multivariate statistical analysis of levels of serum acetylcholine receptor antibody (AChR Ab) obtained from 197 patients with various clinical forms of myasthenia gravis (MG) was performed. Elevated AChR Ab levels are specific for MG, but normal AChR Ab levels do not rule out MG. Patients in remission or with purely ocular MG had the lowest incidence of elevation of serum AChR Ab levels, while patients with generalized, severe MG, particularly in the presence of thymoma, tended to have the greatest antibody elevations. Corticosteroids depressed AChR Ab levels, but thymectomy did not exert a consistent effect on antibody levels within a 24- to 30-month postoperative period. The relatively low 55% positivity of antibody elevations in all 197 patients probably reflects the use of heterologous (rat) AChR.