Acetylcholine Receptor Antibody Titers Research Articles

High-dose intravenous immunoglobulin in the management of myasthenia gravis

Intravenous immunoglobulin, 400 mg/kg, was administered daily for five days to 12 patients with exacerbation of generalized myasthenia gravis. Degree of weakness, duration of illness, use of prednisone, and history of thymectomy or thymoma did not affect the response to intravenous immunoglobulin. Eleven patients improved, beginning 3.6 +/- 2.7 (mean +/- SD) days after the start of treatment and becoming maximal in 8.6 +/- 4.6 days, with sustained improvement lasting 52 +/- 37 days. Vital capacity increased from 1748 +/- 510 to 2700 +/- 614 mL at peak effect. Decreases in strength occurred in four patients beginning on day 3.2 +/- 2.5, lasted 1.5 +/- 0.6 days, and were mild in three patients. Other effects were minimal. There was no significant change in acetylcholine receptor antibody titers, which were elevated in all patients. Immunoglobulin seemed to produce a more rapid improvement than corticosteroids and is recommended as an adjunct in the management of myasthenia gravis exacerbations.

Effect of sera from myasthenia gravis patients on acetylcholine receptors in myotube cultures

Accelerated degradation of acetylcholine receptor (AChR) by antibody has been implicated in the loss of receptor sites in myasthenia gravis (MG). Our clinical and experimental data question the relevance of junctional AChR turnover in in vitro systems to the destruction of junctional human AChR sites in vivo. During the past 4 years, we have treated MG by early thymectomy, without employing other treatment modalities when possible, particularly anticholinesterase drugs and corticosteroids. Serial AChR antibody titers were determined before (n = 93) and after (n = 12) thymectomy. There was no significant difference in AChR antibody titer in the pre- versus post-thymectomy sera ( P > 0.1), while all patients improved clinically. The residual fraction of AChRs in pre-thymectomy MG patients were significantly different ( P < 0.001) from control values. Linear regression analysis of log e AChR destruction on log e AChR antibody level in pre-thymectomy patients was highly significant ( P ⪡ 0.01), with r 2 = 0.44, thus indicating that a large portion of the variation of AChR destruction can be accounted for by the AChR antibody level. The residual fraction of AChRs in pre- and post-thymectomy sera were not significantly different from one another ( P > 0.1), despite clinical improvement in all patients. Although there is a significant relationship between antibody titer and decreased residual fraction of AChRs in tissue culture, the relationship between these in vitro measurements and the clinical state of the patients is questionable. All our patients improved clinically post-thymectomy but their sera showed no significant difference in ability to decrease residual extrajunctional myotube AChRs. We suggest that the myotube AChR data reflect primarily an in vitro phenomenon and may not be the principal mechanism of AChR destruction in human MG.

A prospective study of thymectomy and serum acetylcholine receptor antibodies in myasthenia gravis.

Forty-seven consecutively presenting myasthenia gravis (MG) patients with generalized weakness were treated according to a standardized prospective protocol. All patients underwent a sternal splitting "total" thymectomy. Medical status before surgery was optimized by plasmapheresis without immunosuppression. Medications were avoided or discontinued whenever possible. All patients were improved. At the time of latest follow-up 83% were free of generalized weakness and 61% were on no medications. There was no significant change in Acetylcholine Receptor Antibody (AChR-AB) titer. The following conclusions were made: (1) thymectomy is an effective therapy for MG, (2) additional medications are not necessary in the majority of patients, and (3) a reduction in the AChR-AB titer is not essential for clinical benefit.

Thymectomy in late-onset myasthenia gravis.

Between 1977 and 1979, 12 consecutive patients with myasthenia gravis who were over the age of 55 years were treated by thymectomy. In all, their conditions improved clinically; 11 of the 12 became free of the generalized features of myasthenia gravis. Nine patients required no further medication. Acetylcholine-receptor antibody titers did not change significantly. Although five patients had atrophic thymus glands, their conditions also improved. We conclude that (1) thymectomy is a safe and effective therapy for patients with myasthenia gravis who are over the age of 55 years; (2) steroids and anticholinesterase agents are not essential in the management of late-onset myasthenia gravis; and (3) reduction in acetylcholine-receptor antibody titer is not essential for beneficial clinical response.

Acetylcholine receptor antibody titer and HLA-B8 antigen in myasthenia gravis.

In 82 white patients with myasthenia gravis, a high serum human acetylcholine receptor (AChR) antibody titer was related to the presence of the HLA-B8 antigen and increasing severity of the disease and not to age at onset, sex, presence of thymoma, or mode of treatment. Among patients without thymomas a high antibody titer was also associated with HLA-B8, particularly in those patients whose age at onset was less than 35 years. Thymectomy was associated with a lower median antibody titer when compared in two groups of HLA-B8-positive patients without thymoma who were similar for all other factors. Patients with thymomas who had received corticosteroids had a lower median titer than those who had not received steroids. This study supports the possibility that immune-response genes near the HLA-B8 segment of the major histocompatibility complex participate in the regulation of the humoral response to autoantigens, such as AChR protein.

Patterns of acetylcholine receptor antibody fluctuation in myasthenia gravis.

Serial acetylcholine receptor antibody (AChR-ab) titers have been followed in 32 patients with myasthenia gravis (MG) for an average of 43 months (range 12-81 months). Seventeen patients became asymptomatic or markedly improved during the study, 12 of whom showed AChR-ab decreases of greater than 50% sustained for 12 months. Only three of 15 patients showing no substantial clinical improvement had AChR-ab decreases greater than 50%. Steroids were more often associated with AChR-ab suppression than was thymectomy. The differences in AChR-ab suppressibility among identically treated patients were not predictable by any clinical characteristics studied. The study indicates a strong relationship between clinical course and AChR-ab in the individual patient when sustained improvement over 12 months and AChR-ab decreases greater than 50% are examined.

Gm ALLOTYPES IN MYASTHENIA GRAVIS

Gm typing and acetylcholine receptor antibody assay were performed on serum samples from 74 patients with myasthenia gravis (31 male, 43 female) and from 236 unrelated normal blood-donors. The haplotype Gm1,2,21 was significantly more common in patients with myasthenia gravis (relative risk=3-24), especially those with thymoma (relative risk=6·99). The frequency of haplotype Gm1,2,21 was further increased in patients with severe generalised myasthenia gravis (relative risk=10-52). The frequency of Gm1,2,21 was also increased in patients with high acetylcholine receptor antibody titres (>5 pmol/ml). The results indicate the presence of a pathogenic gene close to the IgG heavy-chain gene complex in the 6th chromosome in the patients with myasthenia gravis, especially those with thymoma.