Clinical implementation of anti-acetylcholine receptor antibodies

Abstract

A multivariate analysis of anti-acetylcholine receptor (AChR) antibodies and clinical parameters other than treatment (modified Osserman groups, age, type of onset, sex, and thymus pathology) was performed for all incident (n = 366) myasthenia gravis (MG) cases in its white population in Denmark during the past 15 years. Sera from 244 healthy individuals and from 295 patients with diseases other than MG were analysed as controls. Formal statistics for the anti-AChR antibodies assay (immunoprecipitation RIA using crude human AChR extract) were calculated. The distribution of antibodies titres greater than 0.1 nMole/l was found to be approximately lognormal. For MG patients the 95% reference interval was 0.2-1549 nMoles/l, and in control sera the range was 0.0-0.4 nMole/l. Using 0.5 nMole/l as the cut-off level and regarding all results less than this value as normal titres, it appeared that the assay was highly specific (> 99.99%) for MG. In a population of MG patients significance should be attributed to values in the range 0.3-0.4 nMole/l. The overall diagnostic sensitivity was found to be 88%. The sensitivity appeared to be proportionate to clinical severity of MG. The percentage with a normal titre was higher (16%) for early onset of MG, compared with 7% for late onset. No significant difference in relation to the frequency of "negative titre" was found in relation to sex. Anti-AChR antibodies titre was found to correlate with clinical severity, female or male gender, and pathology of thymus. The groups of MG patients were not matched for the various clinical parameters but multiple regression analysis controlling for these variables revealed independent effects of clinical severity and sex though not of age. Normal thymus (including involuted gland) and thymoma were correlated with low to intermediate tires, and hyperplastic thymus with high level of antibodies. The clinical implementation of anti-AchR antibodies is reviewed from 1976 and up to the present. The problems with false positive results are thoroughly expounded.