CLINICAL IMPLEMENTATION OF ANTIACETYLCHOLINE RECEPTOR ANTIBODIES

A multivariate analysis of anti-acetylcholine receptor (AChR) antibodi es and clinical parameters other than treatment (modified Osserman gro ups, age, type of onset, sex, and thymus pathology) was performed for all incident (n = 366) myasthenia gravis (MG) cases in its white popul ation in Denmark during the past 15 years. Sera from 244 healthy indiv iduals and from 295 patients with diseases other than MG were analysed as controls. Formal statistics for the anti-AChR antibodies assay (im munoprecipitation RIA using crude human AChR extract) were calculated. The distribution of antibodies titres greater than 0.1 nMole/l was fo und to be approximately lognormal. For MG patients the 95% reference i nterval 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 r esults less than this value as normal titres, it appeared that the ass ay was highly specific (>99.99%) for MG. In a population of MG patient s significance should be attributed to values in the range 0.3-0.4 nMo le/l. The overall diagnostic sensitivity was found to be 88%. The sens itivity appeared to be proportionate to clinical severity of MG. The p ercentage 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 severi ty, female or male gender, and pathology of thymus. The groups of MG p atients were not matched for the various clinical parameters but multi ple regression analysis controlling for these variables revealed indep endent effects of clinical severity and sex though not of age. Normal thymus (including involuted gland) and thymoma were correlated with lo w to intermediate titres, and hyperplastic thymus with high level of a ntibodies. The clinical implementation of anti-AChR antibodies is revi ewed from 1976 and up to the present. The problems with false positive results are thoroughly expounded.