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Diisocyanates are potent inducers of airways disease. Methylenediphenyl diisocyanate (MDI) is a widely used diisocyanate in the chemical industry. The aim of this study was to identify major and also immunologically relevant protein conjugates of MDI in plasma. Plasma was obtained from an MDI-exposed worker. The plasma was dialysed and then fractionated using ion exchange chromatography (IEC) and gel filtration. These fractions and also aliquots of unfractioned plasma were hydrolysed, derivatised and analysed for isocyanate adduct content using gas chromatography-mass spectrometry. In addition, immunologically relevant proteins were identified through specific IgG immunoblotting using pooled sera from two exposed workers. It was shown by dialysis that 96% of the hydrolysed MDI derivatives were protein bound and that 95% of the MDI adducts co-eluted with serum albumin in plasma using IEC. All MDI-protein adducts co-eluted with serum albumin using gel filtration. IgG immunoblotting showed a major 66 kDa protein and also some intermolecular reactions in serum albumin. This study shows serum albumin to be the major protein in plasma that forms adducts in vivo with MDI. Thus, a quick and simple quantitative method for biological monitoring may be developed for MDI exposure. The results also showed that MDI-specific IgG antibodies preferentially bind to the serum albumin in in-vitro-synthesised MDI-plasma protein conjugates.

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ABSTRACT. Ludvigsson, J., Johannesson, G., Heding, L., Häger, A. and Larsson, Y. (Departments of Paediatrics and Neurophysiology, University Hospital Linköping, Sweden and Novo Research Institute, Bagsvaerd, Denmark). Sensory nerve conduction velocity and vibratory sensibility in juvenile diabetics. Relationship to endogenous insulin. Acta Paediatr Scand, 68: 739, 1979.—Sensory nerve conduction velocity (NCV) and the vibratory sense (biothesiometry) were determined in 67 children and adolescents with insulin dependent diabetes. Age at onset of diabetes varied between 1–14 years (mean ±S.D. 6.5±3.6) and the duration of diabetes between 4–17 years (7.7±3.4). Within ±3 months of the nerve function tests blood was drawn for determination of C‐peptide and insulin antibodies (IgG and IRI). A low NCV (<50 m/s) in the sural nerve and/or an abnormal vibratory sense (≥1.0 microns) were found in 34 patients (50.7%). Measurable fasting serum C‐peptide 0.04–0.60 pmol/ml (0.17±0.15) was found in 16 patients (23.9%). All but one patients had insulin antibodies with IgG 0.130–11.029 mU/ml (2.957±2.509) and total IRI 10–9120 μU/ml (1204±1723). In multiple regression analysis we did not find any correlation between nerve function and sex, age, or age at onset of diabetes, and there was only a weak relationship between NCV and duration. However, there was a positive correlation between NCV and C‐peptide (p<0.001). Vibration sense was also better among patients with C‐peptide (p<0.05). The results support the view that insulin deficiency contributes to peripheral diabetic neuropathy.

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