Novel Molecular Biomarkers at the Blood-Brain Barrier in ALS
Out of 50 patients with sporadic amyotrophic lateral sclerosis (sALS), excluding 8 patients with recent immunosuppressive medication or low total IgG, we examined all available 92 sera of 11 women and 31 men nephelometrically for serum immunoglobulin concentrations including IgG isotypes IgG1-4. Mean serum levels of IgA and IgM remained within references in all cases. Isotypes IgG1 and IgG3 were the most frequently altered immunoglobulins. Without specific treatment, 34 out of 42 patients (= 80%) and 58 out of 92 sera (= 63%) demonstrated low IgG3 concentrations (< 0.41 g/l), while 14 patients (= 33%) and 20 sera (= 22%) demonstrated low IgG1 serum levels (< 4.22 g/l). In patients with normal total IgG, isotypes IgG1 and IgG2 often changed in a complementary way, and IgG1/IgG2 serum concentrations correlated significantly (rs = -0.518, P < 0.001). In four longitudinally monitored patients, the IgG3 isotype ranged from 1.3% to 8.2% of serum IgG and demonstrated a remarkable individual variability over time, corresponding to the relatively short half-life of IgG3. Since elevated circulating immune complexes may fluctuate rapidly, altered serum immunoglobulin isotypes could become more convenient parameters in a still enigmatic disease. To assess their role and relevance, their association with clinical course, cerebrospinal fluid and circulating immune complexes has to be examined.