Determination of IgG subclasses and Gm allotypes in culture supernatants of pokeweed mitogen-stimulated human blood lymphocytes.

Concentrations of the 4 IgG subclasses, of IgM, and of IgA were determined in culture supernatants of pokeweed mitogen-stimulated mononuclear cells isolated from human peripheral blood. Time-course studies showed cumulative secretion of IgM, IgA, and the subclasses IgG1, IgG2, and IgG3 but not of IgG4. In supernatants of 7-day cultures of unseparated mononuclear cells, IgG1 was predominant, followed by IgG2 and IgG3. Removal of most monocytes from the mononuclear cells resulted in an overall decrease of immunoglobulin production but had no influence on the relative IgG subclass distribution. In supernatants of T cell-enriched cultures, the synthesized IgG was deficient in IgG1. Likewise, in supernatants of B cell-enriched cultures, IgG2 exceeded IgG1 concentration. Elimination of the T gamma cells suggested some influence of this subset on IgG2 production. Gm allotypes determined in supernatants corresponded to those in serum of the blood donors.

Disproportionate elevation of the immunoglobulin G1 concentration in cerebrospinal fluids of patients with multiple sclerosis.

We determined immunoglobulin G (IgG) subclass concentrations and studied their distributions in the cerebrospinal fluids of patients suffering from multiple sclerosis, other inflammatory neurological diseases, and non-inflammatory diseases of the nervous system in comparison with a control group. In addition, the four subclass concentrations were measured in serum specimens of the multiple sclerosis and control groups. These data were correlated with the extent of local IgG synthesis in the subarachnoid spaces of the patients belonging to the different groups. We found a selective elevation of the IgG1 subclass in the cerebrospinal fluids of multiple sclerosis patients, and there was only a very small overlap of the IgG1 ranges of the multiple sclerosis and control groups. No major differences were detected between the IgG subclass distributions in different courses of multiple sclerosis nor between multiple sclerosis and control sera. The group with non-inflammatory diseases showed a uniform elevation of all four subclasses and a greater overlap with the normal range. This latter feature was combined with an elevated IgG1 concentration in the group with other inflammatory diseases. It is concluded that locally synthesized IgG in the cerebrospinal fluids of multiple sclerosis patients consists mainly of IgG1.

Determination of IgG subgroups in cerebrospinal fluid of multiple sclerosis patients and others.

IgG subgroups (IgG1, IgG2, IgG3, IgG4) were determined by radioimmunoassay (RIA) in cerebrospinal fluid (CSF) of controls, multiple sclerosis (MS), infectious diseases (ID) and other neurological diseases (OND). The proportion of IgG1 in the total IgG subgroup concentration was significantly higher in the MS group compared to the other groups while the IgG2 proportion was significantly lower; IgG3 and IgG4 did not show any consistent change. The inverse relationship between IgG1 and IgG2 was similar in all diagnostic groups: high concentration of IgG1 was associated with low concentrations of IgG2 and vice versa. Patients with a high relative concentration of IgG1 in their CSF have a seven to eight times higher statistical risk to be suffering from MS than ID or OND. In the MS group only the IgG1 concentration correlated with the total IgG concentration determined by radial immunodiffusion, while in controls, ID and OND each IgG subgroup correlated significantly with the IgG concentration. This demonstrates that in MS a selective increase of IgG1 subgroup is mainly responsible for the increase of total IgG, while all subgroups are involved in OND and ID showing an increased total IgG concentration.